Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

Alzheimer's disease (AD), characterized by β-amyloid (Aβ) aggregation and neuroinflammation, remains a formidable clinical challenge. Herein, we present an innovative nose-to-brain delivery platform utilizing lactoferrin (Lf)-functionalized lipid nanoparticles (LNPs) co-encapsulating α-mangostin (α-M) and β-site APP cleaving enzyme 1 (BACE1) siRNA (siB). This dual-modal therapeutic system synergistically combines the neuroprotective and microglia-reprogramming capabilities of α-M with the transcriptional silencing of BACE1 via siB, thereby simultaneously inhibiting Aβ production and enhancing its clearance. Fabricated via a microfluidic approach, the LNPs exhibited uniform particle size distribution, great encapsulation efficiency, and robust colloidal stability. Upon intranasal administration, Lf-functionalization enabled superior brain-targeting efficacy through receptor-mediated transcytosis. In vitro studies demonstrated that α-M reversed Aβ-induced low-density lipoprotein receptor downregulation, promoting microglial phagocytosis and autophagic degradation of Aβ, while siB effectively suppressed BACE1 expression, abrogating Aβ synthesis. In vivo investigations in APP/PS1 transgenic mice revealed remarkable cognitive recovery, substantial Aβ plaque reduction, and alleviation of neuroinflammation and oxidative stress. This intricately designed LNP system, exploiting a non-invasive and efficient nose-to-brain delivery route, provides a biocompatible, synergistic, and transformative therapeutic strategy for the multifaceted management of AD.

BACKGROUND:Cervical rotation-traction manipulation is effective and safe in the treatment of cervical spondylotic radiculopathy,and has been widely used in clinical work.However,its effects on the biomechanics of cervical vertebra and intervertebral disc and the area of intervertebral foramen have not been systematically clarified. OBJECTIVE:Based on the finite element analysis technique,a relevant research and analysis were carried out to provide digital evidence for the mechanism of effect of cervical rotation-traction manipulation in the treatment of cervical spondylotic radiculopathy. METHODS:The CT image data of a volunteer with no neck diseases were selected as the finite element model material at its left-handed physiological limit position.The initial construction of the finite element model was completed by Mimics 19.0 software,Geomagic Studio 2013 software,Hypermash 14.0 software,and ANSYS Workbench 2020 R2 software,respectively.Based on the literature,the grid division of cervical structure and the assignment of elastic modulus and elastic coefficient were completed.Based on the previous work of the team,the mechanical effects of cervical rotation-traction manipulation were simulated on the model.Effects of cervical rotation-traction manipulation on the mechanical parameters of each vertebral body and intervertebral disc in C3-T1 segment and on the cervical lateral foramen area were analyzed. RESULTS AND CONCLUSION:(1)During cervical rotation-traction manipulation,the stress of bone structure was significantly higher than that of soft tissue such as intervertebral disc.(2)When operating the technique,the stress at the top of each cervical vertebra was higher,the stress at the bottom was lower,and the stress at the facet joint and transverse process was lower.The stress at the top of the intervertebral disc was lower,the stress at the bottom was higher,but the highest point of the intervertebral disc stress was outside the top.(3)In addition,after loading the lifting force,the projected area of the C6/C7 intervertebral foramen increased significantly compared with that before loading.(4)It is indicated that the cervical rotation-traction manipulation has the mechanical characteristics of changing the stress structure of the cervical spine itself,and can expand the C6/7 intervertebral cervical foramen area on the opposite side of the patient's cervical rotation,so as to achieve the purpose of treating cervical spondylotic radiculopathy.

Objective:To explore the effect of non-invasive intervention on preventing maternal breast tenderness, and to provide references for clinicians to select the optimal non-invasive intervention for the prevention of maternal breast tenderness.Methods:Literature focused on the effect of different non-invasive interventions to prevent maternal breast tenderness by randomized controlled trials design was searched in the databases, including China National Knowledge Infrastructure, VIP, Wanfang, SinoMed, PubMed, Web of Science, Embase and Cochrane Library, from inception to April 8, 2024. Two researchers independently screened the literature, extracted the data and evaluated the quality of the literature. Stata 16.0 was used to conduct a network Meta-analysis.Results:A total of 21 studies involving 2 298 women, covering 5 non-invasive interventions (low-frequency pulse electrotherapy, breast massage combined with low-frequency pulse electrotherapy, breast massage and acupoint massage, breast massage and acupoint massage combined with ear point pressure bean, breast massage and acupoint massage combined with external application of Chinese medicine). The network meta-analysis results showed that, compared with routine care, five non-invasive interventions had statistically significant differences in reducing the incidence of maternal breast tenderness ( OR values ranging from 0.20 to 0.39, all P<0.05). Breast massage combined with low-frequency pulse electrotherapy ranked first in terms of effectiveness on preventing of breast tenderness. Conclusions:All five non-invasive interventions are effective on preventing maternal breast tenderness, with breast massage combined with low-frequency pulse electrotherapy being the most effective.

OBJECTIVE To explore the ameliorative effect of Tiaozhi Xiaoban Mixture on atherosclerosis and the potential role of long non-coding RNA(Linc RNA)in anti-atherosclerosis.METHODS A model of atherosclerosis was established in SD rats subjec-ted to a high-fat diet.At 4 weeks post-modeling,thoracic aortic tissues from atherosclerotic rats were collected for hematoxylin-eosin(HE)staining to systematically evaluate the anti-atherosclerotic effects of Tiaozhi Xiaoban Mixture at different doses.Biochemical kits were utilized to assess relevant indices related to blood lipid levels as well as liver and kidney function,thereby evaluating the impact of Tiaozhi Xiaoban Mixture on these parameters.Enzyme-linked immunosorbent assay(ELISA)was employed to measure serum inflam-mation markers influenced by Tiaozhi Xiaoban Mixture.Additionally,TUNEL staining and Western blot analysis were conducted to ex-amine the apoptotic effects of Tiaozhi Xiaoban Mixture on thoracic aorta tissue.Finally,qPCR was used to detect the expression levels of Line-HC,MALAT1,etc.,in order to evaluate how Tiaozhi Xiaoban Mixture affecting these specific RNA molecules.RESULTS Following treatment with Tiaozhi Xiaoban Mixture,the blood lipid profiles indicated that total cholesterol(TC),triglycerides(TG),and low-density lipoprotein cholesterol(LDL-C)were significantly down-regulated(P＜0.05,P＜0.01),while high-density lipopro-tein cholesterol(HDL-C)levels were up-regulated in the atherosclerotic rats.Moreover,serum levels of liver and kidney function markers such as aspartate aminotransferase(AST),alanine aminotransferase(ALT),blood urea nitrogen(BUN),and creatinine(Cr)exhibited down-regulation(P＜0.05,P＜0.01).Additionally,pro-inflammatory factors including interleukin-6(IL-6),interleukin-1 beta(IL-1β),tumor necrosis factor-alpha(TNF-α),high-sensitivity C-reactive protein(hs-CRP),and matrix metallopeptidase 9(MMP-9)were also reduced(P＜0.01),whereas the anti-inflammatory factor interleukin-10(IL-10)was found to be elevated(P＜0.01).Furthermore,after oral administration of Tiaozhi Xiaoban Mixture,expression levels of apoptosis-related factors NLRP3,ASC,Cleaved Caspase-1,Cleaved IL-1 β,Puma,Bax,Noxa,and MDM2 in thoracic aorta tissues from the atherosclerotic rats showed sig-nificant down-regulation(P＜0.05,P＜0.01).Notably,following treatment with Tiaozhi Xiaoban Mixture,mRNA levels of Linc-HC decreased while mRNA expression of MALAT1 increased(P＜0.05,P＜0.01).CONCLUSION Tiaozhi Xiaoban Mixture may inhibit the expression of Linc-HC and up-regulate the expression of MALAT1 to reduce the formation of atherosclerotic plaque,improve ab-normal blood lipids and liver and kidney function,alleviate inflammation and inhibit apoptosis.

OBJECTIVE To explore the ameliorative effect of Tiaozhi Xiaoban Mixture on atherosclerosis and the potential role of long non-coding RNA(Linc RNA)in anti-atherosclerosis.METHODS A model of atherosclerosis was established in SD rats subjec-ted to a high-fat diet.At 4 weeks post-modeling,thoracic aortic tissues from atherosclerotic rats were collected for hematoxylin-eosin(HE)staining to systematically evaluate the anti-atherosclerotic effects of Tiaozhi Xiaoban Mixture at different doses.Biochemical kits were utilized to assess relevant indices related to blood lipid levels as well as liver and kidney function,thereby evaluating the impact of Tiaozhi Xiaoban Mixture on these parameters.Enzyme-linked immunosorbent assay(ELISA)was employed to measure serum inflam-mation markers influenced by Tiaozhi Xiaoban Mixture.Additionally,TUNEL staining and Western blot analysis were conducted to ex-amine the apoptotic effects of Tiaozhi Xiaoban Mixture on thoracic aorta tissue.Finally,qPCR was used to detect the expression levels of Line-HC,MALAT1,etc.,in order to evaluate how Tiaozhi Xiaoban Mixture affecting these specific RNA molecules.RESULTS Following treatment with Tiaozhi Xiaoban Mixture,the blood lipid profiles indicated that total cholesterol(TC),triglycerides(TG),and low-density lipoprotein cholesterol(LDL-C)were significantly down-regulated(P＜0.05,P＜0.01),while high-density lipopro-tein cholesterol(HDL-C)levels were up-regulated in the atherosclerotic rats.Moreover,serum levels of liver and kidney function markers such as aspartate aminotransferase(AST),alanine aminotransferase(ALT),blood urea nitrogen(BUN),and creatinine(Cr)exhibited down-regulation(P＜0.05,P＜0.01).Additionally,pro-inflammatory factors including interleukin-6(IL-6),interleukin-1 beta(IL-1β),tumor necrosis factor-alpha(TNF-α),high-sensitivity C-reactive protein(hs-CRP),and matrix metallopeptidase 9(MMP-9)were also reduced(P＜0.01),whereas the anti-inflammatory factor interleukin-10(IL-10)was found to be elevated(P＜0.01).Furthermore,after oral administration of Tiaozhi Xiaoban Mixture,expression levels of apoptosis-related factors NLRP3,ASC,Cleaved Caspase-1,Cleaved IL-1 β,Puma,Bax,Noxa,and MDM2 in thoracic aorta tissues from the atherosclerotic rats showed sig-nificant down-regulation(P＜0.05,P＜0.01).Notably,following treatment with Tiaozhi Xiaoban Mixture,mRNA levels of Linc-HC decreased while mRNA expression of MALAT1 increased(P＜0.05,P＜0.01).CONCLUSION Tiaozhi Xiaoban Mixture may inhibit the expression of Linc-HC and up-regulate the expression of MALAT1 to reduce the formation of atherosclerotic plaque,improve ab-normal blood lipids and liver and kidney function,alleviate inflammation and inhibit apoptosis.

Objective:To explore the effect of non-invasive intervention on preventing maternal breast tenderness, and to provide references for clinicians to select the optimal non-invasive intervention for the prevention of maternal breast tenderness.Methods:Literature focused on the effect of different non-invasive interventions to prevent maternal breast tenderness by randomized controlled trials design was searched in the databases, including China National Knowledge Infrastructure, VIP, Wanfang, SinoMed, PubMed, Web of Science, Embase and Cochrane Library, from inception to April 8, 2024. Two researchers independently screened the literature, extracted the data and evaluated the quality of the literature. Stata 16.0 was used to conduct a network Meta-analysis.Results:A total of 21 studies involving 2 298 women, covering 5 non-invasive interventions (low-frequency pulse electrotherapy, breast massage combined with low-frequency pulse electrotherapy, breast massage and acupoint massage, breast massage and acupoint massage combined with ear point pressure bean, breast massage and acupoint massage combined with external application of Chinese medicine). The network meta-analysis results showed that, compared with routine care, five non-invasive interventions had statistically significant differences in reducing the incidence of maternal breast tenderness ( OR values ranging from 0.20 to 0.39, all P<0.05). Breast massage combined with low-frequency pulse electrotherapy ranked first in terms of effectiveness on preventing of breast tenderness. Conclusions:All five non-invasive interventions are effective on preventing maternal breast tenderness, with breast massage combined with low-frequency pulse electrotherapy being the most effective.

Objective·To assess the levels of pregnancy-related stress,pre-pregnancy health care behaviors,and coping styles among pregnant women,analyze the influencing factors of pregnancy stress and provide insights for the management of pregnancy health in expectant mothers.Methods·A total of 265 pregnant women receiving treatment at the Obstetrics Clinic of the Affiliated Hospital of Zunyi Medical University from April to August 2022 were included as participants.General information questionnaires,pre-pregnancy health care behavior questionnaires,pregnancy stress scales and simple coping style questionnaires were utilized for data collection.After obtaining the consent of the patients,assessments on pregnancy stress levels,pre-pregnancy health care behaviors,and coping styles were conducted.Results·The overall average score for pregnancy stress among pregnant women was 1.05±0.41.Multiple linear regression analysis revealed that age,number of pregnancies,history of threatened abortion,fetal gender expectations,attending prenatal education classes or reviewing relevant manuals significantly influenced pregnancy-related stresses(P<0.05).The score of pre-pregnancy health care behavior was 10.09±2.63 with proportions indicating high-level,medium-level,and low-level adherence at 17.36%,54.34%,and 28.30%.In pregnant women,the total score for coping styles was 27.22±9.68,with a positive coping dimension score of 17.79±9.84 and a negative coping dimension score of 9.42±7.39.Pearson correlation analyses demonstrated a negative association between pregnancy-related stresses and pre-pregnancy health care behaviors(r=-0.313,P<0.01),and a negative correlation between pregnancy-related stresses and coping styles(r=-0.163,P<0.01),while a positive relationship existed between pre-pregnancy health care behaviors and coping styles(r=0.220,P<0.01).Conclusion·Pregnant women experience moderate levels of pressure during their pregnancies and have suboptimal engagement in preconceptional healthcare practices.Nursing staff should intensify efforts towards disseminating knowledge on preconceptional healthcare practices,thereby empowering women of childbearing age to actively acquire pertinent reproductive-health knowledge prior to conception so that minimizing adverse maternal-infant outcomes,optimizing maternal-infant healthcare strategies,and enhancing overall well-being can be achieved through these measures.

Objective:To compare the difference of prognosis in ⅢCr stage cervical cancer patients with different T stage and lymph node status who received radical radiotherapy.Methods:Clinical data of 279 patients with ⅢCr stage cervical cancer treated with radical radiotherapy at Zhejiang Cancer Hospital from September 2013 to December 2016 were retrospectively analyzed. According to the latest American Joint Committee on Cancer (AJCC) TNM stage, all patients were divided into T 2a, T 2b, T 3a and T 3b stage groups, and N 1 and N 2 stage groups based on lymph node status. They were also divided into <1.85 cm and ≥1.85 cm groups according to the maximum short diameter of lymph node. In addition, they were assigned into ≤3 and>3 groups according to the number of lymph node metastasis. The differences of progression-free survival (PFS) and overall survival (OS) between patients with different T stage and lymph node status were compared by Kaplan-Meier test and log-rank test. Multivariate survival analysis was performed by Cox regression analysis. Results:Among 279 patients with ⅢCr stage cervical cancer receiving radical radiotherapy, 6 (2.2%) patients were diagnosed with stage T 2a stage, 109 (39.1%) patients with T 2b stage, 13 (4.7%) patients with T 3a stage, and 151 (54.1%) patients with T 3b stage. And 246 (88.2%) patients were diagnosed with N 1 stage and 33 (11.8%) patients with N 2 stage. According to the maximum short diameter of lymph nodes, there were 229 (82.1%) patients in the<1.85 cm group and 50 (17.9%) in the ≥1.85 cm group. According to the number of lymph node metastasis, there were 269 (96.4%) patients in the ≤3 group and 10 (3.6%) in the>3 group. There was no significant difference in the 5-year PFS ( P=0.136) and OS rates ( P=0.050) among patients with different T stages, and patients with T 3a stage had the worst prognosis (5-year OS rate was 38.5%). The 5-year PFS (48.0% vs. 64.2%, P=0.016) and OS rates (52.0% vs. 73.8%, P=0.001) in the ≥1.85 cm group were significantly lower than those in the<1.85 cm group. There was no significant difference in the 5-year PFS (61.0% vs. 63.6%, P=0.796) and OS rates (67.5% vs. 69.7%, P=0.770) between patients with N 1 and N 2 stages. There was no significant difference in the 5-year PFS (61.0% vs. 70.0%, P=0.653) and OS rates (67.3% vs. 80.0%, P=0.447) between patients in the number of metastatic lymph nodes ≤3 and>3 groups. The prognosis of patients with T 2b stage and the maximum short diameter ≥1.85 cm was the worst (5-year OS rate was 31.3%), while patients with T 2b stage and the maximum short diameter <1.85 cm obtained the best prognosis (5-year OS rate was 76.3%). Multivariate analysis showed that the maximum short diameter and radiation dose of lymph nodes were the independent relevant factors for the OS of ⅢCr stage cervical cancer patients (both P<0.05). Conclusions:Among ⅢCr stage cervical cancer patients receiving radical radiotherapy, clinical efficacy and prognosis significantly differ according to different T stage and lymph node status. Current staging system should be optimized to provide effective diagnostic and therapeutic regimens.

Objective:To investigate the early effect of repairing acetabular cartilage delamination with absorbable anchor under hip arthroscopy compared with conventional non-intervention.Methods:Retrospective cohort study was adopted. There were 24 Femoroacetabular Impingment (FAI) patients with acetabular cartilage delamination (ACD) receiving hip arthroscopy surgery in Peking University Third Hospital from May 2021 to August 2021. There were 14 males and 10 females with an average age of 36.3±7.2 years (range 23-53 years). There were 12 patients receiving acetabular cartilage repair with absorbable anchor (absorbable anchor group), and 12 patients in non-intervention group. The X-ray film indicators, α angle, lateral center edge angle (LCEA) and MRI measurement (acetabular cartilage gap, CG) were compared between the two groups. The pre- and post-operative hip functions were assessed by modified Harris Hip Score (mHHS), 12-item international hip outcome tool (iHOT12), hip outcome score-activities of daily living subscale (HOS-ADL), and hip outcome score-sports subscale (HOS-SS), along with visual analogue scale (VAS). The complications (infection, lower extremity deep venous thrombosis) were followed up, as well as the revisional hip arthroscopy surgery and total hip replacement surgery.Results:A total of 24 patients were followed up for 12.0±1.2 months (range 10-14 months). There was no significant difference between the two groups for age, BMI, and symptom onset time ( P>0.05). There was no significant difference between the two groups for the pre-operative α angle, LCEA, CG, mHHS, iHOT12, HOS-ADL, HOS-SS, and VAS scores ( P>0.05). At the last follow-up, there was no significant difference between the two groups for the α angle, LCEA, CG, mHHS, iHOT12, HOS-ADL, HOS-SS, VAS and satisfaction ( P>0.05). In the absorbable anchor group, the α angle was 47.2°±2.6° vs. 63.4°±3.3°, CG was 3.0±0.7 mm vs. 3.3±0.6 mm; mHHS was 73.6±16.0 vs. 57.7±15.4; iHOT12 was 67.6±22.5 vs. 50.6±15.0 after and before the surgery, with significant improvement ( P<0.05). As for the non-intervention group, there was significant decrease of post-operative α angle of 47.4°±2.6° compared to the pre-operative angle of 58.4°±8.1° ( P<0.05). There was no significant difference in LCEA, CG, mHHS, iHOT12, HOS-ADL, HOS-SS, and VAS scores before and after the surgery in non-intervention group comparison ( P>0.05). No complications, revision hip arthroscopy surgery or total hip replacement surgery occurred during the follow up. Conclusion:Good effect was yielded for absorbable anchor repairing acetabular cartilage delamination under hip arthroscopy, without additional risk of complications or revision surgery.