Bone metastasis,as a common terminal event in patients with advanced malignant tumors,significantly impacts patients'quality of life and survival prognosis,posing a major clinical challenge in the field of oncology.With the deepening understanding of tumor biology,the treatment paradigm for bone metastasis has progressively shifted from traditional palliative care to precise targeted interventions.Currently,clinical treatment strategies have demonstrated diversified development,with various therapeutic approaches-including radiotherapy,immunotherapy,bone-modifying agents,and small-molecule targeted drugs—achieving notable clinical progress.However,existing treatment regimens still face challenges such as significant interindividual variability in efficacy,frequent drug resistance,and prominent adverse effects.This article systematically reviews the latest advances in precision therapy for bone metastasis,provides an in-depth analysis of the strengths and limitations of different treatment strategies,and offers perspectives on future research directions and therapeutic prospects,aiming to provide reference for optimizing clinical practice and promoting translational research.

To investigate the association between obesity-related metabolic indices and the risk of knee osteoarthritis(KOA) in middle-aged and older Chinese adults(≥45 years) using data from the China Health and Retirement Longitudinal Study(CHARLS).

In recent years, research on the quality and safety detection of bear bile powder has mainly involved three aspects. First, the identification of active components and substitutes. Quantitative analysis of bile acids and other components is performed using HPLC, HPLC-tandem mass spectrometry, and other techniques, combined with near-infrared spectroscopy, X-ray diffraction, and polymerase chain reaction to identify adulteration. Isotope fingerprint analysis and glycosylation modification detection are used to distinguish natural products from biosynthetic substitutes, revealing significant differences in δ13C values and the proportion of specific glycosylation modifications between natural bear bile powder and synthetic products. Second, the detection of veterinary drug residues, mainly based on ultra-high performance liquid chromatography-tandem mass spectrometry, which can screen over 100 types of residues, but targeted purification strategies are needed to address interference from the bile acid matrix. Thirdly, heavy metal detection, mainly using inductively coupled plasma mass spectrometry and atomic absorption spectrometry, has revealed that contamination is associated with the breeding environment, with significant regional differences. Related detection technologies are gradually evolving from single-target analysis to multi-modal and intelligent approaches. Existing research faces issues, such as matrix effect interference, lack of international standards, and ethical controversies. It is suggested that future efforts should focus on the interdisciplinary application of detection technologies, develop rapid detection methods such as non-invasive monitoring and microfluidic chips, promote the standardization and equivalence evaluation of synthetic alternatives, and establish a full-chain quality control system integrating spatially resolved mass spectrometry imaging, artificial intelligence, and big data.

ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

Objective To analyze the effect of serum lactate dehydrogenase(LDH)and β2-microglobulin(β2-MG)on therapeutic efficacy of the first-line chemotherapy regimen for Waldenstr?m Macroglobulinemia(WM).Methods Data were collected from 113 WM patients admitted from March 2019 to February 2024.All patients completed the established first-line chemotherapy regimen and were divided into the response group(n=85)and the non-response group(n=28).The general data between the two groups were compared,with a focus on analyzing the risk factors for non-response to first-line chemotherapy in WM patients and evaluating the predictive value of serum LDH and β2-MG for the efficacy of first-line chemotherapy.Result The non-responsive group had a higher risk of prognosis based on International Prognostic Scoring System(IPSS),a higher rate of MYD88 L265P mutation,higher TP53 deletion/mutation ratio,and higher proportion of bone marrow lymphoplasmacytic cells,as well as higher serum LDH and β2-MG expression than the response group(P＜0.01).Multivariate logistic regression analysis revealed that risk factors for non-response to first-line chemotherapy in WM patients included a high-risk prognosis based on IPSS,an increased proportion of bone marrow lymphoplasmacytic cells,and higher rate of MYD88 L265P mutation and TP53 deletion/mutation,as well as elevated serum LDH and β2-MG levels(P＜0.05).The area under the curve of serum LDH and β2-MG for predicting the risk of non-response to first-line chemotherapy in WM patients was 0.796 and 0.783 respectively.Through interaction analysis,serum LDH and β2-MG had a positive interaction effect on non-response to chemotherapy in WM patients.Conclusion The non-response to first-line chemotherapy in WM patients is related to abnormal increase in serum LDH and β2-MG.Pre-chemotherapy detection of LDH and β2-MG level has certain predictive value for the risk of non-response to chemotherapy,and the simultaneous increase of both may lead to a higher risk of non-response to chemotherapy.

Bone metastasis,as a common terminal event in patients with advanced malignant tumors,significantly impacts patients'quality of life and survival prognosis,posing a major clinical challenge in the field of oncology.With the deepening understanding of tumor biology,the treatment paradigm for bone metastasis has progressively shifted from traditional palliative care to precise targeted interventions.Currently,clinical treatment strategies have demonstrated diversified development,with various therapeutic approaches-including radiotherapy,immunotherapy,bone-modifying agents,and small-molecule targeted drugs—achieving notable clinical progress.However,existing treatment regimens still face challenges such as significant interindividual variability in efficacy,frequent drug resistance,and prominent adverse effects.This article systematically reviews the latest advances in precision therapy for bone metastasis,provides an in-depth analysis of the strengths and limitations of different treatment strategies,and offers perspectives on future research directions and therapeutic prospects,aiming to provide reference for optimizing clinical practice and promoting translational research.

Objective To analyze the effect of serum lactate dehydrogenase(LDH)and β2-microglobulin(β2-MG)on therapeutic efficacy of the first-line chemotherapy regimen for Waldenstr?m Macroglobulinemia(WM).Methods Data were collected from 113 WM patients admitted from March 2019 to February 2024.All patients completed the established first-line chemotherapy regimen and were divided into the response group(n=85)and the non-response group(n=28).The general data between the two groups were compared,with a focus on analyzing the risk factors for non-response to first-line chemotherapy in WM patients and evaluating the predictive value of serum LDH and β2-MG for the efficacy of first-line chemotherapy.Result The non-responsive group had a higher risk of prognosis based on International Prognostic Scoring System(IPSS),a higher rate of MYD88 L265P mutation,higher TP53 deletion/mutation ratio,and higher proportion of bone marrow lymphoplasmacytic cells,as well as higher serum LDH and β2-MG expression than the response group(P＜0.01).Multivariate logistic regression analysis revealed that risk factors for non-response to first-line chemotherapy in WM patients included a high-risk prognosis based on IPSS,an increased proportion of bone marrow lymphoplasmacytic cells,and higher rate of MYD88 L265P mutation and TP53 deletion/mutation,as well as elevated serum LDH and β2-MG levels(P＜0.05).The area under the curve of serum LDH and β2-MG for predicting the risk of non-response to first-line chemotherapy in WM patients was 0.796 and 0.783 respectively.Through interaction analysis,serum LDH and β2-MG had a positive interaction effect on non-response to chemotherapy in WM patients.Conclusion The non-response to first-line chemotherapy in WM patients is related to abnormal increase in serum LDH and β2-MG.Pre-chemotherapy detection of LDH and β2-MG level has certain predictive value for the risk of non-response to chemotherapy,and the simultaneous increase of both may lead to a higher risk of non-response to chemotherapy.

Objective To construct a predictive model for septic shock based on the propensity score matching (PSM) method and validate its effectiveness. Methods A total of 114 patients with sepsis were enrolled as study objects, and were divided into septic shock group (40 patients) and sepsis group (74 patients) according to whether they developed septic shock. PSM was performed with a ratio of septic shock to sepsis of 1∶2, resulting in the inclusion of 30 patients in the septic shock group and 60 patients in the sepsis group after matching. The levels of C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), serum amyloid A (SAA), soluble endothelial protein C receptor (sEPCR), endothelial cell-specific molecule 1 (ESM-1), clusterin (CLU), and the Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score and Sequential Organ Failure Assessment (SOFA) score at admission were compared between the two groups. Cox proportional hazards regression analysis was used to identify the factors influencing septic shock, and a predictive model for septic shock was constructed and internally validated using the receiver operating characteristic (ROC) curve. Kaplan-Meier survival curves were plotted to analyze the differences in survival prognosis among patients with different expression levels of the indicators. Results After matching, there were no statistically significant differences in general information between the two groups (P>0.05). At admission, the septic shock group had higher levels of serum PCT, CRP, SAA, IL-6, sEPCR, ESM-1, and higher APACHE Ⅱ and SOFA scores, as well as a lower level of serum CLU compared with the sepsis group (P < 0.05). Cox regression analysis showed that PCT, CRP, SAA, IL-6, sEPCR, ESM-1, APACHE Ⅱ score, and SOFA score were independent risk factors for septic shock (P < 0.05), while CLU was an independent protective factor (P < 0.05). The predictive model for septic shock, constructed based on these factors, showed an internal validation accuracy of 94.44%, an area under the curve of 0.950, a sensitivity of 93.33%, and a specificity of 96.67%. Dead patients had higher levels of PCT, CRP, SAA, IL-6, sEPCR, ESM-1, and higher APACHE Ⅱ and SOFA scores, as well as a lower level of CLU at admission compared with survivors (P < 0.05). Compared with patients with low expression levels or low scores, patients with high expression levels of PCT, CRP, SAA, IL-6, sEPCR, ESM-1, and high APACHE Ⅱ and SOFA scores had higher fatality rates, while patients with high CLU expression levels had a lower fatality rate (P < 0.05). Conclusion The serum biomarkers including PCT, CRP, SAA, IL-6, sEPCR, ESM-1, CLU, and the APACHE Ⅱ and SOFA scores in sepsis patients are closely related to the occurrence of septic shock and survival prognosis. The predictive model constructed by combining these indicators can accurately predict the occurrence of septic shock.

BACKGROUND:Mechanical factors can affect the angiogenic ability of vascular endothelial cells.How the vessel number affects the hydrodynamic properties of microvessels remains to be clarified. OBJECTIVE:To investigate the influence of vessel number on the hydrodynamics of vascular networks based on computational fluid dynamics. METHODS:Three three-dimensional models of vascular network with different vessel numbers were constructed using the Geometry module of ANSYS 19.0 software,and then the vascular network was meshed to tetrahedral elements in Mesh module.The vascular network was assumed to rigid wall without slip,and the blood was assumed to laminar,viscous,and incompressible Newtonian fluid.Blood density,velocity,and a series of blood viscosity coefficients were also established.The Navier-Stokes equation was used for calculation.Hydrodynamic properties of different parts of vascular network with different vessel numbers were analyzed and compared. RESULTS AND CONCLUSION:The streamline,velocity,and mass flow all had the same trend in the vascular network,that is,the outlet and inlet were higher and the middle junction of vascular network was lower.The more the number of vessels,the thinner the blood flow lines in each part of the vascular network.Also,the velocity,mass flow,and wall shear decreased with the increase of the number of blood vessels.Therefore,the changes in vessel number could influence the hydrodynamic environment in the vascular network.Computational fluid dynamics indicates that the changes in vessel numbers can influence the hydrodynamic properties of blood,and provides a new idea for treating bone hypoperfusion-induced diseases(fracture nonunion,bone defect,osteoporosis,etc.)through tonifying kidney and activating blood circulation based on the coupling between angiogenesis and osteogenesis.