Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and functional impairment. Angiogenesis plays a key role in the pathological progression of RA with dysfunction of endothelial cells to promote synovial inflammation, sustain pannus formation, subsequently leading to joint damage. Colquhounia Root Tablets (CRT), a Chinese patent drug, has shown a satisfying clinical efficacy in treating RA, while the underlying mechanism by which CRT inhibits RA-associated angiogenesis remains unclear. In this study, we applied a research approach combining transcriptomic data analysis, bio-network mapping, and in vivo and in vitro experiments to explore the molecular mechanisms of CRT in suppressing angiogenesis in RA. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences (ratification number: IBTCMCACMS21-2307-06). Network analysis identified that key genes such as nucleotide-binding oligomerization domain-containing protein 2 (NOD2), SMAD family member 3 (SMAD3), and vascular endothelial growth factor A (VEGFA) significantly enriched in pathways related to NOD-like receptor signaling and VEGF signaling, indicating that CRT may inhibit angiogenesis by regulating vascular endothelial cell function with modulating angiogenesis-related pathways. In vivo data showed that CRT significantly reduced the positive expression of CD31 and VEGF in the ankle joint of adjuvant-induced arthritis (AIA) rats. In vitro data further confirmed that CRT effectively inhibited VEGF-induced migration, invasion, and tube formation in HUVECs, while significantly reduced the expression of angiogenesis-related factors VEGF/CD31/Ang-1, as well as the positive expression of VEGF and CD31 in HUVECs. Furthermore, CRT markedly decreased the protein expression of NOD2, VEGFA, and SMAD3. In conclusion, these findings indicate that CRT may inhibit the RA-related angiogenesis by targeting the NOD2/SMAD3/VEGF signaling axis to improve endothelial cell function, enriching the scientific connotation of CRT in inhibiting pathological angiogenesis in RA and also offer new insights for clinical prevention and treatment of RA.

This paper summarizes Professor HAN Mingxiang's clinical experience in treating chronic obstructive pulmonary disease （COPD）. He believes that the key pathomechanism of COPD in the acute exacerbation stage is the invasion of external pathogens triggering latent illness， while lung qi deficiency is the primary mechanism in the stable stage. The core pathological factors throughout disease progression are deficiency， phlegm， and blood stasis. Treatment emphasizes a staged and syndrome-based approach. During the acute exacerbation stage， for wind-cold invading the lung syndrome， the self-formulated Sanzi Wenfei Decoction （三子温肺汤） is used to relieve the exterior， dispel cold， warm the lung， and resolve phlegm. For phlegm-dampness obstructing the lung syndrome， Huatan Jiangqi Fomulation （化痰降气方） is prescribed to warm the lung， transform phlegm， descend qi， and calm wheezing. For phlegm-heat obstructing the lung syndrome， Qingfei Huatan Fomulation （清肺化痰方） is applied to clear heat， resolve phlegm， moisten the lung， and stop coughing. For phlegm and blood stasis interlocking syndrome， Qibai Pingfei Fomulation （芪白平肺方） is used to tonify qi， resolve phlegm， and activate blood circulation to remove stasis. During the stable stage， for lung qi deficiency syndrome， Shenqi Wenfei Decoction （参芪温肺汤） is employed to warm the lung， tonify qi， resolve phlegm， and eliminate turbidity. For lung-spleen qi deficiency syndrome， Shenqi Buzhong Decoction （参芪补中汤） is utilized to strengthen the spleen， tonify qi， and reinforce metal （lung） from earth （spleen）. For lung-kidney deficiency syndrome， Shenqi Tiaoshen Fomulation （参芪调肾方） is prescribed to tonify the lung， warm yang， and regulate kidney function to calm wheezing. These strategies provide insights into the traditional Chinese medicine treatment of COPD.

To investigate the therapeutic effect and related mechanisms of hordenine on ovalbumin (OVA)-induced allergic rhinitis (AR) in rats, HE and AB-PAS staining were used to detect the improvement of pathological damage to the nasal mucosa induced by hordenine. ELISA was employed to detect the effect of hordenine on OVA-sIgE in serum and IL-4 in the nasal mucosa supernatant of rats. IHC and Western blot experiments were undertaken to examine the effect of hordenine on Th1/Th2 cell balance. Bioinformatics analysis was performed to predict pathways, which were verified by in vivo and in vitro experiments. The experimental results showed that hordenine could alleviate the behavioral manifestations of OVA-induced AR rats, alleviate nasal mucosal pathological damage caused by AR, and reduce the secretion of OVA-sIgE and IL-4. In addition, hordenine could regulate the Th1/Th2 balance. Bioinformatics analysis results showed that the potential pathway of action of hordenine on AR was the phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway. The in vivo experimental results showed that the expression of PI3K and p-Akt proteins in the nasal mucosa of the model group rats was significantly increased (P < 0.01), and that the protein expression level was significantly decreased after the administration of hordenine, which was also confirmed by an in vitro experiment. This study suggests that hordenine may regulate Th1/Th2 cell balance through the PI3K/Akt signaling pathway, thereby exerting an alleviating effect on OVA-induced AR.

OBJECTIVE To analyze the current status and challenges in importing rare disease drugs in China， providing references for optimizing the import process and improving relevant policies. METHODS Questionnaires and interviews were conducted with stakeholders involved in rare disease drug importation， including government departments， multinational pharmaceutical enterprises， healthcare institutions， and patient organizations. This explored the current situation and challenges encountered by each party. Expert opinions were synthesized to propose improvement suggestions. RESULTS A questionnaire survey of representatives from 25 multinational pharmaceutical companies in the rare disease field revealed that these companies had a strong willingness to import rare disease drugs， with 58.33% of them practicing diverse import models. However， significant challenges hindered this process， including unclear regulations （54.17%）， complex approval procedures （45.83%）， and excessively long approval cycles （41.67%）， negatively impacting their motivation. Meanwhile， interviews with 13 experts from government departments， healthcare institutions， pharmaceutical enterprises， and patient organizations identified deficiencies in policy design， approval processes， sampling inspection costs， and communication efficiency with regulators. Additionally， the drug import model in special medical zones also required improvement. CONCLUSIONS The importation of rare disease drugs in China faces challenges such as incomplete policies， inflexible regulatory mechanisms， and insufficient communication channels. It is recommended to enhance the rare disease definition criteria， optimize import incentive policies， and refine regulatory models， so as to further optimize the import process of rare disease drugs and improve relevant policies.

ObjectiveTo explore the impacts of material type and loading volume of rigid containers on the hydrogen peroxide low temperature plasma sterilization of thoracoscopic instruments, to identify the best rigid containers and loading volume of thoracoscopic instruments. MethodsThoracoscopic instruments sterilized by STERRAD^® 100NX hydrogen peroxide low temperature plasma in Shanghai Pulmonary Hospital affiliated to Tongji University from August to September 2024 were selected as the research items. According to the material of rigid containers, the instruments were divided into polyethylene case group (A), stainless steel case group (B) and silicone resin case group (C). In terms of the loading volume, the rigid containers were divided into (loading capacity <80%) groups of 8, 10 and 12 instruments. The results of physical monitoring, the first type of chemical indicator card monitoring, and the five types of card luminal chemical process challenge device (PCD) monitoring of the 9 groups of A8, A10, A12, B8, B10, B12, C8, C10 and C12 were compared and evaluated. ResultsCompared to A8, A10 A12, C8, C10 or C12 groups, the thoracoscope instruments in the stainless steel containers in B8, B10 or B12 group had higher hydrogen peroxide concentrations and shorter elapsed time in the pressure check phases 1 and phases 2, with the differences statistically significant (P<0.05), followed by the silicone resin case group and the polyethylene case group. The nine groups of physical parameter monitoring, the first type of chemical indicator monitoring, and the five types of chemical PCD monitoring for lumen sterilization achieved 100% qualification rates, and there were no significant differences in the qualified rates of sterilization among the 9 groups (P>0.05). ConclusionWhen using hydrogen peroxide low temperature plasma to sterilize thoracoscopic instruments, it is recommended to use stainless steel or silicone resin rigid containers with a controlled loading capacity (≤12) to ensure optimal sterilization quality.

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

OBJECTIVE: This review summarized the first 10-year progresses and controversies in the concept of anteromedial cortical support reduction, to provide references for further study and clinical applications. METHODS: Relevant domestic and foreign literature on cortical support reduction was extensively reviewed to summarize the definition of positive, neutral, and negative support, anteromedial cortices at the inferior corner, intraoperative technical tips for fracture reduction, radiographic assessment at different periods, comparison between positive versus neutral and medial versus anterior support, and the clinical efficacy of Chang reduction quality criteria (CRQC) and postoperative stability score. RESULTS: Anteromedial cortical support reduction was only focused on the cortex of anteromedial inferior corner, with no concern the status of lateral wall or lesser trochanter. Anteromedial cortex was seldom involved by fracture comminution, it was thicker, denser, and stronger, and was the key for mechanical buttress of the head-neck fragment to share compression load. Positive, neutral, and negative support were also called "extramedullary, anatomic, and intramedullary reduction", respectively. There was hardly seen parallel cortical apposition, but characterized by some kinds of head-neck rotation, for example 10°-15° flexed rotation for positive cortical contact and support. Due to intraoperative compression and postoperative impaction, the status of cortical support may be changed at different time of radiographic examination. The positive medial cortex support was more reliable with less reduction loss than its neutral counterpart, and the anterior cortex contact was more predictive than the medial cortex for final results. As incorporation the bearing of cortex apposition and using a 4-point score, CRQC demonstrated more efficacy and was gradually accepted and applied in the evaluation of trochanteric fracture reduction quality. Postoperative stability score (8 points) provided a assessment tool for early weight-bearing in safety to prevent mechanical failure. CONCLUSION Anteromedial cortical support reduction is a key point for stability reconstruction in the treatment of trochanteric femur fractures. Evidence has definitely shown that non-negative (positive and neutral) is superior to negative (loss of cortical support). There is a tendency that positive cortex support is superior to neutral, but high quality study with large sample size is needed for a clear conclusion.
Humans ; Femur/diagnostic imaging* ; Fracture Fixation, Internal/methods* ; Hip Fractures/diagnostic imaging* ; Treatment Outcome ; Fracture Fixation, Intramedullary/methods*

OBJECTIVE: To analyze the gene mutation characteristics and survival time of patients with newly diagnosed acute myeloid leukemia (AML) based on next-generation sequencing(NGS) gene detection. METHODS: A retrospective analysis was conducted on the clinical data of 92 patients with AML (non APL) admitted to our hospital from January 2018 to May 2022. AML related genes tested were using NGS, the mutation characteristics and survival time of AML patients were analyzed. RESULTS: Among the 92 patients, 41 were males and 51 were females. A total of 38 types of gene mutations were detected. Six-two patients carried at least one gere mutation, while no gene mutations were detected in 30 patients. In the group with favourable prognosis (n =14), the frequencies of higher gene mutations were NRAS, KIT (21.43%, n =3), KRAS (14.29%, n =2). In the group with intermediate prognosis (n =64), the gene mutation frequencies from high to low were DNMT3A (18.75%, n =12), NPM1 (17.19%, n =11), IDH2, FLT3-ITD, CEBPA (12.50%, n =8), TET2 (10.94%, n =7). In the poor prognosis group (n =14), ASXL1, TP53, EZH2, NRAS had higher gene mutation frequency than others(14.29 %, n =2 ). Statistical analysis revealed that KIT had a relative hotspot of mutations in the intermediate-risk group, and DNMT3A had a relative hotspot of mutations in the high-risk group (P < 0.05). The correlation analysis of genes with high mutation rates in different prognostic groups, such as NRAS, KIT, IDH2, DNMT3A, NPM1, and FLT3-ITD, with prognosis found that KIT was a factor affecting OS (P < 0.05), while no significant differences were observed for the others(P >0.05). CONCLUSION The frequency of gene mutations is high in AML patients, 67.4% of the patients carried at least one gene mutation. The mutation frequency varies among different genes in patients with different karyotypes, and there are obvious dominant mutations. KIT and DNMT3A can be used as factors for evaluating the prognosis of AML.
Humans ; Leukemia, Myeloid, Acute/genetics* ; Nucleophosmin ; Mutation ; Prognosis ; Retrospective Studies ; Male ; Female ; High-Throughput Nucleotide Sequencing ; Middle Aged ; DNA Methyltransferase 3A ; Adult ; Aged ; Survival Analysis ; Proto-Oncogene Proteins c-kit/genetics*

OBJECTIVE: To assess the value of the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) score combined with PSA density (PSAD) in the diagnosis of clinically significant prostate cancer (CSPCa) in the PSA grey zone by MRI-TRUS cognitive fusion-guided transperineal targeted prostate biopsy. METHODS: This retrospective study included 327 male patients with total PSA (tPSA) levels of 4-10 μg/L undergoing MRI-TRUS cognitive fusion-guided transperineal targeted prostate biopsy in our hospital between January 2021 and December 2023. According to the pathological results, we divided the patients into a CSPCa (n = 44) and a non-CSPCa group (n = 283), collected their clinical and imaging data, and subjected them to statistical analysis. RESULTS: The age, tPSA level, PSAD and PI-RADS score were significantly higher, while the free PSA (fPSA) level, f/tPSA ratio and prostate volume remarkably lower in the CSPCa than in the non-CSPCa group (P<0.05). The areas under the curve (AUCs) of PSAD, PI-RADS score and their combination were 0.772, 0.730 and 0.801, with sensitivities of 63.63%, 70.45% and 72.73%, and specificities of 84.10%, 75.62% and 83.75%, respectively (P<0.01). With PSAD 0.2 μg/(ml·cm3) as the best cut-off value and based on the PI-RADS scores, the patients were divided into two groups for analysis. In the patients with PI-RADS scores 2 and 5, the AUCs were 0.534 and 0.643, with sensitivities of 16.67% and 63.64%, and specificities of 85.14% and 64.29%, with no statistically significant differences (P= 0.784, P= 0.228), and in those with PI-RADS scores 3 and 4, the AUCs were 0.794 and 0.843, with sensitivities of 57.14% and 80.00%, and specificities of 87.14% and 81.82%, with statistically significant differences (P= 0.009, P<0.001). CONCLUSION PI-RADS v2.1 score combined with PSAD can effectively improve the diagnostic efficiency of CSPCa in the PSA grey zone by MRI-TRUS cognitive fusion-guided transperineal targeted prostate biopsy and serve as a guide for selection of prostate biopsy.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Retrospective Studies ; Prostate-Specific Antigen ; Magnetic Resonance Imaging ; Image-Guided Biopsy ; Prostate/pathology* ; Aged ; Middle Aged