Objective To quantitatively assess the exposure-response association between exposure to heatwave and sudden death, estimate the attributable excess deaths, and identify potential vulnerable subgroups. Methods A time-stratified case-crossover study was conducted among residents who died from sudden death in Jiangsu Province, China between 2015 and 2021. Heatwave events in Jiangsu Province, defined using varying relative temperature thresholds and durations, were identified using temperature data from the China Meteorological Administration Land Data Assimilation System (CLDAS V2.0). Individual heatwave exposure was assessed based on each subject's residential address. The exposure-response association between heatwave and sudden death was evaluated using conditional logistic regression model combined with a Distributed Lag Nonlinear Model(DLNM). Heatwave-attributable excess deaths were estimated. Stratified analyses by sex and age were performed to assess potential effect modifications. Results Under all definitions, exposure to heatwave was significantly associated with an increased risk of sudden death, and the risk increased with the intensity of heatwave. Using the P95_3d definition (temperature exceeding the 95th percentile for ≥3 consecutive days), heatwave was significantlyassociated with a 56% increased risk of sudden death (95% CI: 31%, 86%). The population-attributable fraction of sudden death due to heatwave exposure was 1.45% (95% CI: 0.97%, 1.90%). Stratified analyses indicated no statistically significant differences in the association between heatwave exposure and sudden death across age or sex subgroups. Conclusion Heatwave exposure was associated with an increased risk of sudden death. Reducing heatwave exposure during summer may help lower the occurrence of sudden death.

Objective: To prepare the erythrocyte-liposome drug delivery system to enhance the therapeutic effect of drugs on tumors and inhibit tumor metastasis. Methods: This study prepared and characterized paclitaxel (PTX)-plerixafor (AMD3100) liposomes (Lips), developed the erythrocyte-liposome drug delivery system, and evaluated its targeting efficiency and therapeutic efficacy through a series of in vitro cellular and in vivo animal experiments. Results: The particle size of PTX-AMD-Lips was (186.4±0.83) nm. Drug encapsulation efficiency of PTX-AMD-Lips was (75.50±5.27)% for PTX and (88.31±2.45)% for AMD. The Binding efficiency between RBC and liposomes in the drug delivery system was (69.93±2.55)%. Vitro cellular experiments revealed that PTX-AMD-Lips significantly inhibited tumor cell migration. In vivo animal experiments, the erythrocyte-liposome drug delivery system significantly increased drug accumulation in the lungs. At the experimental endpoint, the quantitative fluorescence signal of tumor size measured (4.04±0.44)×10 for the PTX-Lips group, and (5.14±3.40)×10 for the RBC-PTX-AMD-Lips group. Conclusion: The erythrocyte-liposome drug delivery system could enhance the lung-specific targeting capability of liposomes, kill tumor cells and suppress further metastasis effectively.

Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

Objective: To verify the inhibitory effect of a carbon monoxide hemoglobin-based oxygen carrier (CO-HBOC) on the fibrotic process in mice with idiopathic pulmonary fibrosis (IPF), clarify its efficacy difference compared with hemoglobin-based oxygen carriers (HBOCs), and elucidate its mechanism of action via proteomic analysis. Methods: CO-HBOC was prepared using gas loading technology. An IPF mouse model was established and the mice were randomly divided into a normal saline control group, an HBOC treatment group, and a CO-HBOC treatment group. The fibrotic area percentage was analyzed using Micro-CT; the degree of inflammatory infiltration and fibrosis in lung tissue was assessed by pathological section staining (e.g., HE and Masson staining); and differentially expressed proteins in lung tissue of IPF mice after CO-HBOC treatment were screened using proteomic technology. Results: Micro-CT results showed that the mean fibrotic area percentage in the CO-HBOC treatment group on day 21 was (8.89±0.98)%, which was better than that of the HBOC group (16.5±1.732)% and the normal saline group (30.75±6.45)% (P<0.05). HE and Masson staining results showed that the CO-HBOC group had reduced inflammatory cell infiltration and significantly decreased collagen fiber deposition in lung tissue, with a mean pathological score of 3.33±0.58, which was lower than that of the normal saline control group (8.33±1.53)(P<0.05); the mean collagen-positive area percentage was (3.33±1.53)%, significantly lower than that of the normal saline control group (14.00±3.61)% (P<0.05). Proteomic analysis identified 330 differentially expressed proteins, which were mainly enriched in inflammatory response regulatory pathways (such as the complement and coagulation cascades), and the expression changes of complement proteins may be the core target of CO-HBOC's anti-fibrotic effects. Conclusion: CO-HBOC can inhibit inflammatory responses and regulate fibrosis-related signaling pathways, there-by effectively inhibiting the fibrotic process in IPF mice, with superior efficacy to HBOC. Its mechanism of action involves the regulation of complement cascade-related signaling pathways and complement protein expression, providing an experimental and theoretical basis for targeted therapy of IPF.

Objective: To enhance the ability of nanoparticles to target and bind tumor cells by constructing a neutrophil hitchhiking system based on hyaluronic acid (HA)-modified dual-drug loaded lipid nanoparticles. Methods: Lipid nanoparticles (LNPs) were prepared using microfluidic technology, and the nitrogen/phosphate (N/P) ratio, flow rate ratio, and drug-to-lipid ratio were optimized. HA-modified LNPs (HA-LNPs) were prepared and characterized. The interaction between the nanoparticles and tumor cells was evaluated through in vitro cell experiments. Results: The optimal preparation conditions for LNPs are N/P=8, flow rate ratio=5, and drug-to-lipid ratio=1∶30 (w∶w). HA-LNPs has a particle size of (177.28±2.41) nm, a polydispersity index (PDI) of 0.198±0.10, and an siRNA encapsulation efficiency of (91.37±0.47)%. The optimal binding rate with neutrophils was (98.64±2.34)%. Conclusion: An HA-modified dual-drug loaded lipid nanoparticle-neutrophil hitchhiking system was successfully constructed, enhancing the synergistic anti-tumor activity of the nanomedicine and the uptake of nanoparticles by tumor cells, providing a novel delivery strategy for targeted therapy of bone marrow tumors.

BACKGROUND:Patellar tendonitis can present as tendon degeneration that fails to heal due to tissue overload and incomplete recovery.Patellar tendonitis is a predisposition to high jumping and its pathogenesis has not been clearly defined.OBJECTIVE:To explore the stress-strain relationship of patellar tendon in the take-off technique of high jump through the finite element model with accurate human anatomical structure,so as to provide ideas for the prevention and rehabilitation of patellar tendinitis.METHODS:Based on the CT and MRI imaging data of the lower extremity(including the knee and ankle)of one subject(22 years old,183 cm height,70 kg body mass),a three-dimensional finite element model of the lower extremity was reconstructed using medical imaging software,reverse engineering software and modeling software.The plantar pressure of the take-off leg was collected in eight subjects by gait testing system,and the technical action of high jump take-off was collected by motion capture system.The captured data were imported into human sports biomechanics software for analysis,and kinematic and kinetic data were obtained as the boundary conditions of finite element model for finite element simulation analysis.RESULTS AND CONCLUSION:The force borne by the patellar tendon reached 3.29 times of its own body mass when the subjects took off.In the take-off stage,the peak values of normal equivalent stress,strain and shear stress of the patellar tendon were 127.76 MPa,0.81 and 37.69 MPa,respectively,which were in the nonlinear region of the stress-strain curve,and the peak values were distributed in the proximal and posterior parts of patellar tendon.To conclude,the high patellar tendon force,strain and shear stress caused by the load of 3.29 times its own body mass during take-off are related to the induction of patellar tendinitis.

BACKGROUND:Patellar tendonitis can present as tendon degeneration that fails to heal due to tissue overload and incomplete recovery.Patellar tendonitis is a predisposition to high jumping and its pathogenesis has not been clearly defined.OBJECTIVE:To explore the stress-strain relationship of patellar tendon in the take-off technique of high jump through the finite element model with accurate human anatomical structure,so as to provide ideas for the prevention and rehabilitation of patellar tendinitis.METHODS:Based on the CT and MRI imaging data of the lower extremity(including the knee and ankle)of one subject(22 years old,183 cm height,70 kg body mass),a three-dimensional finite element model of the lower extremity was reconstructed using medical imaging software,reverse engineering software and modeling software.The plantar pressure of the take-off leg was collected in eight subjects by gait testing system,and the technical action of high jump take-off was collected by motion capture system.The captured data were imported into human sports biomechanics software for analysis,and kinematic and kinetic data were obtained as the boundary conditions of finite element model for finite element simulation analysis.RESULTS AND CONCLUSION:The force borne by the patellar tendon reached 3.29 times of its own body mass when the subjects took off.In the take-off stage,the peak values of normal equivalent stress,strain and shear stress of the patellar tendon were 127.76 MPa,0.81 and 37.69 MPa,respectively,which were in the nonlinear region of the stress-strain curve,and the peak values were distributed in the proximal and posterior parts of patellar tendon.To conclude,the high patellar tendon force,strain and shear stress caused by the load of 3.29 times its own body mass during take-off are related to the induction of patellar tendinitis.

Objective To investigate the infection with key intestinal parasites in the Jinuo-inhabited areas of Yunnan Province in 2023 and provide a scientific basis for preventing and controlling local parasitic diseases.Methods A cluster random sampling method was used to conduct a survey on human intestinal parasitic diseases in Jinuoshan Township,Jinghong City,Xishuangbanna Dai Autonomous Prefecture,Yunnan Province,from October to November 2023.Fecal samples and information on epidemiological factors were collected from permanent residents of the Jinuo ethnic group.Intestinal helminth eggs were detected and counted using the modified Kato-Katz technique(two slides per fecal sample).Intestinal protozoa were identified via iodine-stained smears.Each fecal sample was subjected to hookworm larval culture using the test tube filter paper method for species identification.Additionally,transparent adhesive tape anal swabs were used to detect Enterobius vermicularis eggs in children aged 3-9 years.Results A total of 1 367 individuals was examined,with 11 species of parasites detected,including 5 helminth species and 6 protozoan species.The overall intestinal parasite infection rate was 25.97%,with helminth and protozoan infection rates at 17.63%and 9.07%,respectively.The infection rate of E.vermicularis in children(via anal swabs)was 16.35%.The infection rates of specific parasites were as follows:Ascaris lumbricoides 0.07%,hookworm 13.97%,Trichuris sp.0.29%,Taenia solium 0.15%,Entamoeba nana 1.68%,Giardia lamblia 1.61%,Entamoeba histolytica 0.07%,Entamoeba coli 0.07%,Iodamolbe butschlii 1.61%,and Blastocystis hominis 4.10%.The degree of Acaris lumbricoides,hookworm,and Trichuris sp.infection was mainly mild.Hookworm species were identified as Necator americanus and Ancylostoma duodenale.No statistically significant differences in infection rates were observed across different village committees,genders,age groups,or occupations(P＞0.05).The infection rates of preschool children and illiterate people were higher at 82.61%and 67.02%,respectively(χ2=344.798,P＜0.01).The infection rate of the Jinuo people was 32.49%,which is higher than that of other ethnic groups(χ2=109.493,P＜0.01).Conclusions The prevalence of intestinal parasitic infections among the Jinuo ethnic group in Yunnan Province remains relatively high.Strengthened prevention and control measures targeting relevant populations are urgently needed,with a particular focus on hookworm infections and E.vermicularis infections in children.

Patients with periodontal disease often require combined periodontal-orthodontic interventions to restore periodontal health, function, and aesthetics, ensuring both patient satisfaction and long-term stability. Managing these patients involving orthodontic tooth movement can be particularly challenging due to compromised periodontal soft and hard tissues, especially in severe cases. Therefore, close collaboration between orthodontists and periodontists for comprehensive diagnosis and sequential treatment, along with diligent patient compliance throughout the entire process, is crucial for achieving favorable treatment outcomes. Moreover, long-term orthodontic retention and periodontal follow-up are essential to sustain treatment success. This expert consensus, informed by the latest clinical research and practical experience, addresses clinical considerations for orthodontic treatment of periodontal patients, delineating indications, objectives, procedures, and principles with the aim of providing clear and practical guidance for clinical practitioners.
Humans ; Consensus ; Orthodontics, Corrective/standards* ; Periodontal Diseases/complications* ; Tooth Movement Techniques/methods* ; Practice Guidelines as Topic

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*