Objective: To investigate whether Tuina alleviates fibrotic symptoms in myofascial trigger points (MTrPs) by regulating transforming growth factor (TGF)-β1/Smad3 signaling pathway, thereby deactivating these points. Methods: This study comprised two experimental phases. In phase 1, 27 specific pathogen-free (SPF) grade female Sprague-Dawley (SD) rats were randomized into three groups: control 1, model 1, and Tuina 1 groups. Model 1 and Tuina 1 groups underwent an 8-week MTrPs modeling protocol involving blunt impact and eccentric exercise. After successful modeling, rats in Tuina 1 group received manual pressing on nodules or cord-like taut bands on the medial aspect of the left hindlimb. Pain sensitivity and tissue stiffness were evaluated via pressure pain threshold (PPT) and soft tissue tension (STT). Muscle histopathology and fibrosis were observed using hematoxylin and eosin (HE) and Masson staining. Inflammatory factors in muscle were measured by enzyme-linked immunosorbent assay (ELISA), while immunofluorescence (IF) and Western blot (WB) were used to detect the expression levels of α-smooth muscle actin (α-SMA), collagen Ⅲ, and TGF-β1. In phase 2, 45 SPF female SD rats were randomized into five groups: control 2, model 2, Tuina 2, TGF-β1 inhibitor (TI), and Tuina + TGF-β1 agonist (Tuina + TA) groups. All groups except control 2 underwent standardized MTrPs modeling. Rats in Tuina 2 group received consistent pressing manipulation. TI group received intraperitoneal injections of oxymatrine, while Tuina + TA group received intraperitoneal injections of SRI-011381 hydrochloride followed by the same pressing protocol as Tuina 2 group. WB was used to detect the expression of collagen I, collagen III, TGF-β1, and phosphorylated-Smad3 (p-Smad3)/Smad3. Results: In phase 1, Tuina significantly improved PPT and STT in MTrPs of rats (P < 0.01), reversed pathological damages including disorganized muscle fiber arrangement, abnormal myocyte morphology, and exacerbated fibrosis. In addition, in MTrPs of rats in model 1 group, expression levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and fibrosis markers (α-SMA, collagen I, and collagen III) were upregulated, and all exhibited a significant downward trend after Tuina intervention (P < 0.05 or P < 0.01). This indicates that the therapeutic effects of Tuina are directly associated with reduced local inflammation and fibrosis in MTrPs. In phase 2, compared with model 2 group, rats in TI and Tuina 2 groups had decreased expression levels of TGF-β1 and p-Smad3/Smad3 in MTrPs, alongside reduced levels of inflammatory factors (IL-1β, IL-6, NF-κB, and TNF-α) and fibrosis markers (α-SMA, collagen I, and collagen III) (P < 0.05 or P < 0.01). When co-administered with TGF-β1 agonist, the therapeutic effects of Tuina were significantly attenuated, with rebounded TGF-β1 expression and p-Smad3/Smad3 in local MTrPs, and fibrosis and inflammatory responses were re-exacerbated (P < 0.05 or P < 0.01). Conclusion Tuina can effectively reduce inflammatory responses and fibrosis in MTrPs tissue, and its mechanism is closely related to the inhibition of the TGF-β1/Smad3 signaling pathway, which plays a critical role in Tuina-mediated regulation of MTrPs fibrosis.

OBJECTIVE To formulate Guidelines for the standardized implementation of pharmacist-managed clinics （ 2026 edition ） in response to the challenges faced by such clinics in China， including uneven development， large discrepancies in service specifications， insufficient patient awareness， and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association， the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association， and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association， a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research， current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections： definition and connotation of pharmacist-managed clinics， establishment requirements， implementation and management， post competency， and practical research. Firstly， the definition and connotation included three operational forms of pharmacist-managed clinics （independent mode， physician-pharmacist joint mode， and online pharmacist-managed clinic mode） and classified service modes （specialty-specific， drug-specific， and disease-specific pharmacist-managed clinics）. The establishment requirements were further refined， covering system construction （pharmaceutical service management system， quality control and assessment mechanism）， personnel qualifications （professional credentials， continuing education and professional training， etc）， service recipients， as well as service venues and facilities. Subsequently， the implementation and management of pharmacist-managed clinics were proposed， involving service procedures， intervention measures， documentation and records， patient education and follow-up， humanistic care， as well as risk management and quality control. Finally， post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics， as well as the suggestions on teaching methods； practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment， management， teaching， and research， fill the guideline gap in this field， and can promote the high-quality development of pharmacist-managed clinics.

This study aims to investigate the molecular mechanism by which naringin alleviates cerebral ischemia/reperfusion(CI/R) injury through DRP1/LRRK2/MCU signaling axis. A total of 60 SD rats were randomly divided into the sham group, the model group, the sodium Danshensu group, and low-, medium-, and high-dose(50, 100, and 200 mg·kg~(-1)) naringin groups, with 10 rats in each group. Except for the sham group, a transient middle cerebral artery occlusion/reperfusion(tMCAO/R) model was established in SD rats using the suture method. Longa 5-point scale was used to assess neurological deficits. 2,3,5-Triphenyl tetrazolium chloride(TTC) staining was used to detect the volume percentage of cerebral infarction in rats. Hematoxylin-eosin(HE) staining and Nissl staining were employed to assess neuronal structural alterations and the number of Nissl bodies in cortex, respectively. Western blot was used to determine the protein expression levels of B-cell lymphoma-2 gene(Bcl-2), Bcl-2-associated X protein(Bax), cleaved cysteine-aspartate protease-3(cleaved caspase-3), mitochondrial calcium uniporter(MCU), microtubule-associated protein 1 light chain 3(LC3), and P62. Mitochondrial structure and autophagy in cortical neurons were observed by transmission electron microscopy. Immunofluorescence assay was used to quantify the fluorescence intensities of MCU and mitochondrial calcium ion, as well as the co-localization of dynamin-related protein 1(DRP1) with leucine-rich repeat kinase 2(LRRK2) and translocase of outer mitochondrial membrane 20(TOMM20) with LC3 in cortical mitochondria. The results showed that compared with the model group, naringin significantly decreased the volume percentage of cerebral infarction and neurological deficit score in tMCAO/R rats, alleviated the structural damage and Nissl body loss of cortical neurons in tMCAO/R rats, inhibited autophagosomes in cortical neurons, and increased the average diameter of cortical mitochondria. The Western blot results showed that compared to the sham group, the model group exhibited increased levels of cleaved caspase-3, Bax, MCU, and the LC3Ⅱ/LC3Ⅰ ratio in the cortex and reduced protein levels of Bcl-2 and P62. However, naringin down-regulated the protein expression of cleaved caspase-3, Bax, MCU and the ratio of LC3Ⅱ/LC3Ⅰ ratio and up-regulated the expression of Bcl-2 and P62 proteins in cortical area. In addition, immunofluorescence analysis showed that compared with the model group, naringin and positive drug treatments significantly decreased the fluorescence intensities of MCU and mitochondrial calcium ion. Meanwhile, the co-localization of DRP1 with LRRK2 and TOMM20 with LC3 in cortical mitochondria was also decreased significantly after the intervention. These findings suggest that naringin can alleviate cortical neuronal damage in tMCAO/R rats by inhibiting DRP1/LRRK2/MCU-mediated mitochondrial fragmentation and the resultant excessive mitophagy.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/genetics* ; Flavanones/administration & dosage* ; Rats ; Dynamins/genetics* ; Male ; Brain Ischemia/genetics* ; Protein Serine-Threonine Kinases/genetics* ; Signal Transduction/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage*

The study aims to elucidate the existence forms(original constituents and metabolites) of Notoginseng Radix et Rhizoma in rats and reveal its metabolic pathways. After Notoginseng Radix et Rhizoma was administered orally once a day for seven consecutive days to rats, all urine and feces samples were collected for seven days, while the blood samples were obtained 6 h after the last administration. Using the ultra high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technique, this study identified 6, 73, and 156 existence forms of Notoginseng Radix et Rhizoma in the rat plasma, urine, and feces samples, respectively. Among them, 101 compounds were identified as new existence forms, and 13 original constituents were identified by comparing with reference compounds. The metabolic reactions of constituents from Notoginseng Radix et Rhizoma were mainly deglycosylation, dehydration, hydroxylation, hydrogenation, dehydrogenation, acetylation, and amino acid conjugation. Furthermore, the possible in vivo metabolic pathways of protopanaxatriol(PPT) in rats were proposed. Through comprehensive analysis of the liquid chromatography-mass spectrometry(LC-MS) data, isomeric compounds were discriminated, and the planar chemical structures of 32 metabolites were clearly identified. According to the literature, 48 original constituents possess antitumor and cardiovascular protective bioactivities. Additionally, 32 metabolites were predicted to have similar bioactivities by SuperPred. This research lays the foundation for further exploring the in vivo effective forms of Notoginseng Radix et Rhizoma.
Animals ; Rats ; Drugs, Chinese Herbal/pharmacokinetics* ; Rhizome/metabolism* ; Male ; Rats, Sprague-Dawley ; Chromatography, High Pressure Liquid ; Panax notoginseng/chemistry* ; Tandem Mass Spectrometry ; Feces/chemistry*

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

ObjectiveTo investigate the epidemiological characteristics of hand, foot, and mouth disease (HFMD) in Baoshan District of Shanghai from 2008 to 2023, and to provide scientific evidence for surveillance and standardized management of HFMD. MethodsCase data for HFMD reported in the China Disease Control and Prevention Information System from 2008 to 2023 were collected. Descriptive epidemiological methods were used to analyze the population characteristics, and the Joinpoint regression models were applied to assess the temporal trends of HFMD in Baoshan District. ResultsA total of 43 853 HFMD cases were reported from 2008 to 2023 in Baoshan District, with a male-to-female ratio of 1.50∶1. The majority of cases were children, among which scattered children and preschool children accounted for 54.67% and 36.58%, respectively, with 88.00% occurring in children under 5 years old. The average annual incidence rate was147.22/100 000 individuals. The pathogen detection rate in 2018 was 58.60% (109/186). Prior to 2020, CoxA16 was the predominant strain, while EV71 was not detected after 2019. ConclusionThe incidence of HFMD in Baoshan District of Shanghai was influenced by multiple factors including the inclusion in the notifiable infectious disease surveillance system, the introduction of EV71 vaccination, and the COVID-19 pandemic timeline. Populations characterized by highly mobility and frequent external contacts were at high risk for HFMD in Baoshan District. The predominant circulating strains had shifted sequentially from EV71 and CoxA16 to CoxA6.

Objective: To analyze the results of national external quality assessment (EQA) for transfusion compatibility test from 2018 to 2023, with the aim of providing references for improving laboratory testing quality and ensuring the safety of clinical blood transfusion. Methods: Three EQA programs were conducted annually, each distributing 22 quality assessment samples. Participating transfusion laboratories were required to complete testing within specified deadlines and to submit results along with documentation of testing methodologies, reagents, and equipment used. National Center for Clinical Laboratories (NCCL) conducted statistical analysis of laboratory results, evaluated testing outcomes and related circumstances, and provided feedback to participating laboratories. EQA data from transfusion laboratories across China from 2018 to 2023 were collected and systematically analyzed. Results: From 2018 to 2023, the qualification rates for all five items (ABO forward typing, ABO reverse typing, Rh blood group typing, antibody screening, and cross-matching) were 67.59%, 77.11%, 77.38%, 72.78%, 79.96%, and 85.16%, respectively. The mean qualification rates for ABO forward typing, ABO reverse typing, RhD blood group typing, antibody screening, and cross-matching over the past six years were 96.25%±0.59%, 90.45%±4.52%, 96.05%±0.71%, 90.88%±2.86%, and 88.34%±3.48%, respectively. The qualification rates in 2019, 2020, 2022, and 2023 all showed a stable trend of "blood stations>tertiary hospitals>secondary hospitals". The mean qualification rate of laboratories in secondary hospitals from 2018 to 2023 was significantly lower than those of laboratories in tertiary hospitals and blood stations (P<0.05), while no significant difference was observed between laboratories in tertiary hospitals and blood stations (P>0.05). The micro column agglutination method was the most widely used in all five tests. In the four test items, namely ABO forward typing, ABO reverse typing, antibody screening, and cross-matching, there was a statistically significant difference in the qualification rate of micro column agglutination method compared to other methods (P<0.05). There was a statistical difference in the qualification rate between manual and automated detection using micro column agglutination method in the cross-matching tests (P<0.05), whereas no significant difference was noted for the other test items (P>0.05). Conclusion: From 2018 to 2023, the number of laboratories participating in EQA activities has been increasing year by year, and the qualification rate has shown an overall upward trend. The type of laboratory is a key factor affecting the qualification rate, and the testing capabilities of some laboratories still need to be improved. The micro column agglutination method is widely used in transfusion compatibility tests. The established EQA program effectively monitors quality issues in laboratories, drives continuous improvement, and ensures sustained enhancement of testing standards to safeguard clinical blood safety.

This report describes two cases of severe immune-mediated thrombocytopenia after allogeneic hematopoietic stem cell transplantation (HSCT) who were treated with umbilical cord mesenchymal stem cells (UC-MSCs). Case 1 was a child with severe aplastic anemia who underwent haploidentical bone marrow and peripheral blood HSCT, with a chimerism rate of 99.8% on day +25 and severe immune-mediated thrombocytopenia on day +60. After intravenous immunoglobulin (IVIG) pulse therapy, platelet count increased temporarily but then decreased, while cyclosporine, methylprednisolone, and rituximab had a poor therapeutic effect. Case 2 was a child with Gaucher's disease who underwent unrelated umbilical cord blood HSCT, with a chimerism rate of 96.35% on day +41 and severe immune-mediated thrombocytopenia on day +153. After three sessions of IVIG pulse therapy, the platelet count increased initially but subsequently decreased. Therapies with dexamethasone, prednisone, cyclosporine, and recombinant human thrombopoietin also yielded a poor response. Both children received three sessions of UC-MSCs infusion, and platelet counts increased and were subsequently maintained within the normal range. Case 1 has been followed up for 10 years and remains in disease-free survival. UC-MSCs infusion may be effective for severe immune-mediated thrombocytopenia that is unresponsive to first- and second-line therapies after HSCT and could potentially improve the quality of life and disease-free survival rate.
Child ; Humans ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Mesenchymal Stem Cell Transplantation ; Purpura, Thrombocytopenic, Idiopathic/etiology* ; Thrombocytopenia/therapy* ; Transplantation, Homologous ; Umbilical Cord/cytology*

OBJECTIVE: To investigate the metabolic characteristics of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) in myeloid leukemia by in vitro culture of myeloid leukemia cells and construction of tumor-bearing nude mouse model. METHODS: U937, THP-1, HL60 and K562 cells were cultured in vitro. The cells in logarithmic growth phase (l×10 ⁵ cells/well) were added with ¹⁸F-FDG, and the uptake rate of ¹⁸F-FDG was measured at 15, 30, 60 and 120 min after addation, respectively. The four kinds of cells were inoculated subcutaneously into the hind limbs of nude mice to establish a tumor-bearing nude mouse model. When the tumor size was about 500 mm³, ¹⁸F-FDG was injected through the tail vein of the mice, and positron emission tomography/computed tomography was performed at 60 min after injection. The morphology of tumor-bearing cells was observed by hematoxylin-eosin (HE) staining in serial pathological sections. RESULTS: After co-incubation with ¹⁸F-FDG, the ¹⁸F-FDG uptake rates of U937 cells were significantly higher than THP-1, HL60 and K562 cells at 4 time points (all P <0.05), and THP-1 cells were higher than K562 cells (all P <0.05). The uptake rate of ¹⁸F-FDG by leukemia cells was rapid in the first 60 min, then tended to be stable. Pathological analysis showed that subcutaneous inoculation of U937, THP-1, HL60 and K562 cells could successfully establish tumor-bearing nude mouse models of myeloid leukemia. The ¹⁸F-FDG uptake value in U937 tumor-bearing nude mice was significantly higher than THP-1, HL60 and K562 tumor-bearing nude mice (all P <0.01). The ¹⁸F-FDG uptake values in THP-1 and HL60 tumor-bearing nude mice were significantly higher than that in K562 tumor-bearing nude mice (both P <0.01). CONCLUSION The tumor-bearing nude mouse model of myeloid leukemia can be successfully constructed by subcutaneous inoculation. The ¹⁸F-FDG uptake rate of acute myeloid leukemia (AML) cells is higher in cells cultured in vitro and tumor-bearing nude mouse model. ¹⁸F-FDG may have better clinical application value for AML.
Animals ; Fluorodeoxyglucose F18/metabolism* ; Mice, Nude ; Mice ; Humans ; Leukemia, Myeloid/diagnostic imaging* ; HL-60 Cells ; K562 Cells ; Cell Line, Tumor ; U937 Cells