ObjectiveTo explore the material basis of the "interaction of blood stasis and toxin" mechanism in cerebral ischemia-reperfusion injury， as well as the protective role of Huoxue Huayu Jiedu prescription （HXHYJDF） against ferroptosis. MethodsSixty SPF-grade male SD rats were randomly divided into six groups： sham group， model group， deferoxamine （DFO） group （100 mg·kg^-1）， low-dose HXHYJDF group （4.52 g·kg^-1）， medium-dose HXHYJDF group （9.04 g·kg^-1）， and high-dose HXHYJDF group （18.07 g·kg^-1）， with ten rats in each group. Except for the sham group， the other groups were used to replicate the model of focal cerebral ischemia-reperfusion in the middle cerebral artery of rats by the reforming Longa method. Neurological function was assessed at 1^st， 3^rd， 5^th， and 7^th days post-reperfusion using the modified neurological severity scores （m-NSS）. Brain tissue pathology and the morphology of mitochondria were observed using hematoxylin-eosin （HE） staining and transmission electron microscopy. The contents of malondialdehyde （MDA）， glutathione （GSH）， divalent iron ions （Fe²⁺）， and reactive oxygen species （ROS） in the ischemic cerebral tissue were detected using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot （WB） were used to detect the expression of iron death marker proteins glutathione peroxidase 4 （GPX4）， ferroportin-1 （FPN1）， transferrin receptor protein 1 （TfR1）， and ferritin mitochondrial （FtMt） in brain tissue. ResultsCompared with the sham group， the mNSS score of the model group was significantly increased （P<0.01）. HE staining showed that the number of neurons in the cortex of brain tissue was seriously reduced， and the intercellular space was widened. The nucleus was fragmented， and the cytoplasm was vacuolated. The results of transmission electron microscopy showed that the mitochondria in the cytoplasm contracted and rounded， and the mitochondrial cristae decreased. The matrix was lost and vacuolated， and the density of the mitochondrial bilayer membrane increased. The results of ELISA showed that the content of GSH decreased significantly （P<0.01）， and the contents of MDA， Fe²⁺， and ROS increased significantly （P<0.01）. The results of immunohistochemistry and WB showed that the expression of GPX4 and FPN1 proteins was significantly decreased （P<0.01）， and the expression of FtMt and TfR1 proteins was significantly increased （P<0.01）. Compared with those of the model group， the m-NSS scores of the high-dose and medium-dose HXHYJDF groups began to decrease on the 3^rd and 5^th days， respectively （P<0.05， P<0.01）. The results of HE and transmission electron microscopy showed that the intervention of HXHYJDF improved the pathological changes of neurons and mitochondria. The results of ELISA showed that the content of GSH in the medium-dose and high-dose HXHYJDF groups increased significantly （P<0.01）， and the contents of MDA， Fe²⁺， and ROS decreased significantly （P<0.05， P<0.01）. The content of GSH in the low-dose HXHYJDF group increased significantly （P<0.01）， and the contents of MDA and ROS decreased significantly （P<0.01）. The results of immunohistochemistry showed that the expression of GPX4 and FPN1 in the high-dose HXHYJDF group increased significantly （P<0.01）， and the expression of FtMt and TfR1 decreased significantly （P<0.01）. The expression of GPX4 and FPN1 in the medium-dose HXHYJDF group increased significantly （P<0.05）， and the expression of TfR1 decreased significantly （P<0.01）. WB results showed that the expression levels of FPN1 and GPX4 proteins in the high-dose， medium-dose， and low-dose HXHYJDF groups were significantly up-regulated （P<0.01）， and the expression levels of FtMt and TfR1 proteins were significantly down-regulated （P<0.01）. ConclusionHXHYJDF can significantly improve neurological dysfunction symptoms in rats with cerebral ischemia-reperfusion injury， improve the pathological morphology of the infarcted brain tissue， and protect the brain tissue of rats with cerebral ischemia-reperfusion injury to a certain extent. Neuronal ferroptosis is involved in cerebral ischemia-reperfusion injury， with increased levels of MDA， Fe²⁺， ROS， and TfR1 and decreased levels of FtMt， FPN1， GPX4， and GSH potentially constituting the material basis of the interaction of blood stasis and toxin mechanism in cerebral ischemia-reperfusion injury. HXHYJDF may exert brain-protective effects by regulating iron metabolism-related proteins， promoting the discharge of free iron， reducing brain iron deposition， alleviating oxidative stress， and inhibiting ferroptosis.

BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. Despite their therapeutic potential, the use of ADCs faces significant challenges, including off/on-target toxicity and resistance development. This review examines the current landscape of ADC development, focusing on the critical aspects of target selection and antibody engineering. We discuss strategies to increase ADC efficacy and safety, including multitarget approaches, pH-dependent antibodies, and masked peptide technologies. The importance of comprehensive antigen expression profiling in both tumor and normal tissues is emphasized, highlighting the role of advanced technologies, such as single-cell sequencing and artificial intelligence, in optimizing target selection. Furthermore, we explore combination therapies and innovations in linker‒payload chemistry, which may provide approaches for expanding the therapeutic window of ADCs. These advances pave the way for the development of more precise and effective cancer treatments, potentially extending ADC applications beyond oncology.
Humans ; Immunoconjugates/adverse effects* ; Neoplasms/immunology* ; Animals ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents/therapeutic use*

Tourette syndrome(TS)is a chronic neurodevelopmental disorder.Acupuncture can effectively improve the clinical symptoms of TS patients.This article systematically summarized the clinical research status of acupuncture for the treatment of TS in recent years from the aspects of characteristic acupuncture methods,characteristic needles and comprehensive therapies,and put forward suggestions and prospects for systematically elaborating the peripheral-central mechanism of acupuncture for TS around the intestinal immunity and brain network mechanism in the future,so as to provide reference for optimizing clinical research and treatment.

Sepsis is one of the common severe diseases caused by the dysregulated host response to infection， which seriously threatens the life and health of human beings all over the world. The incidence and mortality of the disease are extremely high， and it has always been an urgent problem to be solved in the field of acute and critical diseases. At present， anti-infection， fluid resuscitation， mechanical ventilation and other programs are most used in clinic to treat sepsis， but their poor prognosis and high cost and other issues remain to be resolved. Therefore， it is necessary to explore a new， efficient， safe and inexpensive drug and treatment model at this stage. The treatment of traditional Chinese medicine （TCM） is based on syndrome differentiation and holistic concept. It can effectively regulate the progression of sepsis， maintain the homeostasis of the body， and has fewer adverse reactions. It has achieved good clinical results. In recent years， a large number of studies have shown that TCM can reduce the inflammatory response by regulating the Toll-like receptor 4（TLR4） signaling pathway， thereby reducing the severity and mortality of sepsis patients. However， there is still a lack of systematic exposition of TCM regulating TLR4 signaling pathway in the treatment of sepsis. Therefore， this article summarizes the relationship between TLR4 signaling pathway and sepsis and the mechanism of TCM in the disease by searching and consulting relevant literature in recent years. It is found that some Chinese medicine monomers and active ingredients， Chinese medicine compounds and Chinese medicine preparations can effectively reduce systemic inflammatory response， repair organ damage and improve the prognosis of sepsis by inhibiting the activation of TLR4 signaling pathway. However， due to various limitations， some studies have directly focused on the differential expression and function of TLR4， ignoring the downstream molecular expression and phenotypic effects of TLR4. The alternative mechanism， relationship and specific molecular mechanism of the pathway are still unclear. There are problems such as unclear pharmacokinetics and unclear mechanism in the pro- and anti-inflammatory balance， which need to be further studied and explored in order to provide new ideas for the potential treatment and drug development for sepsis.

Objective To investigate the therapeutic effect of segmental decompression combined with corrective short-segment fusion surgery for the treatment of degenerative lumbar scoliosis.Methods In total,124 patients with degenerative lumbar scoliosis were selected and divided into short-and long-segment fusion groups using the random number table method,with 62 patients in each group.Posterior short-segment decompression,fixation,and fusion were performed in the short-segment fusion group;the fusion segment was the adjacent lumbar vertebra.Posterior long-segment decompression,fixation,and fusion were performed in the long-segment fusion group;the fusion segments included multiple adjacent lumbar vertebrae.At the 6th month after surgery,the coronal Cobb angle of lumbar convexity,sagittal Cobb angle of lumbar lordosis,intervertebral foramen height,intervertebral space height,intervertebral foramen area,spinal canal area,spinal canal diameter,Japanese Orthopedic Association(JOA)score,Oswestry Disability Index(ODI),degree of pain in the lower back and lower limbs,and postoperative complications were compared between the groups.Results The Cobb angle of the coronal lumbar scoliosis in the short-and long-segment fusion groups was significantly higher than that before surgery(P<0.05).At the 6th month after surgery,the intervertebral foramen height,intervertebral space height,intervertebral foramen area,spinal canal area,and spinal canal diameter in both groups increased,and those in the short-segment fusion group were higher than those in the long-segment fusion group(P<0.05);at the 6th month after the operation,the JOA scores of the short-segment and long-segment fusion groups were higher than those before surgery,and the JOA score of the short-segment fusion group was higher than that of the long-segment fusion group(P<0.05).The ODI score was lower than that before surgery in the short-and long-segment fusion groups,and the ODI score in the short-segment fusion group was lower than that in the long-segment fusion group(P<0.05).At the 6th month after surgery,the pain scores of the lower back and lower limbs in the short-and long-segment fusion groups were significantly higher than those before surgery(P<0.05).There were two cases of dural tears during decompression caused by lamina dura adhesion in the long-segment fusion group,and no serious complications were observed in the short-segment fusion group.Conclusions Both short-and long-segment decompression fixation fusion using a posterior approach can achieve good therapeutic effects for treating degenerative lumbar scoliosis.However,compared to the long-segment fusion group,the short-segment fusion group undergoing short-segment decompression fixation fusion through a posterior approach had a shorter surgical period,lower intraoperative blood loss,better recovery of lumbar function,and a lower risk of postoperative complications.

Objective Developing a new type of full-face respiratory protective mask for nuclear facility sites to enhance the sound transmission function and improve the facial adaptability. Methods Combined with feedback from on-site practical needs, this study utilized finite element simulation and ergonomic design methods to investigate the voice transmission units of full-face masks and the facial features of workers at key nuclear facilities. Based on the research results, a new full-face respiratory protection mask structure was designed. Results The optimized structure of passive thin film voice transmission unit significantly enhanced voice transmission efficiency, reducing average voice transmission loss by approximately 70% compared to the control group using thin plate units of equivalent thickness. The existing facial feature test panels insufficiently cover and unevenly classify the facial features of workers at key nuclear facilities. In this study, a specialized test panel based on measurement data achieved a total coverage of 98.5% with high distribution uniformity within each class, providing effective guidance for redesigning full-face mask structural parameters. In comparison to foreign products currently utilized in nuclear facilities, the newly designed full-face mask structure exhibited excellent tightness and structural safety and reliability, and can be cleaned, decontaminated, and reused. Conclusion The results of this study provide significant guidance for improving and optimizing full-face respiratory protection mask used at nuclear facilities, as well as promoting domestic production of high-quality full-face respiratory protection masks.

Objective:Three occupational health risk assessment methods were used to assess the occupational health risk of noise exposed posts in an automobile manufacturing enterprise. According to the results, the selection of risk assessment methods and risk management of such occupational noise enterprises were provided.Methods:Form April to November 2021, The occupational health field survey was carried out in an automobile manufacturing industry in Tianjin. The occupational health MES risk assessment method, occupational health risk index risk assessment method and Australian occupational hazard risk assessment method were used to evaluate the occupational health risk of noise-exposed posts in this enterprise, and the evaluation results of different methods were analyzed and compared.Results:The average value of LAeq, 8 h in the four workshops of automobile manufacturing industry was 82.95 dB (A) , and the noise detection exceeding rate was 22.41% (26/116) . The LAeq, 8h and exceeding rate noise of welding workshop were higher than those of other workshops (χ 2=23.56, 32.94, P<0.01) . The three occupational health risk assessment methods have the same risk assessment results for the four major workshops. The assembly and painting workshops are level 4 risk (possible risk) , and the stamping and welding workshops are level 3 risk (significant risk) . Conclusion:Occupational noise has certain potential hazards to workers in automobile manufacturing enterprises. Therefore, in the future work, corresponding organizational management measures should be taken to improve the working environment and reduce the actual exposure level of workers in order to protect the health of occupational workers.