Triggering receptor expressed on myeloid cells 2 (TREM2)-mediated microglial phagocytosis is an energy-intensive process that plays a crucial role in amyloid beta (Aβ) clearance in Alzheimer's disease (AD). Energy metabolic reprogramming (EMR) in microglia induced by TREM2 presents therapeutic targets for cognitive impairment in AD. Jiawei Xionggui Decoction (JWXG) has demonstrated effectiveness in enhancing energy supply, protecting microglia, and mitigating cognitive impairment in APP/PS1 mice. However, the mechanism by which JWXG enhances Aβ phagocytosis through TREM2-mediated EMR in microglia remains unclear. This study investigates how JWXG facilitates microglial phagocytosis and alleviates cognitive deficits in AD through TREM2-mediated EMR. Microglial phagocytosis was evaluated through immunofluorescence staining in vitro and in vivo. The EMR level of microglia was assessed using high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) kits. The TREM2/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway was analyzed using Western blotting in BV₂ cells. TREM2^-/- BV₂ cells were utilized for reverse validation experiments. The Aβ burden, neuropathological features, and cognitive ability in APP/PS1 mice were evaluated using ELISA kits, immunohistochemistry (IHC), and the Morris water maze (MWM) test. JWXG enhanced both the phagocytosis of EMR disorder-BV₂ cells (EMRD-BV₂) and increased EMR levels. Notably, these effects were significantly reversed in TREM2^-/- BV₂ cells. JWXG elevated TREM2 expression, adenosine triphosphate (ATP) levels, and microglial phagocytosis in APP/PS1 mice. Additionally, JWXG reduced Aβ-burden, neuropathological lesions, and cognitive deficits in APP/PS1 mice. In conclusion, JWXG promoted TREM2-induced EMR and enhanced microglial phagocytosis, thereby reducing Aβ deposition, improving neuropathological lesions, and alleviating cognitive deficits.
Drugs, Chinese Herbal/pharmacology* ; Microglia/drug effects* ; Phagocytosis ; Cognitive Dysfunction/drug therapy* ; Metabolic Reprogramming ; Animals ; Mice ; Cell Line ; Receptors, Immunologic/metabolism* ; Membrane Glycoproteins/metabolism* ; Signal Transduction ; Amyloid beta-Peptides/metabolism* ; Energy Metabolism

Objective:To investigate the application of the conjugate gradient (CG) algorithm to treatment plan optimization for intensity-modulated brachytherapy (IMBT).Methods:The general Monte Carlo software TOPAS was utilized to simulate the 192Ir source of IMBT, and the unit dose contribution matrix was calculated. An objective function was established using the weighted least squares method and was solved using the CG algorithm to achieve optimized IMBT treatment plans. The optimization was validated using five clinical cervical cancer cases under modulation width 60°. The dose distributions of IMBT treatment plans under 45°, 60°, 90°, 120°, and 180° modulation widths were compared using the Wilcoxon test to determine the optimal IMBT treatment plan for cervical cancer treatment. Results:The CG algorithm successfully optimized IMBT treatment plans under modulation width 60° for five cases within 22.2 s on average. On the premise of sufficient target dose coverage, the average D2 cm 3 values of the bladder and rectum in IMBT treatment plans were 3.66 and 1.97 Gy, respectively, representing reductions of 0.54 and 0.69 Gy compared to traditional brachytherapy plans. For the five modulation widths, the D90% values of all IMBT treatment plans reached 6 Gy, without statistically significant differences ( P > 0.05). The average D2 cm 3 values of the bladder in IMBT treatment plans were significantly lower than those in the traditional brachytherapy plans( P<0.05), with modulation width 60° associated with the greatest reduction of 0.61 Gy. In contrast, the average D2 cm 3 values of the rectum under 45°, 60°, and 90° modulation widths decreased by 0.63, 0.54, and 0.45 Gy, respectively, compared to traditional plans, with statistically significant differences( P<0.05). Conclusions:The CG method enables rapid achievement of optimized IMBT treatment plans that meet clinical requirements, and modulation width 60° contributes to valid dosimetric optimization. This study can serve as a guide for the clinical implementation of IMBT.

Objective:To investigate the effectiveness of gastric-soleal turndown flap and knotless anchor bridging fixation via a modified incision in the treatment of chronic Achilles tendon rupture of Myerson type Ⅲ.Methods:A retrospective case series study was conducted to analyze the clinical data of the 18 patients who had been treated at Department of Minimally Invasive Orthopedics, Zhengzhou Orthopaedic Hospital from February 2020 to July 2023 for chronic Achilles tendon rupture of Myerson type Ⅲ by means of gastric-soleal turndown flap and knotless anchor bridging fixation via a modified incision. There were 15 males and 3 females, with an age of (37.2±6.8) years. All patients suffered from unilateral injury, involving 13 left sides and 5 right sides. Their body mass index was (22.6±2.5) kg/m 2. The operation time, blood loss, incision length, wound healing and complications were documented. The ankle dorsiflexion and plantar flexion at the last follow-up were compared between the affected side and the healthy side. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Achilles tendon total rupture score (ATRS) before operation were compared with those at the last follow-up. Results:All the 18 patients were followed up for (18.0±5.5) months. Their operation time was (69.1±5.2) minutes, blood loss (71.6±9.2) mL, incision at the broken end of the Achilles tendon (12.4±2.6) cm and incision at the proximal end (2.5±0.4) cm. At the last follow-up, the ankle dorsiflexion was 12.7°±1.9° and the ankle plantar flexion 35.2°±2.0° at the affected side, showing no significant difference from those at the healthy side (13.0°±2.1° and 34.7°±1.8°) ( P>0.05). The AOFAS ankle-hindfoot score was (89.4±3.4) points and the ATRS (85.3±3.2) points for the affected side at the last follow-up, showing significant improvements compared with the preoperative values [(54.2±4.2) points and (51.1±4.6) points] ( P<0.05). All the incisions healed at one stage after operation, with no such complications as incision infection or re-rupture of the Achilles tendon. One patient experienced mild pain at the anchor insertion site, but the pain disappeared 6 months after operation without any treatment. One patient had the symptoms of sural nerve injury which responded to 3 months of oral neurotrophic medication. Conclusion:In the treatment of chronic Achilles tendon rupture of Myerson type Ⅲ, gastric-soleal turndown flap and knotless anchor bridging fixation via a modified incision can result in limited invasion, a low incidence of complications, and definite effectiveness.

Alzheimer's disease (AD) is the leading neurodegenerative disorder in the nervous system, and there is still a lack of effective therapeutic drugs. Protecting neurons and synapses is crucial in reversing AD progression. Mesenchymal stem cell-derived exosome (MSC-Exo) is rich in various stem cell components such as proteins, RNAs, and DNAs; due to its strong ability in promoting nerve repair and inhibiting neuroinflammation, MSC-Exo is expected to become a potential choice for AD treatment. This article elaborates on the biological characteristics of MSC-Exo and its application and progress in AD treatment, aiming to provide reference for translational medicine research and clinical application of MSC-Exo in AD.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective:To explore the operioperative and long-term outcomes of inflatable mediastinoscopic resection of esophageal carcinoma (IVMTE) and minimally invasive Mckeown resection of esophageal carcinoma (MIME) in early esophageal cancer.Methods:This is a retrospective cohort study. A retrospectively analysis was conducted on 176 patients with cT1N0M0 esophageal cancer who underwent IVMTE or MIME at the Department of Thoracic Surgery, Anhui Provincial Hospital Affiliated with Anhui Medical University from April 2017 to April 2019. There were 128 males and 48 females, aged (66.4±7.7) years (range: 45 to 87 years). General data, perioperative outcomes, pathological data of the tumors, and complications were recorded. Independent sample t-test, χ2 test, or Wilcoxon rank-sum test was used to compare the data between the two groups. Propensity score matching was performed with gender, age, tumor location, differentiation degree, pT stage, pN stage, American Society of Anesthesiologists (ASA) classification, smoking history, and alcohol history were considered as covariates. The IVMTE group and MIME group were matched in a 1∶2 ratio using nearest neighbor match method with a caliper value of 0.02. Kaplan-Meier method was used to plot survival curves, with Log-rank test for univariate survival analysis. The Cox proportional hazards model was applied to analyze prognostic factors for overall survival, and subgroup stratification analysis was performed for pT stage. Results:After matching, the MIME group consisted of 54 cases, and the IVMTE group consisted of 27 cases. There were no statistically significant differences between the two groups in terms of gender, age, smoking history, alcohol history, ASA classification, tumor location, and other factors. The IVMTE group had shorter surgery time ( M(IQR), 220 (45) minutes vs. 245 (56) minutes, Z=2.950, P=0.003) and less intraoperative blood loss (100 (50) ml vs. 125 (100) ml, Z=2.193, P=0.028) compared to the MIME group. There were no differences between the two groups in the number and quantity of lymph node stations dissected, and the IVMTE group was not at a disadvantage in terms of the number of lymph nodes dissected around the recurrent laryngeal nerve (all P>0.05). The 1-, 3-, and 5-year overall survival (OS) rates and recurrence-free survival (RFS) rates were not significantly different between the two groups (all P>0.05). Subgroup analysis showed no significant difference in OS and RFS rates between the pT1 and pT2 subgroups (all P>0.05). Multivariate Cox regression analysis suggested that ASA classification ( HR=2.516, 95% CI: 1.126 to 5.624, P=0.025), pN stage ( HR=2.485, 95% CI: 0.984 to 6.274, P=0.046), and whether adjuvant therapy was given postoperatively ( HR=2.915, 95% CI: 1.304 to 6.515, P=0.009) were independent risk factors affecting 5-year OS rate. For 5-year RFS, pT stage ( HR=0.403, 95% CI: 0.194 to 0.838, P=0.011), pN stage ( HR=5.219, 95% CI: 2.401 to 11.346, P<0.01), and whether adjuvant therapy was given postoperatively ( HR=5.644, 95% CI: 2.691 to 11.838, P<0.01) were independent risk factors, while the surgical approach was not an independent risk factor affecting patient prognosis. Conclusion:The short-term and long-term effect of IVMTE in the treatment of early esophageal cancer is good, and it can achieve effects comparable to MIME.

The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL⁺ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL⁺ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.

Objective:To analyze the predictive effects of the Big Five personality traits and emotions on self-management behaviors in patients with type 2 diabetes mellitus (T2DM).Methods:This study was a cross-sectional research. From 2016 to 2020, community interventions for self-management among patients with chronic diseases were conducted in Hangzhou, targeting patients with type 2 diabetes recruited from 69 community health service centers across the city. The data for this study were derived from the baseline information collected during the community intervention. The Chinese Big Five Personality Inventory (CBF-PI-15), the Type 2 Diabetes Self-Management Scale (2-DSCS), the Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS) were employed for questionnaire assessments. Biochemical indicators, including postprandial 2-hour blood glucose, glycated hemoglobin (HbA 1c), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were measured. Spearman correlation analysis was used to examine the relationship between personality traits, relevant biochemical indicators, and self-management behaviors. Hierarchical regression analysis was employed to assess the predictive effects of the Big Five personality traits and emotions on self-management behaviors after controlling for demographic characteristics and factors related to health status. Results:A total of 839 patients were included in this study, comprising 518 females (61.75%) and 321 males (38.25%), with an average age of (66.92±8.67) years and an average disease duration of (8.87±6.91) years. There were significant differences in self-management behavior scores among patients with varying disease durations, educational levels, treatment methods, and levels of anxiety and depression ( t/F=6.172, 3.340, 4.699, 16.007, 27.127, all P<0.05). Neuroticism showed a negative correlation with various dimensions of self-management behaviors ( r=-0.130--0.073), while conscientiousness and agreeableness were positively correlated with various dimensions of self-management behaviors ( r=0.072-0.215). Dietary control score was negatively correlated with HbA 1c and LDL-C ( r=-0.106, -0.077), and regular exercise score was negatively correlated with postprandial 2-hour blood glucose, HbA 1c, TG, TC, HDL-C, and LDL-C ( r=-0.115--0.071). The total score of the 2-DSCS was negatively correlated with HbA 1c, TG, and TC ( r=-0.104--0.071). Patients with a disease duration exceeding 15 years and those receiving insulin injections or a combination of oral medication and insulin injections had higher total 2-DSCS score ( β=0.085, 0.146, 0.118, all P<0.05). Conversely, patients with higher HbA 1c and SDS standard scores had lower total 2-DSCS score ( β=-0.151, -0.328, both P<0.05), while those with higher agreeableness scores had higher total 2-DSCS score ( β=0.143, P<0.05). Conclusion:The traits of neuroticism, conscientiousness, and agreeableness within the Big Five Personality Traits, as well as anxiety and depressive emotions, are correlated with self-management behaviors. Specifically, agreeableness has a positive predictive effect on self-management behaviors, whereas depressive emotions have a negative predictive effect.

Objective:To investigate the application of the conjugate gradient (CG) algorithm to treatment plan optimization for intensity-modulated brachytherapy (IMBT).Methods:The general Monte Carlo software TOPAS was utilized to simulate the 192Ir source of IMBT, and the unit dose contribution matrix was calculated. An objective function was established using the weighted least squares method and was solved using the CG algorithm to achieve optimized IMBT treatment plans. The optimization was validated using five clinical cervical cancer cases under modulation width 60°. The dose distributions of IMBT treatment plans under 45°, 60°, 90°, 120°, and 180° modulation widths were compared using the Wilcoxon test to determine the optimal IMBT treatment plan for cervical cancer treatment. Results:The CG algorithm successfully optimized IMBT treatment plans under modulation width 60° for five cases within 22.2 s on average. On the premise of sufficient target dose coverage, the average D2 cm 3 values of the bladder and rectum in IMBT treatment plans were 3.66 and 1.97 Gy, respectively, representing reductions of 0.54 and 0.69 Gy compared to traditional brachytherapy plans. For the five modulation widths, the D90% values of all IMBT treatment plans reached 6 Gy, without statistically significant differences ( P > 0.05). The average D2 cm 3 values of the bladder in IMBT treatment plans were significantly lower than those in the traditional brachytherapy plans( P<0.05), with modulation width 60° associated with the greatest reduction of 0.61 Gy. In contrast, the average D2 cm 3 values of the rectum under 45°, 60°, and 90° modulation widths decreased by 0.63, 0.54, and 0.45 Gy, respectively, compared to traditional plans, with statistically significant differences( P<0.05). Conclusions:The CG method enables rapid achievement of optimized IMBT treatment plans that meet clinical requirements, and modulation width 60° contributes to valid dosimetric optimization. This study can serve as a guide for the clinical implementation of IMBT.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.