OBJECTIVE To form an expert consensus addressing clinical issues regarding the use of parenteral direct thrombin inhibitors （DTIs） in special populations. METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital（the Affiliated Hospital of UESTC）， a multidisciplinary working group was formed comprising experts from multiple fields， including clinical pharmacy， cardiac surgery， obstetrics， pediatrics and evidence-based medicine. Through literature review and the Delphi method， clinical questions regarding the efficacy and safety of parenteral DTIs used in special populations were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” （PICO） framework；systematic searches were conducted in CJFD， PubMed， Embase and other databases. Relevant evidence from randomized controlled trials，cohort studies and systematic reviews were included and synthesized. Evidence quality was assessed using the Grading of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through three rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven clinical questions were ultimately selected （with a consensus rate exceeding 90%）， resulting in the formulation of seven recommendations on the use of parenteral DTIs in special populations， including children， pregnant women， patients with hepatic or renal impairment， patients with mesenteric venous thrombosis， and individuals with thrombophilia. These recommendations clarify the preferred agents， dosing ranges， monitoring parameters， and safety management strategies for parenteral DTIs in these special populations. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in special populations.

With the aging of the global population， osteoporosis （OP） is becoming a major public health concern worldwide. Currently， the commonly used anti-osteoporosis drugs in clinical practice have limited application due to many side effects. Therefore， developing more effective and safer strategies for the prevention and treatment of OP has become a research focus in this field. In recent years， the clinical efficacy and advantages of traditional Chinese medicine （TCM） in treating OP have been gradually recognized. With the deepening pharmacological research on TCM for OP prevention and treatment， it is found that the active ingredients of Scutellaria baicalensis can promote bone formation or inhibit bone resorption by regulating signaling pathways， including Wnt/β-catenin， osteoprotegerin （OB）/receptor activator of nuclear factor-κB ligand （RANKL）/RANK （OPG/RANKL/RANK）， and bone morphogenetic protein 2 （BMP-2）/Smad， mitogen-activated protein kinase （MAPK）， and mammalian target of rapamycin （mTOR）. However， existing research on active ingredients of S. baicalensis for OP treatment is scattered， making it difficult for scholars to gain a systematic understanding of its research and application. This review summarized the literature on the active ingredients of S. baicalensis in OP treatment worldwide， clarified their mechanisms of action， and explored some issues， providing references for the integration of TCM in OP prevention and treatment.

With the aging of the global population， osteoporosis （OP） is becoming a major public health concern worldwide. Currently， the commonly used anti-osteoporosis drugs in clinical practice have limited application due to many side effects. Therefore， developing more effective and safer strategies for the prevention and treatment of OP has become a research focus in this field. In recent years， the clinical efficacy and advantages of traditional Chinese medicine （TCM） in treating OP have been gradually recognized. With the deepening pharmacological research on TCM for OP prevention and treatment， it is found that the active ingredients of Scutellaria baicalensis can promote bone formation or inhibit bone resorption by regulating signaling pathways， including Wnt/β-catenin， osteoprotegerin （OB）/receptor activator of nuclear factor-κB ligand （RANKL）/RANK （OPG/RANKL/RANK）， and bone morphogenetic protein 2 （BMP-2）/Smad， mitogen-activated protein kinase （MAPK）， and mammalian target of rapamycin （mTOR）. However， existing research on active ingredients of S. baicalensis for OP treatment is scattered， making it difficult for scholars to gain a systematic understanding of its research and application. This review summarized the literature on the active ingredients of S. baicalensis in OP treatment worldwide， clarified their mechanisms of action， and explored some issues， providing references for the integration of TCM in OP prevention and treatment.

Objective To explore the independent risk factors for long-term adverse prognosis after percutaneous renal artery angioplasty in patients with transplant renal artery stenosis(TRAS).Methods We retrospectively collected medical records and surgery details of TRAS patients who underwent renal artery angioplasty at the Department of Peripheral Vascular Diseases,The First Affiliated Hospital of Xi'an Jiaotong University,from January 2017 to June 2021.All patients were followed up for 3 years post-operation.Multivariate Cox regression analyses were performed to find the independent predictive factors for long-term adverse prognosis after renal artery angioplasty in the TRAS patients.Results A total of 45 TRAS patients who underwent percutaneous renal artery angioplasty were included in this study.During the five-year follow-up period,10 patients(22.2％)experienced long-term adverse events.These consisted of 3 patients(6.7％)who died from any cause,1 patient(2.2％)who developed transplant renal artery dissection,6 patients(13.3％)who had restenosis of the transplant renal artery,and 1 patient(2.2％)who lost the transplant kidney and received dialysis again.Multivariate Cox regression analysis showed that male gender(HR=4.915,95％CI:1.036-23.328,P=0.045)and balloon angioplasty alone(HR=8.594,95％CI:2.191-33.710,P=0.002)were independent risk factors for long-term adverse prognosis after renal artery angioplasty in TRAS patients.Conclusion Male gender and balloon angioplasty alone are independent risk factors for long-term adverse prognosis after renal artery angioplasty in TRAS patients.

Objective:To investigate the curative effect and possible mechanism of rifaximin treatment on monocrotaline-induced hepatic sinusoidal obstruction syndrome (HSOS) in mice.Methods:Twenty-four male C57BL/6J mice were divided into three groups and treated with solvent control, monocrotaline, and rifaximin, respectively. The histopathological changes of the liver and intestine were observed by hematoxylin-eosin staining. The differences were compared in liver parameters, serum liver enzymes, inflammatory factors, apoptotic factors, gut microbiota, and gut tight junction proteins among three groups of mice. The inter-group comparison was conducted using a t-test and one-way analysis of variance.Results:The rifaximin-treated group had significantly improved liver histopathology. The serological levels of alanine aminotransferase and aspartate aminotransferase were (559.04±89.42) U/L and (676.90±106.25) U/L, respectively, which were significantly lower than those in the PA-HSOS model group [(846.05±148.46) U/L and (953.87±58.10) U/L, P<0.05], and were accompanied by lower levels of apoptotic cells and inflammatory factors. Additionally, the rifaximin-treated mice group gut microbiota had higher diversity compared with the PA-HSOS group ( P<0.05), and the Shannon index was 7.77±0.10 and 7.16±0.07, respectively, indicating apparent differences in microbiota among different groups. The abundance of Firmicutes in the rifaximin group was 39.58%±0.56%, which was significantly higher than that in the model group (24.25%±0.64%, P<0.05), while the abundance of Bacteroidetes was 54.7%±0.41%, which was significantly lower than that in the model group (70.92%±0.49%, P<0.05). Simultaneously, the expressions of gut tight junction proteins ZO-1 and Occludin showed an upward trend and validated transcription levels compared to the model group following rifaximin intervention ( P<0.05). Conclusion:Rifaximin can alleviate monocrotaline-induced hepatic sinusoidal obstruction syndrome in mice, and its mechanism may be via gut microbiota regulation, which in turn plays a role in improving intestinal barrier function.

ObjectiveTo develop a nomogram-based risk prediction model for chronic obstructive pulmonary disease (COPD) incidence among the community-dwelling population aged 40 years old and above, so as to provide targeted references for the screening and prevention of COPD. MethodsBased on a natural population cohort in suburban Shanghai, a total of 3 381 randomly selected participants aged ≥40 years underwent pulmonary function tests between July and October 2021. Cox stepwise regression analysis was used to develop overall and gender-specific risk prediction models, along with the construction of corresponding risk nomograms. Model predictive performance was evaluated using the C-indice, area under the curve (AUC) values, and Brier score. Stability was assessed through 10-fold cross-validation and sensitivity analysis. ResultsA total of 3 019 participants were included, with a median follow-up duration of 4.6 years. The COPD incidence density was 17.22 per 1 000 person-years, significantly higher in males (32.04/1 000 person-years) than that in females (7.38/1 000 person-years) (P<0.001). The overall risk prediction model included the variables such as gender, age, education level, BMI, smoking, passive smoking, and respiratory comorbidities. The male-specific model incorporated the variables such as age, BMI, respiratory comorbidities, and smoking, while the female-specific model included age, marital status, respiratory comorbidities, and pulmonary tuberculosis history. The C-indices for the overall, male-specific, and female-specific models were 0.829, 0.749, and 0.807, respectively. The 5-year AUC values were 0.785, 0.658, and 0.811, with Brier scores of 0.103, 0.176, and 0.059, respectively. Both 10-fold cross-validated C-indices and sensitivity analysis (excluding participants with a follow-up duration of <6 months) yielded C-indices were above 0.740. ConclusionThis study developed concise and practical overall and gender-specific COPD risk prediction models and corresponding nomograms. The models demonstrated robust performance in predicting COPD incidence, providing a valuable reference for identifying high-risk populations and formulating targeted screening and personalized management strategies.

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 establish a three-dimensional finite element model of a digital wire loop space maintainer for the mandible and primary tooth loss, in order to investigate the stress, deformation, and shear force experienced by patients with the loss of the second primary molar when wearing the wire loop space maintainer. METHODS: Cone beam computed tomography (CBCT) scans were performed on the patients to create a digital model of the mandible with the absence of the second primary molar using Mimics 21.0 software. A digital model integrating the crown's retention and the wire loop structure of the full crown and ring wire loop space maintainer was constructed using pediatric space maintainer design software, utilizing three different materials: cobalt-chromium alloy, polyether ether ketone (PEEK), and titanium alloy. In ANSYS Work Beach 2023 R2 software, vertical loads of 70 N, tilted 45° along the long axis of the tooth loads of 70 N, and a 10 N load on the surface of the wire loop were applied to the occlusal surfaces of models 46 and 84, simulating centric and lateral occlusions during chewing with the wire loop space maintainer in place. The stress states of the wire loop space maintainer and supporting teeth were analyzed. RESULTS: Under various loading conditions, the maximum principal stress of the ring wire loop space maintainer was significantly lower than that of the full crown. Stress contour maps indicated that the peak of the maximum principal stress occurred at the junction of the wire loop and crown structure, indicating that this area was more susceptible to fracture. The ring wire loop space maintainer made from PEEK material exhibited the lowest maximum shear stress on the internal organizational surfaces, with equivalent stresses of 23.18 MPa and 36.35 MPa for models 46 and 84, respectively. Stress contour maps demonstrated that the maximum stress on tooth 46 was located at its mesial, while the maximum stress on tooth 84 was situated near the root area on its distal, in contact with the wire loop space maintainer. CONCLUSION In cases of second primary molar loss, wearing the digital ring wire loop space maintainer can effectively distribute stress, and the ring wire loop space maintainer made from PEEK material reduces the stress experienced by supporting teeth to some extent, demonstrating its superiority in clinical application.
Finite Element Analysis ; Humans ; Tooth, Deciduous ; Cone-Beam Computed Tomography ; Space Maintenance, Orthodontic/methods* ; Imaging, Three-Dimensional ; Orthodontic Wires ; Dental Stress Analysis ; Mandible ; Stress, Mechanical

OBJECTIVE: To investigate the anti-inflammatory effect of rutaecarpine (RUT) on monosodium urate crystal (MSU)-induced murine peritonitis in mice and further explored the underlying mechanism of RUT in lipopolysaccharide (LPS)/MSU-induced gout model in vitro. METHODS: In MSU-induced mice, 36 male C57BL/6 mice were randomly divided into 6 groups of 8 mice each group, including the control group, model group, RUT low-, medium-, and high-doses groups, and prednisone acetate group. The mice in each group were orally administered the corresponding drugs or vehicle once a day for 7 consecutive days. The gout inflammation model was established by intraperitoneal injection of MSU to evaluate the anti-gout inflammatory effects of RUT. Then the proinflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and the proportions of infiltrating neutrophils cytokines were detected by flow cytometry. In LPS/MSU-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and proinflammatory cytokines were measured by ELISA. The percentage of pyroptotic cells were detected by flow cytometry. Respectively, the mRNA and protein levels were measured by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot, the nuclear translocation of nuclear factor κB (NF-κB) p65 was observed by laser confocal imaging. Additionally, surface plasmon resonance (SPR) and molecular docking were applied to validate the binding ability of RUT components to tumor necrosis factor α (TNF-α) targets. RESULTS: RUT reduced the levels of infiltrating neutrophils and monocytes and decreased the levels of the proinflammatory cytokines interleukin 1β (IL-1β) and interleukin 6 (IL-6, all P<0.01). In vitro, RUT reduced the production of IL-1β, IL-6 and TNF-α. In addition, RT-PCR revealed the inhibitory effects of RUT on the mRNA levels of IL-1β, IL-6, cyclooxygenase-2 and TNF-α (P<0.05 or P<0.01). Mechanistically, RUT markedly reduced protein expressions of tumor necrosis factor receptor (TNFR), phospho-mitogen-activated protein kinase (p-MAPK), phospho-extracellular signal-regulated kinase, phospho-c-Jun N-terminal kinase, phospho-NF-κB, phospho-kinase α/β, NOD-like receptor thermal protein domain associated protein 3 (NLRPS), cleaved-cysteinyl aspartate specific proteinase-1 and cleaved-gasdermin D in macrophages (P<0.05 or P<0.01). Molecularly, SPR revealed that RUT bound to TNF-α with a calculated equilibrium dissociation constant of 31.7 µmol/L. Molecular docking further confirmed that RUT could interact directly with the TNF-α protein via hydrogen bonding, van der Waals interactions, and carbon-hydrogen bonding. CONCLUSION RUT alleviated MSU-induced peritonitis and inhibited the TNFR1-MAPK/NF-κB and NLRP3 inflammasome signaling pathway to attenuate gouty inflammation induced by LPS/MSU in THP-1 macrophages, suggesting that RUT could be a potential therapeutic candidate for gout.
Animals ; NF-kappa B/metabolism* ; Male ; Indole Alkaloids/therapeutic use* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Inflammation/complications* ; Uric Acid ; Quinazolines/therapeutic use* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Gout/chemically induced* ; Inflammasomes/metabolism* ; Cytokines/metabolism* ; THP-1 Cells ; Mitogen-Activated Protein Kinases/metabolism* ; Mice ; Molecular Docking Simulation ; Lipopolysaccharides ; Quinazolinones

Objective To explore the independent risk factors for long-term adverse prognosis after percutaneous renal artery angioplasty in patients with transplant renal artery stenosis(TRAS).Methods We retrospectively collected medical records and surgery details of TRAS patients who underwent renal artery angioplasty at the Department of Peripheral Vascular Diseases,The First Affiliated Hospital of Xi'an Jiaotong University,from January 2017 to June 2021.All patients were followed up for 3 years post-operation.Multivariate Cox regression analyses were performed to find the independent predictive factors for long-term adverse prognosis after renal artery angioplasty in the TRAS patients.Results A total of 45 TRAS patients who underwent percutaneous renal artery angioplasty were included in this study.During the five-year follow-up period,10 patients(22.2％)experienced long-term adverse events.These consisted of 3 patients(6.7％)who died from any cause,1 patient(2.2％)who developed transplant renal artery dissection,6 patients(13.3％)who had restenosis of the transplant renal artery,and 1 patient(2.2％)who lost the transplant kidney and received dialysis again.Multivariate Cox regression analysis showed that male gender(HR=4.915,95％CI:1.036-23.328,P=0.045)and balloon angioplasty alone(HR=8.594,95％CI:2.191-33.710,P=0.002)were independent risk factors for long-term adverse prognosis after renal artery angioplasty in TRAS patients.Conclusion Male gender and balloon angioplasty alone are independent risk factors for long-term adverse prognosis after renal artery angioplasty in TRAS patients.