Vascular dementia （VaD） is a cognitive dysfunction syndrome caused by cerebrovascular disease and is the second most common type of dementia worldwide， following Alzheimer's disease. The pathological mechanisms of VaD are complex， involving multiple biological processes， including angiogenesis， neuroinflammation， apoptosis， and oxidative stress. Among these， angiogenesis is a key process in VaD pathology and is primarily regulated through the vascular endothelial growth factor （VEGF） signaling pathway. In recent years， traditional Chinese medicine （TCM） has gradually gained attention in the treatment of VaD， particularly the therapeutic approach of benefiting Qi， activating blood circulation， and resolving blood stasis， which has demonstrated unique advantages in clinical practice. This method， based on the TCM theory of Qi and blood， emphasizes improving the pathological state of ''blood stasis'' by harmonizing the circulation of Qi and blood， and its scientific basis has been increasingly elucidated by modern pharmacological studies. This article systematically integrates the TCM concept of ''removing stasis to promote regeneration'' with the modern medical mechanism of neoangiogenesis and reviews the current research on promoting neoangiogenesis through the benefiting Qi， activating blood circulation， and resolving blood stasis in VaD treatment. It covers research progress on single Chinese medicine and compound formulas that promote neoangiogenesis， reduce apoptosis， and improve cerebral hemodynamics through multi-target and multi-pathway synergistic effects. Furthermore， this article explores the therapeutic approach of combining acupuncture and moxibustion with Chinese medicine formulas， breaking through the traditional single-treatment model. The synergistic treatment of acupuncture and herbal medicine not only enhances neoangiogenesis but also improves cognitive function and quality of life in VaD patients via multiple pathways. By comparing the advantages and limitations of modern medicine and TCM in VaD treatment， this article notes that while modern medicine excels in elucidating pathological mechanisms and targeted therapies， it is limited in overall regulation and multi-target interventions. TCM， through the comprehensive effects of multiple components and targets， is better suited to address the complex pathological features of VaD. However， current research on TCM for VaD still has limitations， including incompletely clarified mechanisms and insufficient clinical studies. Therefore， future research should further integrate multidisciplinary approaches， such as modern pharmacology and molecular biology， to deeply explore TCM resources and investigate diverse interdisciplinary collaborative treatment models， providing new ideas and strategies for VaD therapy.

Objective To analyze the relationship between small dense low-density lipoprotein(sd-LDL)and lipoprotein(a)and carotid plaque stability in patients with acute cerebral infarction(ACI).Methods A total of 160 elderly ACI patients admitted in our hospital from February 2020 to February 2024 were retrospectively recruited.All of them received cervical color Doppler ultra-sound examination,and according to carotid plaque status,they were divided into non-plaque group(43 cases),stable plaque group(56 cases)and unstable plaque group(61 cases).Another 40 healthy individuals taking physical examination in our hospital during the same period served as control group.The clinical data and sd-LDL and Lp(a)levels were compared among the 4 groups to evaluate the predictive value of sd-LDL and Lp(a)levels for unstable plaques.Results When compared with the non-plaque group,the NIHSS score and LDL-C level were significantly in-creased in the stable and unstable plaque groups,and the TC level was obviously elevated while that of HDL-C was notably reduced in the unstable plaque group,and the NIHSS score and TC,TG and LDL-C levels were remarkably declined while that of HDL-C elevated in the control group(P＜0.05).The NIHSS score and LDL-C,sdLDL and Lp(a)levels were elevated while that of HDL-C was lowered in the unstable plaque group than the stable plaque group(P＜0.05),and the Lp(a)level in the control group was obviously decreased than that of the stable plaque group(P＜0.05).Pearson correlation analysis showed that sd-LDL and Lp(a)levels were positively cor-related with NIHSS score and TC,TG and LDL-C(P＜0.05,P＜0.01),and negatively with HDL-C(P＜0.01).Binary logistic regression analysis revealed that NIHSS score and LDL-C,sd-LDL and Lp(a)levels were risk factors,and HDL-C was a protective factor for unstable carotid plaque in ACI patients(P＜0.01).ROC curve analysis indicated that the AUC value of sd-LDL,Lp(a)and their combination in predicting carotid plaque stability was 0.830,0.847 and 0.921,respectively,and the sensitivity of combined detection was higher than that of sd-LDL or Lp(a)alone(93.44％vs 88.52％and 86.89％,P=0.000).Conclusion Plasma sd-LDL and Lp(a)levels have a certain association with carotid plaque stability in ACI patients,and they can be used as relevant reference indicators in clinical practice.

Objective To analyze the relationship between small dense low-density lipoprotein(sd-LDL)and lipoprotein(a)and carotid plaque stability in patients with acute cerebral infarction(ACI).Methods A total of 160 elderly ACI patients admitted in our hospital from February 2020 to February 2024 were retrospectively recruited.All of them received cervical color Doppler ultra-sound examination,and according to carotid plaque status,they were divided into non-plaque group(43 cases),stable plaque group(56 cases)and unstable plaque group(61 cases).Another 40 healthy individuals taking physical examination in our hospital during the same period served as control group.The clinical data and sd-LDL and Lp(a)levels were compared among the 4 groups to evaluate the predictive value of sd-LDL and Lp(a)levels for unstable plaques.Results When compared with the non-plaque group,the NIHSS score and LDL-C level were significantly in-creased in the stable and unstable plaque groups,and the TC level was obviously elevated while that of HDL-C was notably reduced in the unstable plaque group,and the NIHSS score and TC,TG and LDL-C levels were remarkably declined while that of HDL-C elevated in the control group(P＜0.05).The NIHSS score and LDL-C,sdLDL and Lp(a)levels were elevated while that of HDL-C was lowered in the unstable plaque group than the stable plaque group(P＜0.05),and the Lp(a)level in the control group was obviously decreased than that of the stable plaque group(P＜0.05).Pearson correlation analysis showed that sd-LDL and Lp(a)levels were positively cor-related with NIHSS score and TC,TG and LDL-C(P＜0.05,P＜0.01),and negatively with HDL-C(P＜0.01).Binary logistic regression analysis revealed that NIHSS score and LDL-C,sd-LDL and Lp(a)levels were risk factors,and HDL-C was a protective factor for unstable carotid plaque in ACI patients(P＜0.01).ROC curve analysis indicated that the AUC value of sd-LDL,Lp(a)and their combination in predicting carotid plaque stability was 0.830,0.847 and 0.921,respectively,and the sensitivity of combined detection was higher than that of sd-LDL or Lp(a)alone(93.44％vs 88.52％and 86.89％,P=0.000).Conclusion Plasma sd-LDL and Lp(a)levels have a certain association with carotid plaque stability in ACI patients,and they can be used as relevant reference indicators in clinical practice.

Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.
Mice ; Animals ; Adipose Tissue, Brown ; Sirtuin 1/pharmacology* ; Diabetes Mellitus, Type 2/metabolism* ; AMP-Activated Protein Kinases/metabolism* ; Morus/metabolism* ; Flavonoids/metabolism* ; Prospective Studies ; Signal Transduction ; Adipose Tissue, White ; Plant Leaves ; Uncoupling Protein 1/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism*

ObjectiveTo investigate the effect of rutin on the browning of 3T3-L1 preadipocytes and the mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the effect of different concentration of rutin （3.125， 6.25， 12.5， 25， 50， 100， 200 μmol·L^-1） on 3T3-L1 cell activity， and Western blot to examine the effect of rutin （12.5， 25， 50 μmol·L^-1） on the expression of thermogenesis-associated proteins uncoupling protein 1 （UCP1）， PR domain containing 16 （PRDM16） and peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） in adipocytes. After the optimal concentration of rutin was determined， the effect of rutin on lipid droplet formation in adipocytes was observed based on oil red O staining， and the expression of nuclear respiratory factor 1 （NRF1）， nuclear respiratory factor 2 （NRF2） and mitochondrial transcription factor A （TFAM）， which were the landmark proteins of mitochondrial biosynthesis， was detected by Western blot. ResultCompared with the blank group， 200 μmol·L^-1 rutin inhibited 3T3-L1 cell activity （P<0.01）. Compared with the blank group， at the concentration of 12.5， 25， 50 μmol·L^-1 rutin significantly promoted the expression of thermogenesis-associated proteins （UCP1， PRDM16， and PGC-1α） （P<0.01）， which was determined as the optimal concentration. Compared with the blank group， 50 μmol·L^-1 rutin significantly increased the immunofluorescence intensity of mitochondrial UCP1 protein in 3T3-L1 cells （P<0.01） and the expression of the markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM） （P<0.01）. In addition， 50 μmol·L^-1 rutin significantly inhibited lipid droplet formation of 3T3-L1 adipocytes （P<0.01）. ConclusionRutin inhibited lipid droplet deposition in 3T3-L1 adipocytes and increased the expression of thermogenesis-related proteins （UCP1， PRDM16， and PGC-1α） and markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM）， thereby inducing the browning of 3T3-L1 adipocytes. This lays a basis for the development of drugs that safely regulate the browning of white cells.

BACKGROUND: In light of the significant clinical benefits of antibody-drug conjugates in clinical trials, the human epidermal growth factor receptor 2 (HER2)-low category in breast cancers has gained increasing attention. Therefore, we studied the clinicopathological characteristics of Chinese patients with hormone receptor (HR)-positive/HER2-low early-stage breast cancer and developed a recurrence risk prediction model. METHODS: Female patients with HR-positive/HER2-low early-stage breast cancer treated in 29 hospitals of the Chinese Society of Breast Surgery (CSBrS) from Jan 2015 to Dec 2016 were enrolled. Their clinicopathological data and prognostic information were collected, and machine learning methods were used to analyze the prognostic factors. RESULTS: In total, 25,096 patients were diagnosed with breast cancer in 29 hospitals of CSBrS from Jan 2015 to Dec 2016, and clinicopathological data for 6486 patients with HER2-low early-stage breast cancer were collected. Among them, 5629 patients (86.79%) were HR-positive. The median follow-up time was 57 months (4, 76 months); the 5-year disease-free survival (DFS) rate was 92.7%, and the 5-year overall survival (OS) rate was 97.7%. In total, 412 cases (7.31%) of metastasis were observed, and 124 (2.20%) patients died. Multivariate Cox regression analysis revealed that T stage, N stage, lymphovascular thrombosis, Ki-67 index, and prognostic stage were associated with recurrence and metastasis ( P <0.05). A recurrence risk prediction model was established using the random forest method and exhibited a sensitivity of 81.1%, specificity of 71.7%, positive predictive value of 74.1%, and negative predictive value of 79.2%. CONCLUSION: Most of patients with HER2-low early-stage breast cancer were HR-positive, and patients had favorable outcome; tumor N stage, lymphovascular thrombosis, Ki-67 index, and tumor prognostic stage were prognostic factors. The HR-positive/HER2-low early-stage breast cancer recurrence prediction model established based on the random forest method has a good reference value for predicting 5-year recurrence events. REGISTRITATION ChiCTR.org.cn, ChiCTR2100046766.
Humans ; Female ; Breast Neoplasms/diagnosis* ; Ki-67 Antigen ; Receptor, ErbB-2 ; Prognosis ; Thrombosis ; Receptors, Progesterone

Traditional medications used for treating autoimmune diseases often come with a wide range of adverse effects. Current treatments focus mainly on symptom management, resulting in significant health issues and financial burdens for patients. Recently, clinical research has demonstrated the potential of helminths and their derivatives as effective therapies for autoimmune disorders. Helminths, being a near-natural immunomodulator, exhibit milder effects than broad-spectrum immunosuppressants and corticosteroids, thereby presenting a promising alternative for the treatment of autoimmune diseases. However, different helminths' therapeutic efficacy and mechanisms and their derivatives in treating autoimmune diseases may vary. Therefore, we aim to review recent clinical advancements in the use of helminths and their derivatives for treating inflammatory bowel disease, multiple sclerosis, and autism spectrum disorder, with a view to offering novel clinical treatment approaches.
Animals ; Humans ; Autism Spectrum Disorder ; Autoimmune Diseases/drug therapy* ; Helminths ; Inflammatory Bowel Diseases

Objective:To explore the effect of music therapy in patients with post-stroke cognitive impairment (PSCI) based on Meta-analysis.Methods:The randomized controlled trial (RCT) on the effect of music therapy in PSCI patients was searched through computer on China National Knowledge Infrastructure, WanFang, VIP, PubMed, Embase, Web of Science, and Cochrane Library. Researchers screened articles according to inclusion and exclusion criteria, evaluated quality, and extracted data. Meta-analysis of the data was conducted using RevMan 5.4 software. The search period was from the establishment of the database to April 6, 2022.Results:A total of 19 RCTs were included, including 1 496 study subjects. The results showed that music therapy could improve cognitive function [ SMD=1.31, 95% CI (1.00, 1.62), P<0.01], increase ability of daily living [ SMD=1.19, 95% CI (0.41, 1.96), P<0.05], relieve anxiety [ SMD=-1.38, 95% CI (-1.88, -0.88), P<0.01], and depression [ SMD=-2.40, 95% CI (-3.73, -1.07), P<0.01]in PSCI patients. Conclusions:Existing evidence suggests that music therapy has a certain improvement effect on the cognitive function of PSCI patients, and can enhance their ability of daily living, reduce negative emotions such as anxiety and depression.