ObjectiveThrough qualitatively and quantitatively analysis of the differences in chemical composition between the combined decoction and single decoction of Huaganjian and comparison of their core efficacy， to explore the rationality of the flexible clinical application of Huaganjian compound preparations and single-flavored dispensing granules. MethodsUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to qualitatively analyze the combined decoction and single decoction samples of Huaganjian， and meanwhile， the contents of four index components（geniposide， paeoniflorin， hesperidin and paeonol） were quantitatively analyzed by high performance liquid chromatography（HPLC）. Nonalcoholic fatty liver disease（NAFLD） rat model induced by high-fat diet was applied to compare the efficacy of combined decoction and single decoction of Huaganjian. A total of 30 male SD rats were randomly divided into the control group， model group， lovastatin group（1.8 mg·kg^-1）， combined decoction group（1.26 g·kg^-1） and single decoction group（1.18 g·kg^-1）. After successful modeling， lovastatin group， combined decoction group and single decoction group were given corresponding doses of drugs by intragastric administration every day， and the control group and model group were given equal amounts of normal saline by intragastric administration， after 4 weeks of administration， the serum and liver tissues were collected， and the contents of alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， total cholesterol（TC）， triglyceride（TG）， low-density lipoprotein cholesterol（LDL-C） and high-density lipoprotein cholesterol（HDL-C） in serum of rats were detected， and the liver pathological examination was carried out by hematoxylin-eosin（HE） staining and oil red O staining， so as to compare differences of their efficacy. ResultsSeventy chemical components were initially identified and attributed from the lyophilized powder of the combined decoction and single decoction samples of Huaganjian， and there was no obvious difference in composition between the two. Further quantitative analysis showed that the contents of geniposide， paeoniflorin， hesperidin and paeonol in the combined decoction samples were significantly increased when compared with those of the single decoction samples（P<0.01）. The pharmacodynamic results showed that compared with the model group， both the combined and single decoction groups of Huaganjian could improve the liver index of NAFLD rats， reduce the serum levels of AST， ALT， TC， TG and LDL-C， increase the serum level of HDL-C， and ameliorate the pathological changes of liver cell steatosis and fat accumulation. However， there was no significant difference in pharmacodynamic effects between the combined decoction group and the single decoction group. ConclusionThere is no significant difference between the combined decoction and single decoction of Huaganjian in terms of chemical composition， but the contents of the four index components show significantly difference. Both of them can significantly improve the fat accumulation and liver function in NAFLD rats. This study provides a reference basis for the rational clinical application and evaluation of famous classical formula compound preparations and single-flavored dispensing granules.

OBJECTIVE To enhance the training quality of anticoagulation specialty clinical pharmacists， address the resource limitations of a single training base， and promote homogenization of training quality. METHODS A multi-base joint training system for anticoagulation specialty clinical pharmacists in the Beijing area was established. A mixed research method was employed， collecting data through performance comparisons， questionnaires， and qualitative interviews to compare the differences between the joint training model （experimental group， n＝16） and traditional teaching model （the control group， n＝17）. RESULTS The established joint training system encompassed a unified joint training teaching plan， the formation of a joint training teaching team， the establishment of joint theoretical teaching courses， the implementation of joint case discussions and literature presentations， as well as strengthening the assessment throughout the joint training process. Compared to the control group [theoretical assessment of （76.44±3.66） points， case assessment of （84.31±3.27） points]， the experimental group students achieved higher scores in theoretical assessment （[ 79.85±4.64） points] and case assessment （[ 88.70±5.51） points] （P＜0.05）. Through questionnaires and qualitative interviews， the trainees in experimental group were highly satisfied with the joint training model in terms of theoretical learning， communication skills， and teaching interaction. CONCLUSIONS The multi-base collaborative training system for anticoagulation specialty clinical pharmacists can integrate advantageous resources and significantly enhance the training effectiveness of anticoagulation specialty clinical pharmacists， offering value for wider promotion.

OBJECITVE: To investigate the effectiveness of three-dimensional (3D) printing-assisted vascularized fibular graft for repairing metatarsal defects. METHODS: Between November 2021 and February 2024, 11 patients with varying degrees of metatarsal defects caused by trauma were treated. There were 10 males and 1 female, aged 22-67 years, with a mean age of 51.2 years. The defect locations were as follows: the first metatarsal in 4 cases, the fifth metatarsal in 2 cases, the first and the second metatarsals in 1 case, the first to third metatarsals in 1 case, the third and the fourth metatarsals in 1 case, the third to fifth metatarsals in 1 case, and the first to fifth metatarsals in 1 case. The preoperative American Orthopaedic Foot & Ankle Society (AOFAS) score was 67.0 (48.5, 72.5). Based on 3D-printed bilateral feet models and mirrored healthy-side foot arch angles for preoperative planning and design, the vascularized fibular graft was performed to repair the metatarsal defects. At last follow-up, the medial and lateral longitudinal arches of bilateral feet were measured on weight-bearing X-ray films, and functional assessment was conducted using the AOFAS score. RESULTS: All operations were successfully completed, with an operation time ranging from 180 to 465 minutes (mean, 246.8 minutes). All incisions healed by first intention, with no occurrence of osteomyelitis. All patients were followed up 6-22 months (mean, 10 months). X-ray film reviews showed bone graft healing in all cases, with a healing time of 3-6 months (mean, 5 months). All patients underwent internal fixator removal at 6-12 months after operation. At last follow-up, no significant difference was observed in the medial and lateral longitudinal arches between the healthy and affected feet ( P>0.05). The AOFAS score of the affected foot was 78.0 (73.5, 84.0), showing a significant improvement compared to the preoperative score ( P<0.05). The effectiveness was rated as excellent in 1 case, good in 7 cases, fair in 2 cases, and poor in 1 case. Linear scarring remained at the donor site, with no functional impairment in adjacent joint movement. CONCLUSION 3D printing-assisted vascularized fibular graft for repairing metatarsal defects can effectively restore the physiological angle of the foot arch, facilitate the recovery of weight-bearing alignment, promote good bone healing, and yield satisfactory clinical outcomes.
Humans ; Printing, Three-Dimensional ; Middle Aged ; Male ; Fibula/blood supply* ; Female ; Metatarsal Bones/injuries* ; Adult ; Bone Transplantation/methods* ; Aged ; Plastic Surgery Procedures/methods* ; Young Adult ; Treatment Outcome

The clinical antiprotozoal drug nitazoxanide has been demonstrated to improve the experimental diabetes mellitus, lipid metabolism disorders, atherosclerosis and inhibit inflammation. Since the pathogenesis of heart failure with preserved ejection (HFpEF) is multifactorial and closely associated with the aforementioned diseases, we aim to study the effect of nitazoxanide on high-fat diet (HFD) plus L-NAME (N ω-nitro-l-arginine methyl ester)-induced HFpEF and metabolic syndrome in mice. We found that oral nitazoxanide improved cardiac hypertrophy, cardiac fibrosis, cardiac diastolic dysfunction, increased blood pressure, impaired exercise tolerance, impaired glucose handling, serum lipid disorders, hepatic steatosis, increased weight of white adipose tissues and kidney fibrosis in HFD + L-NAME-treated mice. In the established HFD + L-NAME-induced HFpEF and metabolic syndrome mouse model, therapeutic treatment with nitazoxanide rescued HFD + L-NAME-induced pathological phenotypes as mentioned above. The in vitro experiments revealed that tizoxanide, the active metabolite of nitazoxanide, increased the basal mitochondria metabolism of cardiomyocytes, inhibited cardiomyocyte hypertrophy and collagen secretion from cardiac fibroblasts, and relaxed phenylephrine- and U46619-induced constriction of rat mesenteric arteries, indicating that the direct effect of tizoxanide might partly contribute to the protective effect of nitazoxanide against HFpEF in vivo. The present study suggests that nitazoxanide might be a potential drug for HFpEF and metabolic syndrome therapy.

OBJECTIVES: To explore the therapeutic mechanism of compound Centella asiatica formula (CCA) for alleviating Schistosoma japonicum (Sj)-induced liver fibrosis in mice. METHODS: The active components and targets of CCA were identified using the TCMSP database with cross-analysis of Sj-related liver fibrosis targets. A "drug-component-target-pathway-disease" network was constructed using Cytoscape 3.9.1. Functional enrichment analysis (GO/KEGG) was performed using DAVID. Molecular docking study was carried out to validate interactions between the core targets and the key compounds. For experimental validation of the results, 36 mice were divided into control group, Sj-infected model group, and CCA-treated groups. In the latter two groups, liver fibrosis was induced via abdominal infection with Sj cercariae for 8 weeks, followed by 8 weeks of daily treatment with CCA decoction or saline. Hepatic pathology of the mice was assessedwith HE and Masson staining, and hepatic expressions of collagen-I and collagen-III were detected using immunohistochemistry; serum IL-6 and TNF-α levels were determined with ELISA. Hepatic expressions of TLR4 and MyD88 proteins were analyzed with Western blotting. RESULTS: We identified a total of 107 bioactive CCA components and 791 targets, including 37 intersection targets linked to Sj-induced fibrosis. The core targets included TNF, TP53, JUN, MMP9, and CXCL8, involving the IL-17 signaling, lipid metabolism, TLR4/MyD88 axis, and cancer pathways. Molecular docking study confirmed strong binding affinity between quercetin (a primary CCA component) and TNF/TP53/JUN/MMP9. In Sj-infected mouse models, CCA treatment significantly attenuated hepatic inflammatory cell infiltration, reduced collagen-I and collagen-III deposition, improved tissue architecture, reduced serum IL-6 and TNF-α levels, and downregulated TLR4 and MyD88 expressions in the liver. CONCLUSIONS CCA mitigates Sj-induced liver fibrosis by targeting TNF, TP53, JUN, and MMP9 to modulate the TLR4/MyD88 pathway, thereby suppressing pro-inflammatory cytokine release, inhibiting hepatic stellate cell activation, reducing collagen deposition, and preventing granuloma formation in the liver.
Animals ; Toll-Like Receptor 4/metabolism* ; Mice ; Myeloid Differentiation Factor 88/metabolism* ; Schistosoma japonicum ; Liver Cirrhosis/parasitology* ; Schistosomiasis japonica ; Signal Transduction ; Molecular Docking Simulation ; Inflammation ; Centella/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*

Objective To analyze the differences and connections between the current grading and classification methods for nuclear medicine workplaces, and to provide technical guidance for environmental impact assessments and technical reviews. Methods By comparing the objects, purposes, and computational approaches between the two methods, this article illustrates the usage of both methods through specific examples and analyzes the relationship between them. Results The two methods differed in objects, purposes, and computational approaches. The A, B, and C grading scheme was primarily used to establish the level of administrative supervision for an entire nuclear medicine workplace. In contrast, the I, II, and III classification system specifies the hardware facilities and engineering protection requirements of internal places or rooms. Conclusion These two methods are complementary and collectively provide a complete framework for the assessment of nuclear medicine workplaces.

Objective:To investigate the diagnostic value of plasma cytokines such as interleukin (IL)-2, IL-6 and interferon (IFN)-γ in non-Hodgkin lymphoma (NHL).Methods:A retrospective case-control study was conducted. A total of 48 NHL patients admitted to the Second Affiliated Hospital of Xuzhou Medical University between January 2020 and December 2022 were selected as NHL group, and another 34 healthy people who underwent physical examimation during the same period were selected as the healthy control group. The levels of IL-2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor (TNF) - α and IFN-γ in the plasma of patients at first admission and healthy subjects during physical examination were detected by using flow cytometry. The differences in general data and all cytokines levels of both groups were compared. The collinearity stepwise screening was made in 7 cytokines levels, and the screened variables were included in multivariate binary logistic regression model. Plasma cytokines with independent effects on the pathogenesis of NHL were screened. Taking local biopsy, histopathological examination or immunohistochemical examination as the gold standard, the receiver operating characteristic (ROC) curves of individual and combined diagnosis of NHL based on the selected cytokines were drawn to judge the diagnostic effect of all indicators on NHL.Results:There were 32 males (66.7%) and 16 females (33.3%) in NHL group, with the median age [ M ( Q1, Q3)] of 56.50 (45.75, 67.50) years; there were 28 males (82.4%) and 6 females (17.6%) in the healthy control group, with the median age of 52.00 (47.50, 55.50) years. There were no statistically significant differences in age and gender composition between the 2 groups (all P > 0.05). The levels of IL-2 [1.44 (1.36, 1.85) pg/ml vs. 1.19 (0.86, 1.68) pg/ml] and TNF-α [3.46 (2.68, 4.06) pg/ml vs. 2.23 (1.52, 3.46) pg/ml] in NHL group were higher than those in the healthy control group, and the differences were statistically significant (all P < 0.05). There were no statistically significant differences in IL-4, IL-6, IL-10, IL-17, IFN-γ levels (all P > 0.05). According to collinear stepwise screening of independent variables, IL-4 and TNF-α were excluded from 7 cytokines, and the other 5 cytokines were included in multivariate logistic regression model, and the result showed that the decreased level of IL-2 ( OR = 0.20, 95% CI: 0.08-0.53, P = 0.001) and the increased levels of IL-6 ( OR = 1.18, 95% CI: 1.04-1.33, P = 0.009) and IFN-γ ( OR = 1.26, 95% CI: 1.08-1.46, P = 0.003) were independent risk factors for the onset of NHL. The results showed that the area under the curve of IL-2, IL-6, IFN-γ and the combination of 3 indexes for the diagnosis of NHL was 0.760 (95% CI: 0.651-0.870), 0.595 (95% CI: 0.468-0.722), 0.508 (95% CI: 0.373-0.642), 0.847 (95% CI: 0.763-0.930), and the optimal cut-off value of the combination of 3 indexes was 0.730 which was calculated by logistic regression model formula; the corresponding sensitivity and specificity were 70.2% and 94.1%, respectively. Conclusions:The decreased level of IL-2 and increased levels of IL-6 and IFN-γ at initial diagnosis are risk factors for the onset of NHL. The combined detection of the 3 indexes shows a good value in the diagnosis of NHL.

Objective : To investigate the mechanism of action of benvitimod (BVM) in the treatment of atopic der- matitis (AD) . Methods : HaCaT cells were stimulated by TNF-α and IFN-γ , and the cells were grouped into NC group , TNF-α/IFN-γ group , TNF-α/IFN-γ BVM group , and TNF-α/IFN-γ BVM ML385 group. The AD model of DNCB-induced Balb/c mice was divided into CON group , DNCB group , DNCB + BVM group , and DNCB + TAC group. The efficacy of BVM and its roles in antioxidant and pyroptosis regulation were evaluated. Results: Compared with the control group , BVM inhibited the inflammatory response of HaCaT cells stimulated by TNF-α and IFN-γ , and ameliorated the skin lesions and inflammation in the DNCB-induced AD mouse model ; at the same time , it significantly increased the expression of nuclearfactorerythroid-2-relatedfactor2 (NRF2)-related anti-oxida- tive stress proteins , and significantly reduced the expression of cellular reactive oxygen species (ROS) levels and pyroptosis proteins. At the same time , the levels of NRF2-related antioxidative stress proteins significantly in- creased , and the levels of ROS and pyroptosis proteins significantly decreased. Conclusion BVM activates the NRF2/ROS/NLRP3 pathway to inhibit pyroptosis , thereby reducing the inflammatory response in AD.

Objective:Osteosarcoma is a highly aggressive primary malignant bone tumor commonly seen in children and adolescents,with a poor prognosis.Anchorage-dependent cell death(anoikis)has been proven to be indispensable in tumor metastasis,regulating the migration and adhesion of tumor cells at the primary site.However,as a type of programmed cell death,anoikis is rarely studied in osteosarcoma,especially in the tumor immune microenvironment.This study aims to clarify prognostic value of anoikis and tumor immune microenvironment-related gene in the treatment of osteosarcoma. Methods:Anoikis-related genes(ANRGs)were obtained from GeneCards.Clinical information and ANRGs expression profiles of osteosarcoma patients were sourced from the therapeutically applicable research to generate effective therapies and Gene Expression Omnibus(GEO)databases.ANRGs highly associated with tumor immune microenvironment were identified by the estimate package and the weighted gene coexpression network analysis(WGCNA)algorithm.Machine learning algorithms were performed to construct long-term survival predictive strategy,each sample was divided into high-risk and low-risk subgroups,which was further verified in the GEO cohort.Finally,based on single-cell RNA-seq from the GEO database,analysis was done on the function of signature genes in the osteosarcoma tumor microenvironment. Results:A total of 51 hub ANRGs closely associated with the tumor microenvironment were identified,from which 3 genes(MERTK,BNIP3,S100A8)were selected to construct the prognostic model.Significant differences in immune cell activation and immune-related signaling pathways were observed between the high-risk and low-risk groups based on tumor microenvironment analysis(all P<0.05).Additionally,characteristic genes within the osteosarcoma microenvironment were identified in regulation of intercellular crosstalk through the GAS6-MERTK signaling pathway. Conclusion:The prognostic model based on ANRGs and tumor microenvironment demonstrate good predictive power and provide more personalized treatment options for patients with osteosarcoma.