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.

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 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.

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.

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 explore the clinical effects of two kinds of nasal bone reductors used for shortened and displaced overlapping external nasal fracture reduction under nasal endoscopy and the impact on ventilation function. Methods:From January 2020 to February 2022, 82 patients with shortened and displaced overlapping external nasal fractures diagnosed and treated in the Department of Otolaryngology, the Second People's Hospital of Hefei were collected as the study subjects. The patients were divided into control group（41 cases） and observation group（41 cases） by random number table method. Both groups underwent closed reduction under nasal endoscopy. The control group was treated with traditional straight nasal bone reductor, and the observation group was treated with gun-shaped hook type nasal bone reductor. The success rate of reduction, follow-up rate, clinical effect, and complications were compared between the two groups. The visual analogue scale（VAS） was used to evaluate the aesthetic effect and functional recovery. Rhinomanometry and acoustic rhinometry were used to evaluate nasal ventilation function. Results:The success rate of one-time reduction in the observation group was significantly higher than that in the control group, and the nasal reduction adaptation time was shorter than that in the control group（P<0.05）. There was no significant difference in the follow-up rate of 95.12% and 92.68% between the two groups. The success rate of one-time reduction in observation group was significantly higher than that in the control group, and the adaptation time for nasal reduction in observation group was shorter than that in the control group（P<0.05）. There was no significant difference in the follow-up rate of 95.12% and 92.68% between the two groups in six months after surgery. the total clinical effective rate in observation group was higher than that in the control group（94.87% vs 76.32%, P<0.05）. After surgery, the scores of nasal aesthetics, nasal congestion and olfactory function in both groups were significantly lower compared with the preoperative scores. All the scores in the observed group were lower than that in the control group（P<0.05）. After surgery, there were significant increases in the minimum cross-sectional area of nasal cavity, volume of nasal cavity and total nasal expiratory volume in both groups. Above indicators in observation group were significantly greater than that in control group. The nasal exhalation and inhalation resistance was significantly lower than that before operation, and the resistance in observation group was significantly lower than that in control group（P<0.05）. The total incidence of complications was lower than that in observation group（P<0.05）. Conclusion:The application of gun-shaped hook-type nasal bone reductor in patients with shortened and displaced overlapping external nasal fractures has better success rate of one-time reduction, adaptation time of nasal reduction and treatment outcome. Moreover, it has more advantages in aesthetic effect of nasal appearance, nasal ventilation function and reduction of complications.
Humans ; Nasal Bone/injuries* ; Male ; Female ; Endoscopy/methods* ; Adult ; Treatment Outcome ; Nose/surgery* ; Middle Aged

ObjectiveTo explore the association between short-term exposure to atmospheric fine particulate matter （PM_2.5） and ozone （O₃） and systemic inflammatory indicators in patients with pneumonia， and to identify the susceptible populations. MethodsFrom September 2018 to April 2020， data of 1 480 patients admitted for pneumonia was collected from a tertiary hospital in Taiyuan City. Generalized additive models （GAMs） were used to explore the associations between PM_2.5 and O₃ exposure and inflammatory indicators of patients with pneumonia； and to explore the susceptibility factors and susceptible populations to PM_2.5 and O₃ exposures through stratified analyses. ResultsThe short-term exposure to PM_2.5 was associated with changes in peripheral blood C-reation protein （CRP）， erythrocyte sedimentation （ESR）， easinophil （EOS）， neutrophil （NEU） and neutrophil-lymphocyte ratio （NLR） in patients with pneumonia， and there were different degrees of hysteresis effects， with the effect values reaching a maximum at lag03， lag03， lag0， lag03， lag03， respectively， which were 4.13% （95%CI： 0.43%‒7.84%）， 3.10% （95%CI： 0.24%‒5.97%）， 5.27% （95%CI： 3.12%‒7.42%）， 1.85% （95%CI： 0.36%‒3.34%）， and 2.53% （95%CI： 0.53%‒4.74%） for every 10 μg·m^-3 of PM_2.5. The changes in O₃ concentration were associated with the elevation of peripheral blood PCT and ESR in patients with pneumonia， and their effect values all reached the maximum at lag01 d， every 1 μg·m^-3 of O₃ elevation increased by 0.38% （95%CI： 0.04%‒0.73%） and 0.47% （95%CI： 0.19%‒0.76%）， respectively. Stratified analyses showed that the associations of PM_2.5 with peripheral blood CRP， ESR， NEU， and NLR in pneumonia patients were more significant in males， the elderly， and those with onset in the cold season； the associations of O₃ with peripheral blood PCT and ESR in pneumonia patients were more significant in the elderly and those with onset in the warm season， and the peripheral blood CRP and PCT in female patients with pneumonia were more susceptible to the changes of O₃. ConclusionShort-term exposure to atmospheric PM_2.5 and O₃ are positively associated with changes in inflammatory indicators in patients with pneumonia， and the effects of PM_2.5 on patients with pneumonia are more extensive than those of O₃， with a longer lag effect. In addition， elderly patients with pneumonia are more sensitive to air pollution， male patients with pneumonia are more sensitive to PM_2.5， and female patients with pneumonia are more sensitive to O₃. Cold and warm seasons can exacerbate the effects of PM_2.5 and O₃ on inflammatory indicators in patients with pneumonia， respectively， and the patients must be protected well.