OBJECTIVE: To investigate the factors affecting ferric chloride (FeCl₃) - induced carotid artery thrombosis model experiment. METHODS: After the common carotid artery was damaged by FeCl₃, the injured vessels were dissected for fixation, embedding, frozen section, and then processed HE staining. The carotid thrombus area ratio was calculated. We examined the effect of FeCl₃ concentration (5%, 10% and 15%), reaction time (2, 4 and 6 min), and recipient mouse age (4-5, 6-8 and 10 weeks) on the formation and stability of arterial thrombosis model. The model was injected through the post-glomus venous plexus of mouse eyeball with 0.075 μg/g and 0.1 μg/g R300 to verify the accuracy of the FeCl₃-induced model on thrombus formation by adjusting the platelet number. RESULTS: HE staining showed that thrombus formation induced by 10% and 15% FeCl₃ was more stable, dense and larger than 5% FeCl₃-induced thrombosis. 10% FeCl₃ induced the formation of dense and large thrombosis after 4 and 6 minutes of vascular endothelium injury, while the thrombosis induced for 2 minutes were looser and smaller in area. Mouse age can not affect thrombus formation and stability, because there were no significant differences in the formation of dense thrombus and thrombus area induced by 10% FeCl₃ among three different age groups of mice. CONCLUSION Many factors affect the formation and stability of arterial thrombosis model induced by FeCl₃. This optimal experimental conditions for construction of a stable carotid artery thrombosis model are 10% FeCl₃, 4 minutes for injury, and 6-8 week old mice.
Animals ; Mice ; Ferric Compounds/adverse effects* ; Chlorides ; Disease Models, Animal ; Carotid Artery Thrombosis/chemically induced* ; Male

Toxoplasma gondii is a single-celled parasite that infects nearly all warm-blooded animals, including humans (Montoya and Liesenfeld, 2004). It occurs worldwide and can persist for a lifetime in mammals. Humans get infected by eating undercooked meat of animals containing the tissue cysts of this parasite. In immune-competent individuals, T. gondii infection usually does not cause significant clinical symptoms, whereas in pregnant or immunocompromised individuals, T. gondii infection (toxoplasmosis) can cause more serious problems like abortion and even death (Dunn et al., 1999; Wang et al., 2017). A combination of pyrimethamine and sulfadiazine is usually used to treat toxoplasmosis, although it is generally inefficient and causes side effects (Alday and Doggett, 2017). Worse still, there is a lack of vaccines to prevent T. gondii infection in humans or animals.
Toxoplasma/enzymology* ; Animals ; Humans ; Toxoplasmosis ; Mitochondria/enzymology* ; Protozoan Proteins/metabolism*

OBJECTIVE: Diabetes-induced gastrointestinal (GI) motility disorders are increasingly prevalent. Damage to the enteric nervous system (ENS), composed primarily of enteric neurons and glial cells, is an essential mechanism involved in these disorders. Although electroacupuncture (EA) has shown the potential to mitigate enteric neuronal loss, its mechanism is not fully understood. Additionally, the effects of EA on enteric glial cells have not been investigated. Enteric neural precursor cells (ENPCs) contribute to the structural and functional integrity of the ENS, yet whether EA enhances their differentiation into enteric neurons and glial cells remains unexplored. This study investigates whether EA promotes ENS repair through enhancing ENPC-derived neurogenesis and gliogenesis and elucidates the potential molecular mechanisms involved. METHODS: Transgenic mice were used to trace Nestin⁺/nerve growth factor receptor (Ngfr)⁺ ENPCs labeled with green fluorescent protein (GFP) in vivo. Mice were randomly divided into four groups: control, diabetes mellitus (DM), DM + sham EA, and DM + EA. The effects of EA on diabetic mice were evaluated by GI motility, ENS structure, and ENPC differentiation. Glial cell line-derived neurotrophic factor (GDNF)/Ret signaling was detected to clarify the underlying molecular mechanisms. RESULTS: EA alleviated diabetes-induced GI motility disorders, as indicated by reduced whole gut transit time, shortened colonic bead expulsion time, and enhanced smooth muscle contractility. Furthermore, EA attenuated diabetes-induced losses of enteric neurons and glial cells, thereby restoring ENS integrity. Notably, EA reversed the diabetes-induced decrease in ENPCs and significantly increased the absolute number and the proportion of ENPC-derived enteric neurons. However, immunofluorescence analyses revealed no colocalization between EA-induced glial fibrillary acidic protein⁺ glial cells and GFP-labeled ENPCs. Mechanistically, GDNF/Ret signaling was elevated in intestinal tissues and upregulated in ENPCs in EA-treated diabetic mice. CONCLUSION EA facilitates ENS repair by promoting Nestin⁺/Ngfr⁺ ENPC differentiation into enteric neurons via upregulation of GDNF/Ret signaling, and driving enteric gliogenesis from non-Nestin⁺/Ngfr⁺ ENPCs. These findings highlight EA's role in ameliorating diabetes-induced GI dysmotility through ENPC-derived ENS restoration. Please cite this article as: Guo JL, Liu S, Ding SJ, Yang X, Du F. Electroacupuncture at ST36 improves gastrointestinal motility disorders by promoting enteric nervous system regeneration through GDNF/Ret signaling in diabetic mice. J Integr Med. 2025; 23(5):548-559.
Animals ; Electroacupuncture ; Enteric Nervous System/physiology* ; Gastrointestinal Motility/physiology* ; Glial Cell Line-Derived Neurotrophic Factor/metabolism* ; Diabetes Mellitus, Experimental/therapy* ; Signal Transduction ; Mice ; Gastrointestinal Diseases/physiopathology* ; Proto-Oncogene Proteins c-ret/metabolism* ; Mice, Transgenic ; Male ; Nerve Regeneration ; Neural Stem Cells ; Mice, Inbred C57BL ; Acupuncture Points

Wastewater-based epidemiology has emerged as a transformative surveillance tool for estimating substance consumption and monitoring disease prevalence, particularly during the COVID-19 pandemic. It enables the population-level monitoring of illicit drug use, pathogen prevalence, and environmental pollutant exposure. In this perspective, we summarize the key challenges specific to the Chinese context: (1) Sampling inconsistencies, necessitating standardized 24-hour composite protocols with high-frequency autosamplers (≤ 15 min/event) to improve the representativeness of samples; (2) Biomarker validation, requiring rigorous assessment of excretion profiles and in-sewer stability; (3) Analytical method disparities, demanding inter-laboratory proficiency testing and the development of automated pretreatment instruments; (4) Catchment population dynamics, reducing estimation uncertainties through mobile phone data, flow-based models, or hydrochemical parameters; and (5) Ethical and data management concerns, including privacy risks for small communities, mitigated through data de-identification and tiered reporting platforms. To address these challenges, we propose an integrated framework that features adaptive sampling networks, multi-scale wastewater sample banks, biomarker databases with multidimensional metadata, and intelligent data dashboards. In summary, wastewater-based epidemiology offers unparalleled scalability for equitable health surveillance and can improve the health of the entire population by providing timely and objective information to guide the development of targeted policies.
China/epidemiology* ; Humans ; Wastewater/analysis* ; COVID-19/epidemiology* ; Public Health ; Wastewater-Based Epidemiological Monitoring ; SARS-CoV-2

Objective:To learn about the single nucleotide polymorphism (SNP) population structure and regional distribution characteristics of Yersinia pestis in the natural focus of plague in Qinghai-Tibet Plateau. Methods:A total of 319 representative strains of Yersinia pestis isolated from natural focus of plague in Qinghai-Tibet Plateau from 1954 to 2020 were selected, and 2 298 SNP loci included in the global Yersinia pestis phylogenetic tree were compared by whole genome sequencing technology. MEGA 6.0 software was used to construct phylogenetic trees of 319 strains of Yersinia pestis from Qinghai-Tibet Plateau, determine the SNP population structure of Yersinia pestis in the focus, and describe its regional distribution characteristics. Results:The 319 strains of Yersinia pestis isolated from Qinghai-Tibet Plateau natural plague foci were distributed in 5 clades, namely 1.IN, 2.ANT, 3.ANT, 0.PE and 2.MED. The 1.IN clade contained 209 strains (65.52%, 209/319), which was the dominant population of strains in Qinghai Province, accounting for 90.51% (143/158). The 2.ANT clade contained 83 strains (26.02%, 83/319), which was the dominant population in Tibet Autonomous Region, accounting for 67.24% (78/116). The 3.ANT, 0.PE, and 2.MED clades contained 12 (3.76%, 12/319), 9 (2.82%, 9/319) and 6 strains (1.88%, 6/319), respectively, which were scattered in Qinghai Province, Gansu Province, Sichuan Province, Tibet Autonomous Region, and Xinjiang Uygur Autonomous Region under the jurisdiction of Qinghai-Tibet Plateau. Conclusion:The SNP population structure of Yersinia pestis in natural focus of plague in Qinghai-Tibet Plateau is relatively rich, and the strains are distributed in 5 clades: 1.IN, 2.ANT, 3.ANT, 0.PE and 2.MED, showing the distribution characteristics of specific regions.

Objective:To introduce a surgical technique of " short distances and multi-segment" buried-guiding suture method and its effects in the surgery of early descent of prosthesis after augmentation mammaplasty.Methods:From August 2019 to January 2022, 15 cases of early descent of prosthesis after augmentation mammaplasty due to axillary approach breast augmentation for micromastia were admitted to the Plastic Surgery Department of Sichuan Provincial People′s Hospital, aged 23-35 years (27.3±3.6) and duration of dislocation from 16 to 35 days (23.8±5.8). There were 12 patients showed unilateral prosthesis drops and 3 patients showed bilateral prosthesis drops. " Short distances and multi-segment" buried-guiding suture method was used to solve the problem, i. e., 2-0 non-absorbable sutures were used to eliminate the lower pole of prosthetic cavity with " short distances and multi-segment" sutures. The distance from the nipple to the midline of the sternum, the distance from the sternotomy to the nipple, the distance from the nipple to the inframammary fold and the distance from the midclavicular point to the inframammary fold were measured bilaterally before and after surgery, and statistical analysis was performed to evaluate the efficacy of the " short distances and multi-segment" buried-guiding suture method for early descent of prosthesis after breast augmentation.Results:All incisions healed by first intention without complications such as hematoma, infection, or scar hyperplasia. 15 patients were followed up for 6-12 months (8.0±1.9). 14 patients were satisfied with the results after surgery, and 1 patient received satisfactory results after secondary surgery. The distance from nipple to inframammary fold was shortened by 0.8-1.4 cm after surgery (1.2±0.2), and the distance from mid-clavicle to inframammary fold was shortened by 1.0-1.6 cm (1.3±0.4), and the differences were statistically significant as compared with the values before surgery ( t=31.17, P<0.05; t=33.78, P<0.05). After surgery, the change in the distance from nipple to sternal was 0.1-0.3 cm (0.16±0.10), and the change in the distance from sternal notch to nipple was 0-0.2 cm (0.12±0.10), and the differences were not statistically significant ( P>0.05). Conclusions:With the advantages of simple operation, little trauma and no additional incision, the " short distance and multi-stage" buried-guiding suture method in the surgery of early descent of prosthesis after augmentation mammaplasty is worthy of clinical application.

Objective:To investigate how reactive oxygen species(ROS)regulates the signal transduction of platelet activation and apoptosis,and to explore the relationship between platelet activation and apoptosis.Methods:Platelets were directly stimulated with thrombin or pretreated with ROS inhibitor N-acetylcysteine(NAC)before being stimulated with thrombin,and then flow cytometry was used to detect the effects of thrombin and NAC on P-selectin expression,αⅡbβ3 activation,mitochondrial membrane potential depolarization,phosphatidylserine(PS)externalization,ROS expression and platelet aggregation.Results:Thrombin could induce the production of ROS in platelets in a concentration-and time-dependent manner.0.01 U thrombin induced ROS-dependent high degree of integrin αⅡbβ3 activation,P-selectin expression,and platelet aggregation.The platelets induced by different concentration gradients of thrombin exhibited ROS-dependent mitochondrial membrane potential depolarization and PS externalization in platelets.After induction with thrombin for 30 min,the activation of integrin αⅡbβ3 in platelets reached its maximum level,and after 60 minutes,the depolarization of mitochondrial membrane potential in platelets reached its maximum level.However,the expression of P-selectin,depolarization of mitochondrial membrane potential,and platelet aggregation function were all inhibited to a certain extent when the platelets were pretreated with ROS inhibitor NAC and then induced with thrombin.Conclusion:When platelets are induced by thrombin,ROS first regulates the activation of platelets,and then regulates the apoptosis of platelets.Both platelet activation and apoptosis depend on the production of ROS in platelets,and the signals of activation and apoptosis occur orderly.Inhibiting the ROS signal in platelets can effectively inhibit the activation and apoptosis of platelets.

BACKGROUND: Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months. RESULTS: Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group. CONCLUSION: Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state. TRIAL REGISTRATION Chictr.org, ChiCTR2000039799.
Humans ; Quality of Life ; China ; Arthritis, Rheumatoid/drug therapy* ; Piperidines/therapeutic use* ; Treatment Outcome ; Antirheumatic Agents/therapeutic use* ; Pyrroles/therapeutic use*

Taking the recommendations development of the World Federation of Acupuncture-Moxibustion Societies (WFAS) standard Clinical Practice Guideline for Female Urinary Incontinence as an example, this study analyzed the consensus expert composition, specific consensus process, and results in the development of the guideline's recommendations. It systematically examined the advantages of using the modified Delphi method in the formation of recommendations for acupuncture and moxibustion clinical practice guideline, with the aim of providing reference for the development of acupuncture and moxibustion guidelines in the same field.
Female ; Humans ; Acupuncture ; Acupuncture Therapy ; Delphi Technique ; Moxibustion

Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.