The study explores the traditional Chinese medicine （TCM） diagnostic and treatment approach to coronary microvascular disease （CMVD） from the perspective of "disharmony of blood collaterals and dysfunction of qi transformation". It is proposed that the core pathogenesis of CMVD lies in these two mechanisms. From an integrative medicine perspective， different CMVD types are analyzed based on their specific pathogenesis. Through clinical practice， four targeted treatment methods， i.e. warming， unblocking， tonifying， and activating， are formulated. CMVD caused by atherosclerosis is primarily associated with myocardial ischemia， myocardial infarction， and coronary revascularization， with corresponding pathological mechanisms of latent pathogenic obstruction， toxic accumulation in the collaterals， and deficiency with collateral stasis. The disease progression exhibits characteristics of correlation， staging， and transformation. Accordingly， treatment principles include warming to assist qi transformation， unblocking obstruction and dispelling turbidity， activating to disperse toxic stasis and invigorate collaterals， and tonifying to eliminate stasis and nourish collaterals. For CMVD unrelated to atherosclerosis， attention should be paid to the underlying disease， analyzing the main syndromes of blood and collateral disharmony. An approach combining disease-syndrome differentiation with blood and collateral regulation is emphasized for precise treatment.

OBJECTIVES: To investigate the effect of ecliptasaponin A (ESA) for alleviating dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD) in mice and the underlying mechanism. METHODS: Twenty-four male C57BL/6 mice (8-10 weeks old) were equally randomized into control group, DSS-induced IBD model group, and DSS+ESA (50 mg/kg) treatment group. Disease activity index (DAI), colon length and spleen index of the mice were measured, and intestinal pathology was examined with HE staining. The expressions of inflammatory mediators (TNF-α, IL-6, and iNOS) in the colon mucosa were detected using ELISA and RT-qPCR, and intestinal barrier integrity was assessed using AB-PAS staining and by detecting ZO-1 and claudin-1 expressions using immunofluorescence staining and Western blotting. In cultured RAW264.7 macrophages, the effects of treatment with 50 μmol/L ESA, alone or in combination with 20 μmol/L RO8191 (a JAK2/STAT3 pathway activator), on M1 polarization of the cells induced by LPS and IFN-γ stimulation and expressions of JAK2/STAT3 pathway proteins were analyzed using flow cytometry and Western blotting. RESULTS: In the mouse models of DSS-induced IBD, ESA treatment significantly alleviated body weight loss and colon shortening, reduced DAI, spleen index and histological scores, and ameliorated inflammatory cell infiltration in the colon tissue. ESA treatment also suppressed TNF‑α, IL-6 and iNOS expressions, protected the goblet cells and the integrity of the mucus and mechanical barriers, and upregulated the expressions of ZO-1 and claudin-1. ESA treatment obviously decreased CD86⁺ M1 polarization in the mesenteric lymph nodes of IBD mice and in LPS and IFN-γ-induced RAW264.7 cells, and significantly reduced p-JAK2 and p-STAT3 expressions in both the mouse models and RAW264.7 cells. Treatment with RO8191 caused reactivation of JAK2/STAT3 and strongly attenuated the inhibitory effect of ESA on CD86⁺ polarization in RAW264.7 cells. CONCLUSIONS ESA alleviates DSS-induced colitis in mice by suppressing JAK2/STAT3-mediated M1 macrophage polarization and mitigating inflammation-driven intestinal barrier damage.
Animals ; Mice ; Janus Kinase 2/metabolism* ; STAT3 Transcription Factor/metabolism* ; Mice, Inbred C57BL ; Male ; Dextran Sulfate ; Macrophages/cytology* ; Colitis/metabolism* ; Saponins/pharmacology* ; Signal Transduction/drug effects* ; RAW 264.7 Cells ; Triterpenes/pharmacology* ; Interleukin-6/metabolism*

OBJECTIVES: To investigate the mechanism through which pinostrobin (PSB) alleviates dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: C57BL/6 mice were randomized into control group, DSS model group, and PSB intervention (30, 60, and 120 mg/kg) groups. Colitis severity of the mice was assessed by examining body weight changes, disease activity index (DAI), colon length, and histopathology. The expressions of tight junction proteins ZO-1 and claudin-1 in the colon tissues were examined using immunofluorescence staining, and macrophage infiltration and polarization were analyzed with flow cytometry. ELISA and RT-qPCR were used for detecting the expressions of inflammatory factors (TNF‑α and IL-6) and chemokines (CCL₂, CXCL₁₀, and CX₃CL₁) in the colon tissues, and PI3K/AKT phosphorylation levels were analyzed with Western blotting. In cultured Caco-2 and RAW264.7 cells, the effect of PSB on CCL₂-mediated macrophage migration was assessed using Transwell assay. Network pharmacology analysis was performed to predict the key pathways that mediate the therapeutic effect of PSB. RESULTS: In DSS-induced mouse models, PSB at 60 mg/kg optimally alleviated colitis, shown by reduced weight loss and DAI scores and increased colon length. PSB treatment significantly upregulated ZO-1 and claudin-1 expressions in the colon tissues, inhibited colonic macrophage infiltration, and promoted the shift of macrophage polarization from M1 to M2 type. In cultured intestinal epithelial cells, PSB significantly inhibited PI3K/AKT phosphorylation and suppressed chemokine CCL₂ expression. PSB treatment obviously blocked CCL₂-mediated macrophage migration of RAW264.7 cells, which could be reversed by exogenous CCL₂. Network pharmacology analysis and rescue experiments confirmed PI3K/AKT and CCL₂ signaling as the core targets of PSB. CONCLUSIONS PSB alleviates DSS-induced colitis in mice by targeting intestinal epithelial PI3K/AKT signaling, reducing CCL₂ secretion, and blocking macrophage chemotaxis and migration, highlighting the potential of PSB as a novel natural compound for treatment of inflammatory bowel disease.
Animals ; Mice ; Mice, Inbred C57BL ; Phosphatidylinositol 3-Kinases/metabolism* ; Colitis/drug therapy* ; Dextran Sulfate ; Proto-Oncogene Proteins c-akt/metabolism* ; Macrophages ; Chemokine CCL2/metabolism* ; Humans ; Signal Transduction/drug effects* ; Caco-2 Cells ; RAW 264.7 Cells ; Epithelial Cells/drug effects* ; Intestinal Mucosa/metabolism*

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:To synthesize 18F labeled PET imaging probe based on giredestrant (GDC-9545), an estrogen receptor α (ERα) degrader and antagonist, and evaluate its ERα-targeting properties. Methods:The precursor-GDC (PGDC), GDC and 18F-GDC were synthesized. The radiochemical yields, radiochemical purity, specific activity, lipid water partition coefficient log P, and stability of 18F-GDC were determined. Cellular uptake and blocking assays of 18F-GDC were performed using ERα high-expressing MCF-7 cells and ERα low-expressing MDA-MB-231 cells. MCF-7 and MDA-MB-231 tumor-bearing mice were constructed and microPET imaging was performed. The biodistribution of 18F-GDC in MCF-7 tumor-bearing mice was studied. Data were analyzed by using two-way repeated measures analysis of variance and Bonferroni correction method. Results:PGDC and GDC were successfully prepared with the purity more than 95%. 18F-GDC was successfully synthesized with the labeling yield of (11.25±3.18)%, radiochemical purity more than 98%, specific activity of (140.66±17.20)GBq/μmol and lipid water partition coefficient log P of 2.12±0.13. 18F-GDC was stable in PBS or mouse serum, with the radiochemical purity still more than 98% after 2 h of incubation. After incubation for 60 and 120min, the uptakes of 18F-GDC in MCF-7 cells were significantly higher than those in MDA-MB-231 cells ( F values: 113.78, 369.70, P values: 0.002, 0.001 (Bonferroni correction method)), and could be blocked by GDC. 18F-GDC had a high uptake in MCF-7 tumors and could be blocked by GDC. Tumor uptake at 60 min post-injection was (7.23±0.74) percentage activity of injection dose per gram of tissue (%ID/g) and the tumor/muscle uptake ratio was 2.83±0.29 in MCF-7 tumors, while 18F-GDC had a lower uptake in MDA-MB-231 tumors, with (2.01±0.46)%ID/g at 60min post-injection, and a tumor/muscle uptake ratio of 0.96±0.22 ( F values: 77.28, 55.44, P values: 0.002, 0.006 (Bonferroni correction method)). 18F-GDC was mainly distributed in MCF-7 tumors and organs including heart, liver, spleen, kidney, stomach and intestines. Conclusions:18F-GDC is successfully synthesized, with high radiochemical purity and stability, and can concentrate in the ERα-overexpressing cancer cells and lesion area of xenograft tumor mouse. It presents good image contrast in PET imaging, indicating excellent diagnostic performance.

Objective:To design and synthesize a 18F-labeled small molecule PET imaging probe targeting carbonic anhydrase Ⅸ (CAⅨ), named as 18F-single-acetazolamide (SAZ), and to evaluate its biological properties preliminarily. Methods:Acetazolamide was used as raw material to synthesize the precursor SAZ, and the target probe 18F-SAZ was obtained through nucleophilic substitution and other reactions. The radiochemical yield, radiochemical purity, specific activity, lipid water partition coefficient log P, and stability of 18F-SAZ were determined. Cancer cell lines OS-RC-2 (CAⅨ-positive) and HCT116 (CAⅨ-negative) were used for cell uptake experiments, and corresponding tumor-bearing mice were constructed for microPET imaging. Biodistribution of the probe in OS-RC-2 tumor-bearing mice was analyzed. The difference among groups was analyzed by repeated measures analysis of variance and Bonferroni method. Results:The probe 18F-SAZ was successfully prepared with the labelling yield of (5.60±0.51)%, specific activity of (7.90±0.62)MBq/nmol, radiochemical purity more than 99%, and the lipid water partition coefficient log P of -0.38±0.01. After incubation with PBS or mouse serum for 4 h, the radiochemical purity was still more than 99%. The uptake of 18F-SAZ in OS-RC-2 cells reached (1.47±0.24) percentage of the added radioactivity dose (%AD) at 30min, which was significantly higher than the uptake in the blocked group and that in HCT116 cells ((0.60±0.07)%AD, (0.50±0.05)%AD; F=24.31, P values: 0.012, 0.013 (Bonferroni correction method)). The results of microPET imaging showed that the uptake of 18F-SAZ in OS-RC-2 tumors reached the maximum at 30min ((2.92±0.07) percentage activity of injection dose per gram of tissue (%ID/g)), while the maximum uptakes in the blocked group and HCT116 tumors were only (1.36±0.02) and (1.12±0.07)%ID/g, respectively. 18F-SAZ was mainly distributed in tumors and organs including kidney, intestine, liver, stomach in OS-RC-2 tumor-bearing mice. Conclusions:The probe 18F-SAZ is successfully synthesized. It has high radiochemical purity and good stability in vitro, and can specifically target tumor cells with high expression of CAⅨ. It is expected to be a new CAⅨ-targeting PET imaging probe.

Deep brain stimulation(DBS)has witnessed rapid advancement as a neurosurgical intervention over the past four decades,addressing movement disorders and a spectrum of neuropsychiatric conditions.Notably,subthalamic nucleus deep brain stimulation(STN-DBS)is widely implemented in the management of Parkinson's disease(PD)patients experiencing refractory motor fluctuations and complications,and has shown promise in ameliorating non-motor symptoms(NMS).However,the long-term efficacy of STN-DBS on NMS remains a subject of scholarly discourse.This review endeavors to synthesize current knowledge regarding the long-term impacts,underlying mechanisms,and future research directions of STN-DBS in the context of NMS in Parkinson's disease.

OBJECTIVE: To elucidate the rules of temporal and spatial variations in distal skin potential at Hegu (LI4) under different stimulation modes by extracting nonlinear characteristic parameters from array multichannel data and adopting multivariate statistical analysis. METHODS: Seven healthy subjects were selected and the surface potential at the left Quchi (LI11) was collected using 14×9 array multichannel electrodes. Using Hegu (LI4) on the left as the stimulation point, four stimulation modes were applied, i.e. being quiescent, point pressing, moxibustion, and manual needling manipulation. Electrical signals were collected for 30 s in each mode, with a 5-min interval between operations, and a sampling frequency of 16 384 Hz. The data was denoised using ensemble empirical mode decomposition (EEMD), and sample entropy (SaEn) features were extracted. Statistical analysis was conducted on these data using factor analysis and multivariate analysis of variance. RESULTS: The SaEn values of most electrode channels were higher under point pressing, moxibustion and manual needling manipulation compared with those under quiescent condition. Under manual needling manipulation, the SaEn value of the electrode channel reached the peak in the first time interval (1-5 s) and it was declining thereafter. Factor analysis showed that the specificity of activation channels was concentrated at the left Quchi (LI11) (loading capacity ≥0.90). Analysis of variance indicated that the significant differences were presented in average sample entropy (SaEn()) values of activation channels among different stimulation modes at Hegu (LI4) (P<0.001), but there was no statistically significant interaction effect between groups and time intervals (P>0.05). CONCLUSION Through nonlinear characteristic parameter extraction and multivariate statistical analysis, we have uncovered the complex temporal and spatial dynamical rules of distal skin potential at Hegu (LI4) under various stimulation modes and successfully identified the specific activation characteristics at Quchi (LI11).
Humans ; Moxibustion ; Acupuncture Points ; Male ; Adult ; Female ; Young Adult ; Acupuncture Therapy/instrumentation*