This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*

Objective To explore the effects of miR-373 and Janus kinase 2/signal transducer and activator of transcription 6 (JAK2/STAT6) signaling pathways on the M2 polarization of tumor associated macrophages (TAM) in rectal cancer. Methods THP-1 cells were induced into M0/M1/M2 macrophages, M0 macrophages were cocultured with Caco-2 cells to obtain TAM, Flow cytometry was used to detect the expression of CD86 and CD206, Real-time quantitative qPCR and Western blot were used to detect miR-373, inducible nitric oxide synthase (iNOS), toll-like receptor 4 (TLR-4), interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), arginase 1 (Arg1), chitinase 3-like 1 (Ym1), resistin like α (Fizz1), IL-10 mRNA and protein levels. TAM were transfected and divided into overexpressing miR-373 group (miR-373-TAM) and control group (miR-NC-TAM), overexpressing miR-373+JAK2-TAM group (miR-373 combined with JAK2-TAM) and control group (miR-373 combined with NC-TAM), and then cocultured with Caco-2 cells. Flow cytometry was used to detect the expression of CD206 in TAM; Real-time quantitative PCR and Western blot were used to detect miR-373, Arg1, Ym1, Fizz1, IL-10, JAK2, STAT6 mRNA and protein levels in TAM; CCK-8 assay, colony formation assay, and Transwell assay were used to detect the proliferation, migration, and invasion ability of Caco-2 cells. Thirty nude mice were randomly divided into Caco-2 cells group, Caco-2 cells combined with miR-NC-TAM group, and Caco-2 cells combined with miR-373-TAM group, with 10 mice in each group. Rats in each group were subcutaneously injected with pure Caco-2 cells, Caco-2 cells combined with TAM, and Caco-2 cells combined with TAM overexpressing miR-373. After 4 weeks of cell inoculation, immunofluorescence staining was used to detect F4/80⁺CD206⁺cells level in tumor tissue; Real-time quantitative PCR and Western blot were used to detect miR-373, JAK2, STAT6, Arg1, Ym1, Fizz1, IL-10 mRNA and protein levels in tumor tissues. Results TAM tended to M2 polarization. After overexpression of miR-373, miR-373 level in TAM was increased, while Arg1, Ym1, Fizz1, IL-10, JAK2, STAT6 mRNA and protein levels were decreased, proliferation, migration, invasion ability of Caco-2 cells were decreased; Overexpression of JAK2 could partially reverse the effect of overexpression of miR-373 on the M2 polarization of TAM and proliferation, migration, invasion ability of Caco-2 cells. TAM could promote tumor growth; Overexpression of miR-373 could inhibit tumor growth and inhibit M2 polarization of TAM. Conclusion miR-373 could inhibit M2 polarization of TAM in rectal cancer, and miR-373 might inhibit proliferation and metastasis of rectal cancer cells by regulating the JAK2/STAT6 pathway.
MicroRNAs/metabolism* ; Humans ; STAT6 Transcription Factor/genetics* ; Signal Transduction/genetics* ; Animals ; Janus Kinase 2/genetics* ; Mice ; Tumor-Associated Macrophages/metabolism* ; Rectal Neoplasms/pathology* ; Caco-2 Cells ; Mice, Nude ; THP-1 Cells ; Mice, Inbred BALB C ; Cell Polarity ; Male

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective:This study aims to construct a monitoring index system for early child development(ECD)that is consistent with China's actual situation,to scientifically and systematically evaluate the level of ECD and service capacity in various regions.Methods:The study was predicated on the theoretical foundation of the Nutrition Care Framework(NCF).Indicators were initially selected through a literature review and focus group interviews.The evaluation indicators were then determined through two rounds of expert consultation utilising the Delphi method.The Priority Sequence Diagram Method(PSDM)was subsequently implemented to determine indicator weights.Results:The final framework encompasses six first-level indicators(good health,adequate nutrition,responsive caregiving,opportunities for learning,security and safety,and demand and investment),12 second-level indicators,and 31 third-level indicators.Conclusion:The ECD index system constructed in this study integrates macro,meso,and micro levels,emphasises cross-sectoral collaboration and attention to child caregivers,and incorporates equity indicators to measure regional disparities.The research outcomes provide a reference for quantitatively assessing the level of ECD and service capacity across various regions in China.By leveraging mechanisms for cross-sectoral collaboration and goal-oriented approaches,the study provides a framework for the allocation of resources to key areas,thus laying the foundation for the sustained implementation and resource assurance of the child-priority development strategy.

Objective To preliminarily explore the safety of collecting colostrum in the third trimester,and to evaluate postpartum breastfeeding in pregnant women with hyperglycemia during pregnancy.Methods Pregnant women with hyperglycemia during pregnancy who had prenatal examinations in Obstetrics and Gynecology Hospital,Fudan University from Jul to Nov 2022 were prospectively divided into the colostrum collection group(n=52)in the third trimester and the control group(n=55)by randomized controlled grouping method.The t-test,χ2 test,Fisher's exact probability method and rank sum test were used for statistical analysis of the data to compare the delivery outcomes,neonatal outcomes and postpartum breastfeeding status between the two groups.Results There were no significant differences in the gestational weeks at delivery,delivery methods,breastfeeding rates at 42 days postpartum and 4 months postpartum between the two groups of pregnant women with hyperglycemia during pregnancy.There were also no significant differences in the Apgar scores at 1 minute and 5 minutes after birth and the neonatal hospitalization rate.The proportion of formula milk as the first supplementary feeding after delivery and the delayed lactation rate at 3 days postpartum in the colostrum collection group were significantly lower than those in the control group(P<0.05).The exclusive breastfeeding rates at 24 hours postpartum and 3 days postpartum in the colostrum collection group were significantly higher than those in the control group(P<0.05).Conclusion Collecting colostrum in the third trimester among pregnant women with hyperglycemia during pregnancy is safe,and it can reduce the rate of supplementary feeding with formula milk after delivery,and increase the exclusive breastfeeding rates at 24 hours postpartum and 3 days postpartum.

Objective:To construct a multi-benefit evaluation index system about the operational quality of medical imaging equipment,so as to optimize the management path for imaging equipment and improve the operational quality of equipment.Methods:A multi-benefit evaluation index system was jointly constructed by the Department of Medical Equipment,Department of Medical Imaging,Benefit Group and Quality Control Group of Medical Affairs Division,Department of Occupational Disease Management of Shanghai Pulmonary Hospital.The multi-criteria decision-making method was used to conduct combined weight analysis and multi-attribute boundary approximate region comparison(MABAC)evaluation for carrying out the evaluation management of operational quality of medical imaging equipment.The used twenty-six medical imaging equipment in the radiology department of hospital from July 2020 to June 2024 were selected.The conventional evaluation method with performance target list was adopted for 25 equipment during the period from July 2020 to June 2022.From July 2022 to June 2024,25 equipment(including used 24 equipment that were evaluated by evaluation method with performance target list and 1 new equipment)were evaluated and managed by adopting multi-benefit evaluation method.The operational quality,medical safety and clinical benefits of medical imaging equipment were compared and analyzed by the two methods.Results:The average utilization rate,qualified rate of quality detection and effective rate of maintenance for medical imaging equipment of using the multi-benefit evaluation method were respectively(96.98±1.42)%,(97.37±1.17)%and(96.05±2.33)%,all of which were higher than those of using evaluation method with performance target list.Its averagely failure frequency was(0.63±0.39)times per quarter,which was lower than that of evaluation method with performance target list,and the differences were statistically significant(t=2.618,3.136,2.848,2.753,P<0.05).The qualified rates of radiation protection devices and radiation protection supplies,and the effective rate of patients'protection of medical imaging equipment of using the multi-benefit evaluation method were higher than those of using evaluation method with performance target list,and the differences were significant(x2=5.657,10.699,10.350,P<0.05).The average values of growth ranges of cost-effectiveness,scientific research achievements,teaching applications and team cultivation about equipment of using the multi-benefit evaluation method were all higher than those of using the evaluation method with performance target list,and the differences were statistically significant(t=5.467,6.236,5.032,4.724,P<0.05),respectively.Conclusion:The application of the multi-benefit evaluation index system for the operational quality of medical imaging equipment can improve the operational quality of equipment,and enhance the medical safety and benefit of operating equipment.

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.

Objective:To compare the efficacy of the transverse process-lateral pedicle approach and curved vertebroplasty in the treatment of osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective cohort study was conducted to analyze the clinical data of 66 patients with OVCF admitted to the Second People′s Hospital of Hefei from December 2021 to June 2023, including 9 males and 57 females aged 60-89 years [(75.6±7.5)years]. The injured segments included T 11 in 17 patients, T 12 in 17, L 1 in 17, and L 2 in 15. Among them, 33 patients underwent vertebroplasty via the transverse process-lateral pedicle approach (lateral approach group), while other 33 patients underwent curved vertebroplasty (curved group). The surgical duration, number of X-ray fluoroscopy, bone cement injection volume, and length of hospital stay were compared between the two groups. Additionally, the restoration efficiency of vertebral height and the correction degree of spinal scoliosis Cobb angle at 2 days postoperatively were compared between the two groups. The changes in serum levels of stress factors including noradrenaline, adrenaline, and cortisol preoperatively and at 2 days postoperatively, the visual analogue scale (VAS) and Oswestry disability index (ODI) preoperatively, at 2 days, 6 months postoperatively, and at the last follow-up were compared between the two groups. The incidence of complications was assessed in the two groups. Results:All the patients were followed up for 12-14 months [(13.2±0.5)months]. The surgical duration and number of X-ray fluoroscopy in the lateral approach group were (30.9±4.1)minutes and (5.9±3.3)times, which were significantly lower than (35.8±3.9)minutes and (9.9±4.4)times in the curved group ( P<0.01). There were no statistically significant differences between the two groups in terms of bone cement injection volume, length of hospital stay, restoration efficiency of vertebral height at 2 days postoperatively, or the correction degree of spinal scoliosis Cobb angle ( P>0.05). The levels of noradrenaline, adrenaline, and cortisol at 2 days postoperatively were (57.3±4.8)ng/ml, (49.9±4.2)ng/ml, (159.3±20.5)nmol/L in the lateral approach group, and (64.3±4.5)ng/ml, (58.3±4.4)ng/ml, (183.5±21.2)nmol/L in the curved group, which were all significantly increased compared with those preoperatively [(42.3±3.5)ng/ml, (38.5±2.8)ng/ml, (128.4±12.3)nmol/L in the lateral approach group and (42.0±3.5)ng/ml, (39.0±3.0)ng/ml, (128.5±12.3)nmol/L in the curved group] ( P<0.01). There were no significant differences between the two groups in terms of the levels of noradrenaline, adrenaline, and cortisol preoperatively ( P>0.05). The levels of noradrenaline, adrenaline, and cortisol at 2 days postoperatively in the lateral approach group were significantly lower than those in the curved group ( P<0.01). The VAS scores for low back pain in the lateral approach group and the curved group were 3(2, 5)points and 5(3, 6)points at 2 days postoperatively, 3(2, 4)points and 3(2, 4)points at 6 months postoperatively, and 2(2, 3)points and 2(2, 4)points at the last follow-up, which were all significantly lower than those preoperatively [7(7, 9)points and 8(6, 9)points] ( P<0.05). Moreover, the VAS scores for low back pain were further decreased over time postoperatively ( P<0.05). The ODI values in the lateral approach group and curved group were (33.4±4.4)% and (33.7±4.3)% at 2 days postoperatively, (23.8±1.6)% and (23.8±1.7)% at 6 months postoperatively, and (15.6±0.9)% and (15.6±0.9)% at the last follow-up, which were all significantly lower than (67.4±4.3)% and (67.5±4.3)% preoperatively ( P<0.05). Moreover, the ODI values were further decreased over time postoperatively ( P<0.05). There were no significant differences between the two groups in terms of the VAS scores for low back pain or ODI values preoperatively, at 2 days, 6 months postoperatively or at the last follow-up ( P>0.05). The complication rate was 12.1% (4/33) in the lateral approach group, which was significantly lower than 51.5% (17/33) in the curved group ( P<0.05). Conclusion:Although both the transverse process-lateral pedicle approach vertebroplasty and the curved vertebroplasty can achieve good therapeutic effects in the treatment of OVCF, the former has shorter surgical duration, fewer times of X-ray fluoroscopy, lower trauma stress levels at 2 days postoperatively, and fewer complications.