Diabetic Peripheral Neuropathy （DPN） is one of the most common and harmful complications of type 2 diabetes. DPN's pathogenesis include high blood sugar-induced oxidative stress， inflammation， and mitochondrial dysfunction. These factors are combined to damage nerve fibers， leading to sensory issues， pain， and numbness. Through a coordinated effect， these factors trigger nerve fiber damage and lead to sensory abnormalities， pain and numbness in limbs， and other symptoms， seriously restricting patients' activities of daily living and mobility. Recent research highlights that cellular senescence plays a critical role in DPN. Cellular senescence is manifested by the loss of cell proliferation ability， and further aggravates nerve damage via oxidative stress， mitochondrial dysfunction， autophagy impairment， inflammatory reaction， and other mechanisms， accelerating DPN occurrence and progression. In terms of medical treatment， current methods focus on blood sugar control， pain relief medicine， and microcirculation improvement， while no therapy has been developed based on cellular senescence. In contrast， traditional Chinese medicine （TCM） shows a unique advantage in DPN prevention and treatment via cellular senescence modulation. TCM emphasizes a holistic approach， as well as syndrome differentiation and treatment， effective in anti-aging and nerve damage repair. Recent studies show that TCM active ingredients， including puerarin， ginsenosides， and berberine， can reduce inflammation， oxidative stress， and apoptosis via signaling pathway regulation， thereby slowing cellular senescence to alleviate nerve damage. Furthermore， TCM compounds such as Buyang Huanwutang， Taohong Siwutang， and Huangqi Guizhi Wuwutang exert synergistic effects on cellular senescence-related pathways to improve nerve health and reduce DPN clinical symptoms. Therefore， this paper reviews the literature related to the interaction between cellular senescence and DPN from the perspective of cellular senescence， summarizing the mechanism of DPN and TCM intervention strategies.

The deficiency of fingers due to various reasons leads to a certain degree of loss of full or part hand functions. Physical and mental health of patients are seriously affected, and patients have varying degrees of reduced quality of life. Prosthesis fingers play an important role in completing the body shape and enhancing patients’ self-confidence and self-esteem. However, how to make prosthesis fingers perform coordinated movements and restore complete functions is a crucial problem that urgently needs to be solved. This paper reviews the methods of brain-computer interface controlled fine finger movements and elaborates on the origin, current situation, and advancements of the development of this technology, laying a foundation for subsequent research, with the expectation of helping patients solve the problems arising from the insufficiency or absence of finger functions.

ObjectiveTo investigate the effects of Chaihu and Longgu Mulitang （CLMT） on hippocampal neural damage in the mouse model of depression via the extracellular signal-regulated protein kinase （ERK）/cAMP-response element-binding protein （CREB） signaling pathway. MethodsSeventy-eight male C57BL/6 mice were randomly allocated into normal control， model， low/medium/high-dose （2.89， 5.78， and 11.56 g·kg^-1， respectively） CLMT， and paroxetine （10 mg·kg^-1） groups. A depression model was established by chronic unpredictable mild stress （CUMS） combined with social isolation. Behavioral tests were carried out to evaluate depressive-like behaviors. Hematoxylin-eosin staining and Nissl staining were performed to assess hippocampal morphology and neuronal damage. Immunofluorescence was employed to detect glial fibrillary acidic protein （GFAP） and ionized calcium-binding adapter molecule 1 （Iba1）. Real-time PCR was employed to measure the mRNA levels of ERK and CREB. Western blot was employed to determine the expression of ERK/CREB pathway proteins and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. Molecular Operating Environment （MOE） software was used for molecular docking to evaluate the interactions between CLMT components and target proteins. ResultsCompared with the normal control group， the model group showed decreased sucrose preference （P0.01）， increased tail-suspension immobility time （P0.01）， decreased activity in the central region of the open field test （P0.01）， and decreased activity in the middle and open-arm region of the elevated plus maze test （P0.01）. The hippocampal area in the model group showed wrinkled cells and a reduction in the number of cells， neurons with reduced sizes and Nissl bodies， enhanced fluorescence intensity of GFAP and Iba1 （P0.01）， and down-regulated expression of phosphorylated （p）-ERK， p-CREB， and BDNF （P0.05， P0.01） and mRNA levels of ERK and CREB （P0.01）. Compared with the model group， the CLMT group showed increased body weight （P0.05， P0.01）， restored cell morphology， with only a small number of ruptured cells， normal neuronal structure and morphology with obvious nuclei and abundant Nissl bodies， weakened fluorescence intensity of GFAP and Iba1 （P0.05， P0.01）， up-regulated mRNA levels of ERK and CREB （P0.05， P0.01） and protein levels of phosphorylated （p）-ERK， p-CREB， and BDNF in the hippocampal tissue （P0.05， P0.01）. The results of molecular docking indicated that nine active ingredients in CLMT had good binding affinity with ERK and CREB. ConclusionCLMT may ameliorate the hippocampal nerve injury in the mouse model of depression by regulating the ERK/CREB pathway.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

Tubal ciliary movement is one of the essential transport mechanisms for female fertility, playing a key role in facilitating oocyte pickup and transporting the fertilized ovum. This movement is mediated by multiciliated cells and regulated by specific proteins and hormones that modulate ciliary number, length, polarity, beat frequency, and amplitude to ensure proper function. Genetic mutations, inflammatory stimuli, and hormonal fluctuations can impair ciliary activity or induce ciliary apoptosis, leading to ciliary dysfunction. Disorders of tubal ciliary movement are frequently observed in primary ciliary dyskinesia, pelvic inflammatory disease, polycystic ovary syndrome, and endometriosis, conditions commonly associated with female infertility. These disorders manifest as structural abnormalities of cilia, disrupted polarity, shortened ciliary length, reduced ciliary count, and decreased beat frequency and amplitude. Understanding the role of tubal ciliary movement in female infertility-related diseases, through immunohistochemistry and ultrastructural analysis, helps clarify underlying infertility mechanisms. Identifying abnormal inflammatory factors, hormonal environments, and gene expression, combined with advanced techniques for measuring ciliary protein and beat frequency, may offer novel clinical targets for early prevention and treatment of female infertility.
Humans ; Female ; Infertility, Female/etiology* ; Cilia/physiology* ; Polycystic Ovary Syndrome/physiopathology* ; Fallopian Tubes/physiopathology* ; Endometriosis/complications* ; Pelvic Inflammatory Disease/complications*

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

Objective To explore the chemical basis of Shenxianshengmai oral liquid.Method UHPLC-Q Exactive Focus MS/MS technology was used to identify the chemical components of Shenxianshengmai oral liquid.The chromatographic separation was performed on a Thermo Accucore aQ C18 column(150 mm×2.1 mm,2.6 μm)with mobile phase gradient elution of 0.1%formic acid aqueous solution(A)and methanol(B)for 0-13 min,5%-60%B;13-27 min,60%-95%B;27-30 min,95%B,the flow rate was 0.3 mL·min-1,and the column temperature was at 30℃.The mass spectrometry was performed by heating electrospray ionization(H-ESI)with positive and negative ion scanning modes.The scanning range was m/z 120-1800,and the collision energies were 30 eV,50 eV and 70 eV.Result A total of 160 components were identified,including 29 flavonoids,24 organic acids,21 alkaloids,19 terpenoids,15 phenylpropanoids,12 saponins and 40 other components.Six chemical constituents(rutin,psoralenoside,isopsoralenoside,psoralen,isopsoralen and bakuchiol)were confirmed by comparison with reference substances.Conclusion In this study,an UHPLC-Q Exactive Focus MS/MS method has been established for accurate,rapid and systematic identification of the constituents in Shenxian Shengmai oral liquid,which provides an important basis for clarifying the chemical basis and quality control.

Objective:To compare the prevalence and progression of subclinical atherosclerosis (SA) in populations with different cardiovascular disease (CVD) risks in China, and clarify the relationship between CVD risk stratification and SA.Methods:All participants were from Beijing Community-Based Cohort of Atherosclerosis. A total of 1 462 participants underwent carotid ultrasound and coronary computed tomography scan during 2008-2009 and 2013-2014. After excluding 191 participants with history of CVD and incomplete baseline data, 1 271 participants were included in final analysis. The 10-year CVD risk for participants were calculated based on the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) equation, and risk stratification was performed. The prevalence and progression of SA was determined by carotid intima-media thickness (cIMT), carotid plaque score and coronary artery calcification (CAC) score.Results:In the participants included in this study, 536 (42.2%), 418 (32.9%) and 317 (24.9%) were classified to have low, intermediate and high 10-year risk, respectively. With the rising level of 10-year risk, the proportion of patients with SA and SA progression increased. In low, intermediate and high CVD risk groups, the proportions of participants with CAC were 16.4%, 36.4% and 52.0% (trend P<0.001); and 15.4%, 36.4% and 53.6% had progression of CAC during follow-up, respectively (trend P<0.001); compared with low-risk group, RRs for CAC progression of intermediate and high-risk groups were 2.316 (95% CI: 1.714-3.129) and 3.322 (95% CI: 2.472-4.463), respectively (trend P<0.001). The trend of relationship between CVD risk stratification and cIMT and carotid plaque progression were consistent with CAC. Conclusions:This current study shows CVD risk stratification is closely related to the prevalence and progression of atherosclerosis in Chinese population. However, many people with low CVD risk have atherosclerotic change in their carotid and coronary artery.

BACKGROUND:The reciprocal force generated by the molar distalization with clear aligners can lead to anchorage loss.The effect of arch shapes and missing second premolars on anchorage has not been reported. OBJECTIVE:To analyze the effect of arch shapes and missing second premolars on anchorage during molar distalization with clear aligners using the finite element method. METHODS:Cone-beam CT data from an adult male were acquired from the database to establish the maxilla-upper dentition-periodontium-rectangular attachment-clear aligner model.The distal movement amount designed on the bilateral second molars was set to 0.25 mm.First,there were two groups in the study:second premolar bilateral presence and absence groups.Then,four subgroups in each group were created:tapered arch,ovoid arch,square Class Ⅱ Division 1 arch,and Class Ⅱ Division 2 arch groups.The Ansys software was used to calculate the displacement of the anchorage tooth and the stress of the periodontal ligament. RESULTS AND CONCLUSION:Mesial tipping and extrusion of first molars and premolars,labial inclination and intrusion of anterior teeth occurred during the upper second molar distalization with clear aligners.When the bilateral second premolars were missing,the mesial displacement of first molars increased significantly while that of first premolars and anterior teeth decreased in all groups.The square Class Ⅱ Division 1 arch group showed the least anterior labial inclination,while the tapered arch group showed the most.There was no significant difference between the ovoid arch group and the tapered arch group.Moreover,the magnitude of tipping in the square Class Ⅱ Division 2 arch group was slightly higher than that in the Class Ⅱ Division 1 arch group.The stress of the periodontal ligament of the anchorage teeth was concentrated on the cervical and apical regions of the teeth.And the lowest stress level was detected in the square arch group.Compared with the other groups,the stress on the labial cervical area of the periodontal ligaments was also significantly relieved in the square arch group.To conclude,the square arch is more favorable in terms of anterior anchorage control and periodontal ligament stress distribution.Anterior labial inclination efficiency can be increased in cases of Class Ⅱ Division 2 by designing the anterior labial inclination in conjunction with molar distalization.If the second premolar is missing during molar distalization,it is not conducive to opening up the space in the area of the missing tooth.

BACKGROUND:The thin alveolar bone in the lower anterior region increases the risk of labial bone resorption when intruding the teeth with clear aligners.The effect of sagittal overcorrection design on the labiolingual control of mandibular anterior teeth intrusion has not been fully investigated. OBJECTIVE:To explore the effect of overcorrection on the changes in the displacement and stress of the mandibular anterior teeth,especially the cervical and apical regions. METHODS:Through a male volunteer cone-beam CT data,the three-dimensional reconstruction of the mandible and teeth was conducted in the MIMICS and GEOMAGIC software.Moreover,the models of periodontal ligaments,attachments,and appliances were created in the SOLIDWORKS software.First,the study was divided into canine intrusion group and incisor intrusion group.Then,the overcorrection(0°,1°,2°)was designed on the bilateral mandibular central and lateral incisors.A total of six models were established.The models were assembled and imported into the ANSYS software to analyze and calculate the displacement and stress level. RESULTS AND CONCLUSION:(1)In the canine intrusion group,canines intruded and tipped lingually while incisors extruded and tipped lingually.In the incisor intrusion group,canines extruded and tipped lingually while incisors intruded and tipped lingually.(2)Without overcorrection,the incisors necks moved lingually while apexes moved labially.With overcorrection,the incisors tended to be upright,followed by labial tilt.The least cervical and apical displacements were detected under 1° overcorrection.(3)With overcorrection,the incisal cervical stress concentration area shifted from labial to lingual in the canine intrusion group,whereas the stress concentration area shifted from lingual to labial in the incisor intrusion group.(4)The incisors tended to tilt lingually when intruding the mandibular anterior teeth with clear aligners.The sagittal overcorrection design was conductive to maintain the stable position of incisors.However,the amount of overcorrection should be moderate.Excessive overcorrection might increase the labial inclination tendencies of incisors.