Atherosclerosis (AS) is a prevalent clinical vascular condition and serves as a pivotal pathological foundation for cardiovascular diseases. Understanding the pathogenesis of AS has significant clinical and societal implications, aiding in the development of targeted drugs. Neutrophils, the most abundant leukocytes in circulation, assume a central role during inflammatory responses and closely interact with AS, which is a chronic inflammatory vascular disease. Neutrophil extracellular traps (NETs) are substantial reticular formations discharged by neutrophils that serve as an immune defense mechanism. These structures play a crucial role in inducing dysfunction of the vascular barrier following endothelial cell injury. Components released by NETs pose a threat to the integrity of vascular endothelium, which is essential as it acts as the primary barrier to maintain vascular wall integrity. Endothelial damage constitutes the initial stage in the onset of AS. Recent investigations have explored the intricate involvement of NETs in AS progression. The underlying structures of NETs and their active ingredients, including histone, myeloperoxidase (MPO), cathepsin G, neutrophil elastase (NE), matrix metalloproteinases (MMPs), antimicrobial peptide LL-37, alpha-defensin 1-3, and high mobility group protein B1 have diverse and complex effects on AS through various mechanisms. This review aims to comprehensively examine the interplay between NETs and AS while providing insights into their mechanistic underpinnings of NETs in this condition. By shedding light on this intricate relationship, this exploration paves the way for future investigations into NETs while guiding clinical translation efforts and charting new paths for therapeutic interventions.
Extracellular Traps/physiology* ; Humans ; Atherosclerosis/immunology* ; Neutrophils/physiology* ; Leukocyte Elastase/metabolism* ; Peroxidase/physiology* ; Matrix Metalloproteinases/physiology* ; Cathepsin G/metabolism* ; Cathelicidins ; HMGB1 Protein/physiology* ; Histones ; Animals ; Endothelium, Vascular

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

BACKGROUND: Acupuncture has shown potential therapeutic benefits for individuals with simple obesity. However, some researchers argue that some of the effectiveness of acupuncture may be due to the placebo response. OBJECTIVE: To understand the placebo response of acupuncture treatment in simple obesity, a systematic review and meta-analysis was designed based on the comparison between sham acupuncture before and after treatment. SEARCH STRATEGY: Eight databases (PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang Database, China Biology Medicine Database, and Chinese Scientific Journals Database) were searched from inception to August 1, 2023. The MeSH search terms comprised obesity and acupuncture. INCLUSION CRITERIA: Randomized controlled trials (RCTs) using sham or placebo acupuncture as a control in treating obesity were enrolled. DATA EXTRACTION AND ANALYSIS: Two researchers independently extracted data, and the results were cross-checked after completion. Each RCT's detailed sham/placebo acupuncture treatment protocol was assessed according to the SHam Acupuncture REporting guidelines. The revised Cochrane risk-of-bias tool for randomized trials and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system were used to determine the risk of bias and quality of evidence, respectively. Body mass index (BMI) was defined as the primary outcome. Anthropometric parameters and laboratory test parameters related to obesity were defined as secondary outcomes. We used standardized mean difference (SMD) with 95% confidence interval (CI) to calculate treatment effects of outcomes. RESULTS: Fifteen RCTs with a total of 1250 patients were included. The BMI significantly decreased after treatment in the sham acupuncture group compared to baseline (SMD 0.37, 95% CI 0.09-0.66; I² = 81%, random model; P < 0.01). Treatment duration (P = 0.02) and other interventions significantly impacted the placebo response rate (P = 0.00). CONCLUSION The placebo response of sham acupuncture was strong in the RCTs for simple obesity, and the effect sizes differed between various outcomes. The treatment duration and other interventions emerged as potential influencing factors for the placebo response of sham acupuncture. Please cite this article as: Liu KJ, Jiao RM, Ji J, Yao WW, Han CR, Zhao XY, Zhao JJ. Placebo response in sham acupuncture therapy trials for simple obesity: a systematic review and meta-analysis. J Integr Med. 2025; 23(3): 264-273.
Humans ; Acupuncture Therapy/methods* ; Obesity/therapy* ; Placebo Effect ; Placebos ; Randomized Controlled Trials as Topic

Hallux valgus is a common disorder of the forefeet,and its diagnosis and treatment have always drawn the attention of the practitioners.This article introduced the minimally-invasive diagnosis and treatment system for hallux valgus of integrated traditional Chinese and western medicine,which was established by Professor WEN Jian-Min after more than 40 years of in-depth clinical practice and research based on the theory of yin-yang balance and theory of tendons and bones in traditional Chinese medicine(TCM)and through the combination of modern surgical experience.The minimally-invasive diagnosis and treatment system for hallux valgus embodies the principles of balancing yin and yang,laying equal stress on tendons and bones,unifying the fixation and functional exercises,and treating the fractures and the whole body simultaneously,and includes the key technologies such as minimally-invasive osteotomy for the first metatarsal bone,curtain-wrapped external fixation,perioperative Chinese medicine therapy based on syndrome differentiation,and rehabilitation and nursing of TCM.The system will provide a systematic guide for the standardized minimally-invasive treatment of hallux valgus,and will supply an important approach to the treatment of other orthopedic diseases with integrated traditional Chinese and western medicine.The minimally-invasive diagnosis and treatment system for hallux valgus reflects the scientific research achievements and clinical experience of Professor WEN Jian-Min,which exerts high significance of reference and application value.

Autophagy is an essential cellular metabolic process that involves clearance of damaged organelles and protein aggregates in cells through lysosomes,providing energy for cells,and maintaining cellular tissue homeostasis.Impaired autophagy is closely related to the pathophysiology of a variety of diseases.In the pathogenesis of atherosclerosis(AS),the dysfunction of autophagy of vascular cells plays a crucial role in the formation and progression of AS.The functional status,survival or death of vascular cells,including endothelial cells,vascular smooth muscle cells and macrophages,can influence the formation and stability of plaques,thereby affecting the progression of AS.This review summarizes the relationship between autophagy and AS,and details the impact of autophagy dysfunction on vascular cell function in the process of AS,as well as the role of mitophagy and inflammasome in the development of AS,aiming to provide novel insights for the prevention and treatment of AS.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

Objective:To investigate the association between baseline hemoglobin level and early neurologic deterioration(END)after intravenous thrombolysis in patients with acute ischemic stroke(AIS).Methods:Data of AIS patients who received intravenous thrombolytic therapy at multiple hospitals across the country between January 2017 and July 2020 were collected from the online database Acute Stroke Patients for Stroke Management Quality Evaluation(CASE-Ⅱ,NCT04487340).Binary logistic regression analysis was used to study the factors affecting the occurrence of END after intravenous thrombolytic therapy,and the correlation between baseline hemoglobin level and END was investigated by limiting cubic spline curve analysis.Results:A total of 8162 patients were included.Patients with END had lower baseline hemoglobin levels(136 and 140 g/L,P<0.01)and higher rates of anemia(24.2%and 16.9%,P<0.01)compared with non-END patients.Binary logistic regression analysis showed that baseline hemoglobin level(OR=0.995,95%CI:0.991-0.999,P<0.05)and anemia(OR=1.238,95%CI:1.055-1.454,P<0.01)were independently correlated with the occurrence of END after intravenous thrombolysis in AIS patients.Restricted cubic spline regression showed that there was a U-shaped relationship between hemoglobin level and the risk of END after intravenous thrombolysis in AIS patients(P<0.01),although this relationship was only significant in male patients(P<0.05)and not in female patients(P>0.05).Conclusion:There is a correlation between baseline hemoglobin level and the risk of END in AIS patients after intravenous thrombolysis,especially in male patients,in whom both lower and higher hemoglobin level may increase the risk of END.

Objective:To analyze the epidemiological and clinical characteristics of respiratory syncytial virus (RSV) infection in children in Jiangsu Province from 2014 to 2023.Methods:The acute respiratory infection cases in children aged 0-14 years were selected from outpatient/emergency or inpatient departments in 2 surveillance sentinel hospitals, respectively, in Nanjing, Suzhou and Taizhou of Jiangsu from 1 July 2014 to 31 December 2023, and RSV nucleic acid test was conducted and the intensity of the RSV infection was accessed by WHO influenza epidemiological threshold method, and case information and clinical data were collected. χ2 test was used to compare the differences between groups, and the Bonferroni method was used for pairwise comparisons between groups. Results:In 4 946 cases of acute respiratory infections, the RSV positive rate was 8.21% (406/4 946), and the age M( Q1, Q3) of the cases was 1 (0, 3) years. The RSV positive rate was 10.92% (258/2 362) during 2014-2019 and 6.06% (118/1 948) during 2019-2023, the difference was significant ( χ2=31.74, P<0.001). RSV infection mainly occurred from October to March during 2014-2019, with the incidence peak in December and moderate or higher intensity. The seasonality of RSV infection was not obvious during 2019-2023, with low intensity. The RSV positive rate was highest in children in age group 0- years (17.85%, 151/846), and the positive rate declined gradually with age ( χ2=184.51, P<0.001). The RSV positive rate was higher in inpatient cases (9.84%, 244/2 480) than in outpatient/emergency cases (6.57%, 162/2 466) ( χ2=17.54, P<0.001). In the 155 RSV infection cases with complete clinical data, the clinical symptoms mainly included cough (99.35%, 154/155), fever (55.48%, 86/155), and shortness of breath (45.16%, 70/155). In the cases aged <6 months, the proportion of those with fever was low, but the proportion of those with shortness of breath, transferred to intensive care units, and receiving oxygen therapy were higher (all P<0.05). Children aged <6 months and those with underlying diseases were more likely to have severe RSV infection (all P<0.05). Conclusions:RSV infection in children in Jiangsu Province showed seasonal prevalence in winter from 2014 to 2019. Since 2020, the seasonal characteristics of the epidemic have changed, the epidemic period has been dispersed and the epidemic intensity has decreased. Infants <1 year old were at high risk for RSV infection, and those <6 months old and with underlying diseases might have severe infection.