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*

Objective To investigate the therapeutic mechanism of Dingkun Dan(DKD)in polycystic ovary syndrome(PCOS)by examining the effects of microRNA-30d-5p on ovarian granulosa cells(GCs).Methods A PCOS rat model was established using dehydroepiandrosterone(DHEA).Normal rat GCs and PCOS rat GCs were cultured in vitro and divided into four groups:blank control group,model group,low-dose DKD group,and high-dose DKD group.After grouping,GCs viability was assessed using the methyl thiazolyl tetrazolium(MTT)assay,GCs apoptosis was analyzed by flow cytometry,and the gene expression of transforming growth factor β1(TGF-β1),Smad2,Smad3,and microRNA-30d-5p in GCs was measured by real-time polymerase chain reaction(RT-PCR),protein expression of TGF-β1,Smad2,and Smad3 in GCs was detected by Western Blot.Results Compared with the blank control group,the model group exhibited significantly decreased GCs viability,increased GCs apoptosis,upregulated mRNA and protein expression of TGF-β1,Smad2,and Smad3,and downregulated microRNA-30d-5p expression,the differences were statistically significant(P＜0.01).Compared with the model group,both low-and high-dose DKD groups showed increased GCs viability,reduced GCs apoptosis,downregulated mRNA and protein levels of TGF-β1 Smad2 and Smad3,elevated microRNA-30d-5p expression,and the differences were statistically significant(P＜0.05 or P＜0.01).Conclusion DKD promotes GCs proliferation by targeting Smad2 via microRNA-30d-5p,suggesting a potential therapeutic role in PCOS-related ovulatory dysfunction.

Objective To develop a nomogram model based on the nucleotide-binding oligomer-ization domain-like receptor protein 3(NLRP3)/caspase-1 signaling pathway to predict the value of secondary vascular dementia(VaD)after acute cerebral infarction(ACI)following thrombolytic ther-apy.Methods A total of 289 patients with ACI admitted to Yuncheng Central Hospital Affiliated to Shanxi Medical University from March 2021 to March 2024 were selected as study subjects,and were divided into VaD group(n=60)and non-VaD group(n=229)based on the occurrence of VaD.Rele-vant clinical data were compared between the two groups,and influencing factors for secondary VaD af-ter ACI were analyzed.A nomogram prediction model was constructed and validated.Results The proportions of patients with a history of smoking,hypertension and coronary heart disease,infarction in key areas,responsible large vessel stenosis ≥50％,leukoaraiosis,and thrombolysis benefit were higher in the VaD group than in the non-VaD group(P＜0.05).Logistic regression analysis showed that the degree of responsible vessel stenosis,infarctionin key areas,leukoaraiosis,and the expression of NLRP3,apoptosis-associated speck-like protein containing a CARD(ASC),and caspase-1,which are related to the NLRP3/caspase-1 signaling pathway,were independent influencing factors for sec-ondary VaD after ACI(P＜0.05).Receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DCA)indicated that the nomogram model had high discrimina-tion and predictive efficacy,with significant positive net benefit.Conclusion The independent in-fluencing factors for secondary VaD after ACI include the degree of responsible vessel stenosis,in-farction in key areas,leukoaraiosis,and the expression of NLRP3,ASC,and caspase-1 related to the NLRP3/caspase-1 signaling pathway.The nomogram prediction model established based on these indicators has high predictive value and clinical efficacy.

ObjectiveTo investigate the effects of Linggui Zhugantang （LGZGT）-containing serum on primary astrocytes （AS） induced by β amyloid 1-42 （Aβ_1-42） in a rat model of Alzheimer's disease （AD） and explore the phagocytic and degradative effects of LGZGT on Aβ. MethodAn AD model was established by inducing AS with Aβ_1-42. The cells were divided into normal group， model group， LGZGT low-， medium-， and high-dose （LGZGT-L， LGZGT-M， and LGZGT-H） groups， and donepezil hydrochloride group. The model group was treated with Aβ_1-42 at a final concentration of 10 μmol∙L^-1. The LGZGT-L， LGZGT-M， and LGZGT-H groups were treated with 10% serum containing LGZGT on the basis of the model group. Cell viability was assessed using a cell counting kit-8 （CCK-8）， lactate dehydrogenase （LDH） activity was measured using an LDH assay kit， and cell morphology was observed using an inverted microscope. The expression of Aβ-related degradation enzymes insulin-degrading enzyme （IDE） and cathepsin D （CTSD） was detected using Western blot， and the fluorescence intensity of cathepsin B （CTSB） was measured using immunofluorescence. The content of Aβ_1-42 in cells was determined using an enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the normal group， the viability of AS in all groups decreased， and Aβ_1-42 at different concentrations had inhibitory effects on AS proliferation. After administration， compared with the normal group， the cell survival rate of the model group decreased significantly （P<0.05）. Compared with the model group， the cell survival rates of the LGZGT-H group and donepezil hydrochloride group increased significantly （P<0.05）. The LDH activity of cells in the model group was significantly increased compared with that in the normal group （P<0.05）， and cell bodies were swollen and enlarged with increased protrusions and elongation， suggesting more obvious cell damage. Compared with the model group， the LDH activity of cells in the donepezil hydrochloride， LGZGT-L， LGZGT-M， and LGZGT-H groups decreased significantly （P<0.05）. After administration， the cell swelling in the LGZGT-M， LGZGT-H， and donepezil hydrochloride groups improved， cell protrusions shortened， and cell clustering decreased. Compared with the normal group， the expression of IDE and CTSD in the model group decreased significantly （P<0.05）. Compared with the model group， the expression of IDE increased significantly in the LGZGT-M and LGZGT-H groups （P<0.05）. Compared with the model group， the expression of CTSD increased significantly in the LGZGT-L， LGZGT-M， LGZGT-H， and donepezil hydrochloride groups （P<0.05）. The average fluorescence intensity of CTSB in the model group was significantly lower than that in the normal group （P<0.05）. Compared with the model group， the average fluorescence intensity of CTSD in the LGZGT-L， LGZGT-M， LGZGT-H， and donepezil hydrochloride groups increased significantly （P<0.05）. The intracellular content of Aβ_1-42 in cells in the model group was significantly higher than that in the normal group （P<0.05）. After administration， compared with the model group， the intracellular content of Aβ_1-42 in cells in the LGZGT-L， LGZGT-M， LGZGT-H， and donepezil hydrochloride groups decreased significantly （P<0.05）， and LGZGT-containing serum reduced Aβ_1-42 in a dose-dependent manner （P<0.05）. ConclusionLGZGT has a protective effect on Aβ_1-42-induced AS and can promote the degradation of Aβ. Its mechanism may be related to reducing Aβ toxicity， enhancing cell viability， promoting the expression of IDE， CTSD， and CTSB， and restoring lysosomal function.

ObjectiveTo observe the clinical efficacy of modified Yigongsan combined with multi-enzyme tablets and bifidobacterium triple live powder on infantile anorexia with spleen-stomach Qi deficiency syndrome. MethodA total of 112 infantile patients anorexia with spleen-stomach Qi deficiency syndrome treated at Hebei Provincial Hospital of Traditional Chinese Medicine from January 2022 to June 2023 were enrolled and divided into a control group and an observation group， with 56 cases in each group， according to a random number table. Children in the control group were treated with multi-enzyme tablets and Bifidobacterium triple live powder， while those in the observation group were treated with modified Yigongsan in addition to the treatment in the control group. During the study， one case dropped out in the control group and two cases dropped out in the observation group. The clinical efficacy of the two groups of children was compared， including changes in traditional Chinese medicine （TCM） syndrome scores （main symptoms， secondary symptoms， tongue， and pulse）， time to restore normal food intake， and increase in body weight. Changes in calcium， iron， zinc levels， hemoglobin， and albumin levels before and after treatment， as well as changes in gastrointestinal hormones such as gastrin and motilin， vasoactive intestinal peptide， somatostatin， neuropeptide Y， orexin， and leptin， were observed. The occurrence of adverse reactions in the two groups of children during the study was also recorded. ResultThe total effective rate of children in the control group after treatment was 85.19% （46/54）， while that in the observation group was 98.15% （53/54） （χ² =5.939， P<0.05）. Compared with the control group， the time for food intake to return to normal in the observation group was shorter， and the increase in body weight was greater （P<0.05）. Compared with the results before treatment， the TCM syndrome scores （main symptoms， secondary symptoms， tongue， and pulse） in both groups of children significantly decreased， while the levels of calcium， iron， zinc， hemoglobin， albumin， gastrin， motilin， neuropeptide Y， and orexin increased， and the levels of vasoactive intestinal peptide， somatostatin， and leptin decreased （P< 0.01）. Compared with the control group after treatment， the improvement in the above indicators in the observation group was more significant （P<0.01）. The incidence of adverse reactions in the two groups of children during the treatment period was similar， and the difference was not statistically significant. ConclusionModified Yigongsan combined with multi-enzyme tablets and Bifidobacterium triple live powder is highly effective in treating infantile anorexia （spleen-stomach Qi deficiency syndrome）. After treatment， symptoms of the children were improved，appetite and food intake increased， gastrointestinal function was improved， body weight increased， and adverse reactions were few， indicating that the treatment was safe and reliable.

Objective:To investigate the impact of the interval period between biopsy and MR examination on tumor detection and extraprostatic extension (EPE) assessment for prostate cancer (PCa) using multi-parametric MRI (mpMRI).Methods:The study was cross-sectional and retrospectively included 130 patients with PCa who underwent RP and preoperative systematic biopsies followed by mpMRI between January 2021 and December 2022 in the First Medical Center of Chinese PLA General Hospital. Patients were divided into 3 groups according to interval following biopsy (group A,<3 weeks, 31 cases; group B, 3-6 weeks, 67 cases; group C,>6 weeks, 32 cases). The percentages of hemorrhage volume in the total prostate were drawn on T 1WI and calculated. The junior, senior and expert radiologists independently localized the index lesions and calculated the accuracy for tumor detection, in addition to assessing the probabilities of EPE according to EPE grade. The correlation between the hemorrhage extent and interval was analyzed using the Spearman correlation coefficient. The accuracy for tumor detection was compared using χ2 test among groups. The diagnostic performance of the radiologists for EPE prediction was assessed using the receiver operating characteristic curve, and the differences between the corresponding area under the curve (AUC) were compared using the DeLong test. Results:The percentage of hemorrhage was correlated with the interval between biopsy and MR examination ( r=-0.325, P<0.001). The detection accuracy of junior radiologist was 83.9% (26/31), 76.1% (51/67), and 78.1% (25/32) in group A, B and C, respectively; no differences were observed in the detection accuracy among three groups ( χ2=0.76, P=0.685). The detection accuracy of senior radiologist was 83.9% (26/31), 80.6% (54/67), and 71.9% (23/32) in 3 groups with no differences ( χ2=1.53, P=0.464). The detection accuracy of expert radiologist was 80.6% (25/31), 77.6% (52/67), and 93.8% (30/32) with no differences ( χ2=3.95, P=0.139). The AUC (95% CI) for predicting EPE were 0.830 (0.652-0.940), 0.704 (0.580-0.809), 0.800 (0.621-0.920) in the group A, B and C for junior radiologist; 0.876 (0.708-0.966), 0.768 (0.659-0.863), 0.896 (0.736-0.975) for senior radiologist; and 0.866 (0.695-0.961), 0.813 (0.699-0.895), 0.852 (0.682-0.952) for expert radiologist, respectively. No differences were observed among the subgroups in each radiologist ( P>0.05). Conclusion:The interval period does not significantly affect the detection accuracy and EPE assessment of PCa using mpMRI. There is probably no necessity for prolonged intervals following systematic biopsy to preserve the clarity of MRI interpretation for PCa.

Objective:To investigate interleukin-37 (IL-37) expression in patients with diabetic kidney disease (DKD), and to assess the regulation of exogenous IL-37 on CD8 + T cell function in DKD patients. Methods:A cross-section study was carried out. Twenty healthy controls, thirty-six patients with diabetes mellitus type 2 (T2DM), and forty-seven DKD patients were enrolled in the study. Peripheral blood was collected. Plasma and peripheral blood mononuclear cells were isolated. IL-37 and soluble IL-1 receptor 8 (IL-1R8) levels in the plasma were measured by enzyme-linked immunosorbent assay (ELISA). IL-18 receptor α chain (IL-18Rα), IL-1R8 and immune checkpoint molecules levels in CD8 + T cells were measured by flow cytometry. CD8 + T cells were purified, and were stimulated with recombinant IL-37. CD8 + T cells were co-cultured with HEK293 cells in either direct contact or indirect contact manner. Levels of perforin, granzyme B, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were measured by ELISA. The proportion of target cell death was assessed by measuring lactate dehydrogenase level. Results:Plasma IL-37 levels in DKD patients [(63.42±23.30) ng/L] were significant lower than those in healthy controls [(143.02±50.67) ng/L] and T2DM patients [(87.88±40.62) ng/L] ( t=8.848, P<0.001; t=3.456, P<0.001). Plasma IL-37 level had good predictive values for T2DM in health individuals and for DKD in T2DM patients [the area under the curve was 0.797 (95% CI 0.676-0.917, P<0.001) and 0.691 (95% CI 0.576-0.807, P=0.003), respectively]. Plasma IL-37 level was negatively correlated with urea nitrogen ( r=-0.313, P=0.032) and creatinine ( r=-0.477, P<0.001), and positively correlated with estimated glomerular filtration rate (eGFR) ( r s=0.478, P<0.001) in DKD patients. IL-1R8 + CD8 + cell proportion in DKD patients (33.60%±9.47%) was significantly higher compared to healthy controls (16.29%±5.97%) and T2DM patients (17.13%±4.85%) ( t=7.545, 9.516, both P<0.001), but did not correlate with fast blood glucose, urea nitrogen, creatinine, or eGFR (all P>0.05). There were no statistical differences of IL-18Rα + CD8 + cell proportion, soluble IL-1R8 level, or immune checkpoint molecule proportion in CD8 + T cells among healthy controls, T2DM patients, and DKD patients (all P>0.05). Perforin and granzyme B secretions by CD8 + T cells were significantly elevated in DKD patients compared with healthy controls [(108.78±12.42) ng/L vs. (94.60±10.07) ng/L, t=3.096, P=0.005; (261.34±48.79) ng/L vs. (166.28±30.80) ng/L, t=3.387, P=0.002] and T2DM patients [(108.78±12.42) ng/L vs. (92.58±14.71) ng/L, t=3.263, P=0.003; (261.34±48.79) ng/L vs. (170.66±39.24) ng/L, t=2.627, P=0.014]. There were no significant differences of either IFN-γ or TNF-α secretions by CD8 + T cells among healthy controls, T2DM patients, and DKD patients (all P>0.05). In direct contact co-culture manner, CD8 + T cell-induced HEK293 cell death was down- regulated (13.03%±4.97% vs. 17.88%±5.19%, t=2.235, P=0.037). The levels of perforin [(222.02±25.79) ng/L vs. (294.30±25.58) ng/L, t=6.603, P<0.001], granzyme B [(416.27±90.24) ng/L vs. (524.71±115.53) ng/L, t=2.454, P=0.023], IFN-γ [(23.66±4.20) ng/L vs. (35.18±8.51) ng/L, t=4.026, P<0.001] and TNF-α [(1.62±0.29) μg/L vs. (2.09±0.57) μg/L, t=2.302, P=0.034] were also reduced as well. In indirect contact co-culture manner, there were no significant differences of CD8 + T cell-induced HEK293 cell death, perforin, or granzyme B levels between no stimulation and IL-37 stimulation (all P>0.05). IFN-γ and TNF-α levels in the supernatants were reduced in response to IL-37 stimulation [(23.56±6.24) ng/L vs. (32.56±9.90) ng/L, t=2.550, P=0.019; (1.41±0.31) μg/L vs. (2.10±0.44) μg/L, t=4.011, P<0.001]. Conclusion:IL-37 level is reduced in DKD patients.Exogenous IL-37 suppresses the cytotoxicity of CD8 + T cells in DKD patients.