BACKGROUND:Studies have reported that alendronate intake significantly increases bone mineral density in patients with osteoporosis. OBJECTIVE:To analyze and compare the changes in metabolites before and after alendronate intervention in ovariectomized rats by chromatography-mass spectrometry,and to further explore the specific mechanism and target of alendronate in the treatment of osteoporosis. METHODS:A total of 36 female Sprague-Dawley rats were randomly divided into model group,alendronate sodium group and sham operation group.The osteoporosis model was established by ovariectomy in the first two groups.Four weeks after modeling,the rats in the alendronate group were intragastrically given alendronate sodium,while those in the sham operation group and model group were given equal volume of normal saline.After 12 weeks of continuous gavage,the metabolites of the lumbar spine were analyzed by chromatography-mass spectrometry,and the common differential metabolites were obtained,which were analyzed by bioinformatics such as Kyoto Gene and Genome Encyclopedia pathway. RESULTS AND CONCLUSION:Totally 17 different metabolites were obtained in the three groups.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes showed that alendronate sodium could regulate unsaturated fatty acid biosynthesis,linoleic acid metabolism and other pathways to protect ovariectomized rats.These results indicate that alendronate sodium may exert its anti-osteoporosis effect by interfering with unsaturated fatty acid bioanabolism and linoleic acid metabolism,so as to achieve the purpose of preventing osteoporosis

Objective To investigate the protective effect and mechanisms of total alkaloids of Bulbus Fritillaria Pallidiflora (TA-BFP) on pulmonary fibrosis in silicosis mice. Methods i) Bulbus Fritillaria Pallidiflora (BFP) powder was collected by heating and refluxing twice with 70.00% ethanol, and the dried concentrated sample was purified using cation-exchange and macroporous adsorbent resins to obtain TA-BFP. The total alkaloids level was detected using ultraviolet spectrophotometry and the characteristic peaks in TA-BFP were identified using the high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD). ii) Specific pathogen-free male C57BL/6J mice were randomly divided into the control group, model group and intervention group, with 15 mice in each group. Mice in the model group and the intervention group were treated with 80 μL silica suspension with a mass concentration of 62.5 g/L, while the control group was treated with an equal volume of 0.9% sodium chloride solution using non-exposed tracheal instillation method. On the 28th day after modeling, mice in the intervention group were given TA-BFP at a dose of 60 mg/kg body mass, and the model group and control group were given 2.00% Tween-80 solution at the same volume by gastric gavage, once per day, for 28 days. The mouse lung tissue pathology was observed, lung organ coefficient was calculated, and inflammation and fibrosis scores were assessed after the intervention period. Serum levels of mouse interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay. Results i) The total alkaloid level of TA-BFP in the BFP powder was 50.36% after elution and purification. A total of nine alkaloid components in TA-BFP were identified by HPLC-ELSD. ii) The results of lung histopathology showed that no obvious changes of inflammation and fibrosis were identified in the lungs of mice in the control group, obvious changes of inflammation and fibrosis were identified in the lungs of mice in the model group, and the intervention group showed reduced inflammation and fibrosis in the lungs of mice compared with that of the model group. The lung organ coefficient, pulmonary inflammation score, pulmonary fibrosis score, and levels of serum IL-1β, IL-6, and TNF-α were significantly higher in the model group than those in the control group (all P<0.05). The lung organ coefficient, pulmonary inflammation score, pulmonary fibrosis score, and levels of serum IL-1β, and TNF-α were significantly higher in the intervention group than those in the control group (all P<0.05), while the pulmonary inflammation score, pulmonary fibrosis score, and levels of serum IL-1β, IL-6, and TNF-α were significantly lower in the intervention group than those in the model group (all P<0.05). Conclusion TA-BFP alleviates pulmonary inflammation in silicosis mice, thereby delaying the progression of pulmonary fibrosis. The mechanism may involve in inhibiting the expression of inflammatory factors IL-1β, IL-6, and TNF-α.

Objective To analyze the proportion and clinicopathological characteristics of HER2-positive breast cancer patients with BRCA1/2 pathogenic variants, and their response to neoadjuvant anti-HER2 targeted therapy. Methods The clinicopathological data of 531 breast cancer patients with germline BRCA1/2 pathogenic variants (201 with BRCA1 variants and 330 with BRCA2 variants) were analyzed. Results Among the 201 BRCA1 and 330 BRCA2 variants, 17 (8.5%) and 42 (12.7%) HER2-positive breast cancer cases were identified, respectively, accounting for 11.1% of all BRCA1/2-mutated breast cancers. Compared with BRCA1/2-mutated HR-positive/HER2-negative patients, HER2-positive patients did not present any significant differences in clinicopathological features; however, compared with triple-negative breast cancer patients, HER2-positive patients had a later onset age and lower tumor grade. Among the 17 patients who received neoadjuvant anti-HER2 targeted therapy, 10 cases achieved pCR (58.8%), whereas 7 cases did not (41.2%). Conclusion HER2-positive breast cancer accounts for more than 10% of BRCA1/2-mutated patients. Approximately 40% of these patients fail to achieve pCR after neoadjuvant targeted therapy. This phenomenon highlights the possibility of combining anti-HER2 targeted agents with poly (adenosine diphosphate-ribose) polymerase inhibitors.

Saponins associated with Panax notoginseng (P. notoginseng) demonstrate significant therapeutic efficacy across multiple diseases. However, certain high-yield saponins face limited clinical applications due to their reduced pharmacological efficacy. This study synthesized and evaluated 36 saponin-1,2,3-triazole derivatives of ginsenosides Rg1/Rb1 and notoginsenoside R1 for anti-adipogenesis activity in vitro. The research revealed that the ginsenosides Rg1-1,2,3-triazole derivative a17 demonstrates superior adipogenesis inhibitory effects. Structure-activity relationships (SARs) analysis indicates that incorporating an amidyl-substituted 1,2,3-triazole into the saponin side chain via Click reaction enhances anti-adipogenesis activity. Additionally, several other derivatives exhibit general adipogenesis inhibition. Compound a17 demonstrated enhanced potency compared to the parent ginsenoside Rg1. Mechanistic investigations revealed that a17 exhibits dose-dependent inhibition of adipogenesis in vitro, accompanied by decreased expression of preadipocytes. Peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4) adipogenesis regulators. These findings establish the ginsenoside Rg1-1,2,3-triazole derivative a17 as a promising adipocyte differentiation inhibitor and potential therapeutic agent for obesity and associated metabolic disorders. This research provides a foundation for developing effective therapeutic approaches for various metabolic syndromes.
Adipogenesis/drug effects* ; Triazoles/chemical synthesis* ; Ginsenosides/chemical synthesis* ; Saponins/chemical synthesis* ; Animals ; Mice ; Structure-Activity Relationship ; PPAR gamma/genetics* ; 3T3-L1 Cells ; Adipocytes/metabolism* ; Panax notoginseng/chemistry* ; Drug Design ; Molecular Structure ; Humans ; Cell Differentiation/drug effects* ; Fatty Acid-Binding Proteins/genetics*

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Tumor cells use glycolysis to provide material and energy under hypoxic conditions to meet the energy requirements for rapid growth and proliferation， namely the Warburg effect. Even under aerobic conditions， tumor cells mainly rely on glycolysis to provide energy. Therefore， glucose transporter protein 1（GLUT1）， which is involved in the process of glucose metabolism， plays an important role in tumorigenesis， development and drug resistance， and is considered to be one of the important targets in the treatment of malignant tumors. In recent years， research on tumor glucose metabolism has gradually become a hot spot. It has been shown that various factors are involved in the regulation of tumor energy metabolism， among which the role of GLUT1 is the most critical. In this paper， the authors reviewed the latest research progress of GLUT1-targeted traditional Chinese medicine（TCM） active ingredient nano-delivery system in tumor therapy， aiming to reveal the feasibility and effectiveness of this system in the delivery of chemotherapeutic drugs. The GLUT1-targeted TCM active ingredient nano-delivery system can overcome the bottleneck of the traditional targeting strategy as well as the high-permeability long retention（EPR） effect. In summary， the authors believe that the GLUT1-targeted TCM active ingredient nano-delivery system provides a new strategy for targeted treatment of tumors and has a broad application prospect in tumor prevention and treatment.

BACKGROUND:The use of blood flow restriction training in clinical rehabilitation is becoming more common,in part due to technological advances and increased interest in research and medicine. OBJECTIVE:To explore the global trend and development prospects of clinical rehabilitation-related blood flow restriction training application,identify research gaps,and propose future research directions. METHODS:Web of Science,PubMed,and Elsevier were searched for literature related to clinical rehabilitation using blood flow restriction training published from 2001 to 2022.A total of 515 articles were included for further review.Bibliometrics,exploratory factor analysis and cluster analysis were used to reveal the emerging research fields and topics. RESULTS AND CONCLUSION:First of all,the overall research trend of the number of published articles shows a steady rise.The United States is the main research area in this field,and universities contribute the most to journals.Secondly,a core group of authors,led by Loenneke JP,Abe T and Dankel SJ,has been formed,with less collaboration among highly productive authors.Finally,research on blood flow restriction training focuses on skeletal muscle rehabilitation,cognitive functional activity,and chronic disease rehabilitation in clinical rehabilitation,with particular attention to the application of blood flow restriction in the recovery of symptoms such as muscle atrophy,knee pain,and joint effusion after anterior cruciate reconstruction surgery.Theoretical research on low-pressure blood flow restriction that is effective in relieving musculoskeletal symptoms has been hot in recent years,which can systematically guide the musculoskeletal rehabilitation in clinical practice.In the future,clinicians will extend follow-up periods,register larger and more diverse sample sizes,and use randomization techniques to determine appropriate prescribing indications for rehabilitating patients,ensure clinical safety,and quantitatively analyze and develop rehabilitation protocols with the maximum effect at the minimum effective dose for different clinical populations.

BACKGROUND:The mechanisms and targets of alendronate in the treatment of osteoporosis still need to be investigated in depth. OBJECTIVE:To investigate the mechanism by which alendronate regulates bone metabolism in rats with osteoporosis and to perform a bioinformatics analysis of differentially expressed proteins. METHODS:Female Sprague-Dawley rats were randomly divided into three groups(n=12 per group):model group,alendronate group and sham-operated group.Animal models of osteoporosis were prepared using ovariectomy in the model and alendronate groups.At 4 weeks after modeling,rats in the alendronate group were gavaged with alendronate;the other two groups were given the equal volume of normal saline.After 12 weeks of continuous gavage,the bone mineral density of the tibia was measured and the lumbar spine of the rats was taken for proteomic analysis using Tandem mass tag-liquid chromatography-tandem mass spectrometry technique to identify differentially expressed proteins for gene ontology,Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction analysis. RESULTS AND CONCLUSION:There were 32 up-regulated proteins and 51 down-regulated proteins identified between the alendronate group and model group.Gene ontology enrichment analysis showed that the differentially expressed proteins were mainly involved in molecular functions,such as binding and catalytic activity,and in biological processes,such as cellular process and metabolic process.Kyoto Encylopedia of Genes and Genomes enrichment analysis showed that the differentially expressed proteins in the alendronate group and model group were mainly involved in the biosynthesis of pantothenate and coenzyme A.Protein-protein interaction analysis indicated that among the differentially expressed proteins in the alendronate group and model group,Hspa1l,Enpp3,Unc45a,Myh9 and Cant1 were located at the nodes of the protein-protein interaction network and were closely related to bone metabolism.Overall,these findings indicate that alendronate may regulate bone metabolism in the rat model of osteoporosis by regulating the expression of differentially expressed proteins and biosynthesis of pantothenate and coenzyme A.

Objective To examine the impact and partial mechanism of bupivacaine sustained-release drug(code PB21)in combination with low-dose dexamethasone(Dex)on the analgesic time of rats with knee osteoarthritis(KOA).Methods Using the techniques of anterior cruciate ligament transection and meniscus instability,a rat KOA model was created.After eight weeks,SD mice were split into three groups at random:a group for the model,one for Dex(50 μg),one for PB21(1.5 mg),and one for combined administration(1.5 mg PB21/50 μg Dex),with a control group that received a sham operation.The pain thresholds of KOA rats were measured using a Pres-sure Application Measurement(PAM)at different intervals before to delivery and 4,24,36,and 48 hours following administration;to gauge changes in discomfort,a CatWalk was used to assess the rats'average foot strength and maximum contact area before,four,twenty-four,and forty-eight hours after treatment.A portion of the rats were put to sleep at four,twenty-four,and forty-eight hours following the injection,and the joint synovium was removed for paraffin sectioning.Immunohistochemistry was used to identify the expression of GAP43 in the synovium,whereas immunofluorescence was used to identify the expression of CGRP in the same tissue.Results The average strength and maximum contact area of the foot and claw decreased(P＜0.01),and the pain threshold decreased(P＜0.01)in the model group compared to the sham operation group.The PB21+Dex group experienced a delayed pain threshold lowering time delay when compared to the PB21 and Dex treatment groups alone.Up to 48 hours lat-er,the combination administration group's average strength and maximum contact area of the foot paw remained ele-vated,and there was a statistically significant difference(P＜0.05)between the combined administration group and PB21 and Dex alone.GAP43 and CGRP expression levels in synovial tissue were detected.The results indica-ted that PB21 and Dex alone could lower protein expression levels at 4 and 24 h at the two time points,and that the PB21+Dex group could still significantly lower GAP43 and CGRP expression levels at 48 h.At the 48 h time point,the PB21+Dex group was statistically significant when compared to the PB21 and Dex alone administration group(P＜0.05).Conclusion In summary low dose dexamethasone can prolong the analgesic effect of PB21 on KOA rats,which is connected to reducing the expression of pain related proteins CGRP and GAP43.

[Objective]The clinical characteristics and the possible risk factors were explored for the low triiodothyronine syndrome(LTS)in elderly patients with chronic heart failure(CHF),and the risk prediction model of LTS was established.[Methods]For this research,291 elderly patients with CHF were selected as sample and retrospectively reviewed was used as analytical method.According to the thyroid function of admission patients,two groups including LTS group(n=107)and normal thyroid function group(n=184)were divided.The general information and biochemical indicators of patients were collected and recorded,and the risk factors for LTS were assigned scores,in which numerical variables(except age)were grouped by median.The chi-squared test was used for statistical analysis of each variable,and multivariate regression model was used to analyze the independent risk factors of LTS in elderly patients with CHF,then the nomogram model for LTS was established based on the results from the final regression analysis.Furthermore,the prediction model was evaluated using C-index,calibration curve and receiver operating characteristic(ROC)curve.[Result]Serum creatinine(Scr),C-reactive protein(CRP),interleukin-6(IL-6)and the cardiac functional grading according to the New York Heart Association(NYHA)were positively correlated with LTS(OR values were 1.893,2.356,1.021 and 1.815,respectively,P<0.05),serum Albumin(Alb)was negatively correlated with LTS(OR=0.412,P<0.05).This means that,the LTS was easily occurred as the serum Alb level declined.When introduce the above statistically significant variables into nomogram obtained the C index with 0.807[95%CI=(0.757,0.856)].The calibration curve verified by internal verification showed that the calibration degree of this prediction model was well calibrated.ROC curve analysis showed that the prediction model was well differentiated.[Conclusion]The Scr,CRP,IL-6,Alb and cardiac functional grading in elderly CHF patients may be risk factors for incidence of LTS,while serum Alb may be a protective factor for LTS.Based on the above risk factors,the nomogram model for predicting the occurrence of LTS in elderly CHF patients had good differentiation and accuracy,and can provide guidance for clinical individualized prevention and treatment.