ObjectiveTo investigate the mechanism of salt processing of Psoraleae Fructus （PF） through modern analytical techniques and biotechnology， focusing on its effects related to hepatotoxicity and anti-osteoporosis activity. MethodsThe zebrafish model was utilized to evaluate the impact of PF and salt-processed Psoraleae Fructus （SPF） on the hepatotoxicity （using 134.17 ， 178.89， 268.34 mg·L^-1 as low， medium， and high dose groups of PF， 135.04， 180.06， 270.08 mg·L^-1 as low， medium， and high dose groups of SPF， respectively） and anti-osteoporotic activity （using 33.54 ， 67.08 and 134.17 mg·L^-1 as low， medium， and high dose groups of PF， 33.76， 67.52， 135.04 mg·L^-1 as low， medium， and high dose groups of SPF， respectively）， which was using alizarin red skull staining of zebrafish as an indicator of different batches of PF. The specific dosage of a batch of PF was taken as an example. Then ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry（UPLC-Q-TOF-MS） analysis was employed to identify the chemical composition of PF before and after salt processing， and PCA， OPLS-DA， and independent sample t-test were used to elucidating the compositional changes associated with the effects of salt processing on hepatotoxicity and anti-osteoporosis activity. ResultsUnder specific conditions， PF induced notable hepatotoxicity in zebrafish while simultaneously demonstrating protective effect against prednisolone-induced osteoporosis. In comparison to PF， SPF showed alleviated hepatotoxicity while retaining significant anti-osteoporosis activity. UPLC-Q-TOF-MS analysis revealed that after salt processing， the overall chemical composition of PF showed a downward trend， with 69 components showing a decrease in content， represented by psoralen， and 13 components showing an increase， represented by 4′-O-methyl psoralen B. Further multivariate statistical analysis revealed 11 key differential components before and after salt processing of PF， including psoralen and bakuchiol. ConclusionSalt processing effectively diminishes hepatotoxicity without impairing therapeutic efficacy against osteoporosis of PF， which may be related to the compositional changes before and after salt processing of PF and provides key evidence to reveal the scientific significance of salt processing of PF.

High mobility group box protein 1(HMGB1)is one of the most widely expressed protein member in the HMGs family,which is well known for its involvement in the body inflammatory response.Previous researches have found that it plays a significant role in cell migration,immune identification and neuroprotection.Spinal cord injury is a disease that causes severe damage to the nervous system,and neural circuits are disrupted after a spinal cord injury,which leads to many conditions including ischemia and hypoxia,inflammatory responses,demyelinating lesions,and glial scar formation that are detrimental to nerve regeneration and repair,making it one of the most difficult diseases to treat in the modern spinal surgery field.HMGB1 is upregulated after spinal cord injury,thereby regulating neuroinflam-matory responses,and participating in the neuronal apoptosis,promoting neuronal regeneration,and inducing neural stem cell differentiation and migration,which plays an important role in the process of neural function recovery.This paper summarizes the structure and function of HMGB1,as well as its role in spinal cord injury,in order to provide direction for founding therapeutic target for neurological function recovery after spinal cord injury.

Objectives:To investigate the epidemiological characteristics and ethnic differences of cardiovascular-kidney-metabolic syndrome(CKM)among the Hani,Dai,Bai,and Lisu populations in Yunnan Province,and to provide evidence for developing effective prevention and control strategies for CKM.Methods:A cross-sectional survey was conducted among four ethnic minority groups.A total of 3 906 permanent residents aged 18 years and older were enrolled using a multistage cluster random sampling method.CKM stages(0-4)were defined based on the 2023 American Heart Association criteria,stages 3-4 were classified as advanced CKM.Descriptive statistics and chi-square tests were used to compare the prevalence of CKM stages across ethnic groups.Modified Poisson regression was applied to estimate relative risk(RR)and 95%confidence intervals(CI)for factors associated with advanced CKM.Results:The prevalence rates of CKM stage 1 and above among the Hani,Dai,Bai and Lisu ethnic groups were 80.1%,87.3%,84.8%and 67.8%,respectively.The prevalence of CKM was generally higher in males than in females,and the prevalence of CKM increased significantly with age.The Dai ethnic group had the highest prevalence of advanced CKM(24.7%,95%CI:22.1%-27.4%),while the Lisu ethnic group had the lowest prevalence of advanced CKM(13.7%,95%CI:11.5%-15.9%).Modified Poisson regression analysis showed that older age and higher body mass index were common risk factors for advanced CKM across all four ethnic groups.Additionally,except for the Lisu ethnic group,the other three ethnic groups had specific individual risk factors:among the Hani ethnic group,low educational attainment(RR=2.18,95%CI:1.12-4.25)and low income(RR=1.47,95%CI:1.00-2.18)were the primary risk factors of CKM.Among the Dai ethnic group,smoking(RR=1.60,95%CI:1.07-2.37)and a family history of cardiovascular disease(RR=1.61,95%CI:1.14-2.27)are the primary risk factors of CKM.Among the Bai ethnic group,male gender(RR=0.48,95%CI:0.29-0.79)was the primary risk factor of CKM.Conclusions:The prevalence of CKM stage 1 or higher is relatively high among the four minority ethnic groups in Yunnan province.There are significant differences in staging characteristics and primary risk factors across ethnic groups,necessitating the development of stratified,differentiated intervention strategies to achieve precise prevention and control and ethnic health equity in terms of CKM.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

In proton therapy,prompt gamma-ray imaging is considered as one of the most promising methods for assessing proton beam range.Prompt gamma-ray imaging detector evaluates the proton beam range based on the prompt gamma-ray distribution obtained by the prompt gamma-ray imaging system,which enables high-precision measurement of the proton beam range.Herein a proton beam range verification algorithm is designed for the newly developed prototype of the range verification detector(pixelated prompt gamma-ray imaging detector),which verifies the range estimation accuracy of the prototype for different phantoms and different energies of homogeneous media through Monte Carlo simulation.The results show that the accuracy of the proton beam range verification algorithm is within 0.5 mm of the safety margin error of the Bragg peak,and the measurement accuracy is significantly improved with the increase of the number of protons,indicating that the prototype algorithm is feasible for proton beam range verification.

Aim To investigate the intervention effect of Rehmannia radix water extract on bleomycin(BLM)-induced pulmonary fibrosis in mice combined with metabolomics and to reveal the potential mechanism,in order to provide new ideas for clinical treatment of pul-monary fibrosis.Methods Male C57BL/6N mice were randomly divided into the control group,model group,pirfenidone group(positive control,PFD,270 mg·kg-1),and low dose(DH-L,4.55 g·kg-1)group,medium dose(DH-M,9.1 g·kg-1)group and high dose(DH-H,18.2 g·kg-1)group of Rehman-nia.Except for the control group,BLM(5 mg·kg-1)was instilled into the trachea to establish the model of pulmonary fibrosis in the other groups.The survival rate,lung index and blood oxygen saturation of mice in each group were evaluated.HE and Masson staining were used to observe the pathological changes of lung tissue.WBP was used to detect lung function.Flow cytometry was used to detect the apoptosis of primary lung cells,ROS and immune cells.ELISA was used to detect the levels of fibrosis markers and inflammatory factors(α-SMA,collagen Ⅰ,collagen Ⅲ,TGF-β1,TNF-α,IL-1 β,and IL-6).Biochemical method was employed to detect the contents of GSH-Px,T-SOD and MDA.Liquid chromatograph mass spectrometer(LC-MS)metabolomics was used to analyze the changes of serum metabolic profile.Results Water extract of Re-hmannia significantly increased the survival rate,oxy-gen saturation and lung function of mice with pulmona-ry fibrosis,reduced the lung coefficient,ameliorated pathological damage and collagen deposition in lung tissue,reduced the levels of apoptosis and oxidative stress,and down-regulated the levels of inflammatory factors in lung tissue.It regulated the levels of metabo-lites such as bile acid metabolism,sphingolipid metabo-lism,and unsaturated fatty acid metabolism.Conclu-sions Water extract of Rehmannia inhibits lung injury and collagen deposition in mice with pulmonary fibrosis by inhibiting inflammatory response,which may be a-chieved by regulating the levels of inflammatory factors through the metabolic pathways of bile acid and sphin-golipid.

Aim To explore the effects of high glucose on KIAA0753 and CCSAP and the relationship between KIAA0753 and CCSAP and osteogenic differentiation and calcium signaling pathway under high glucose con-ditions.Methods Mouse embryonic osteoblast pre-cursor cells(MC3T3-E1)were induced by osteoblast medium with glucose concentrations of 5.5 and 25 mmol·L-1,and the protein expressions of KIAA0753 and CCSAP were detected by Western blot.The over-expressed plasmid was transfected into human embry-onic kidney cells(HEK-293T),and the interaction between KIAA0753 and CCSAP was detected by co-im-munoprecipitation.MC3T3-E1 cells were treated in the osteogenic medium with different glucose concentrations and induction times.Alkaline phosphatase(ALP)ac-tivity was detected with a kit.The expression of KI-AA0753,CCSAP,osteopontin,osteocalcin,and other proteins were assessed using Western blot.and then 5.5,25 mmol·L-1,and 25 mmol·L-1+OE-CCSAP three groups of MC3T3-E1 cells were set.The expression of KIAA0753,OCN,OPN protein,and ALP activity were detected successively.The diabetic mouse model dataset in Gene Expression Omnibus was used to screen differential genes for bioinformatics a-nalysis.MC3T3-E1 cells were set up in three groups,5.5,25 mmol·L-1,and 25 mmol·L-1+OE-KI-AA0753,respectively.The calcium/calmodulin-de-pendent protein kinase Ⅱ beta(CAMK2B)and phos-pholamban(PLN)were detected by Western blot.Re-sults Compared with the 5.5 mmol·L-1 group,25 mmol·L-1 inhibited the expression of KIAA0753 and CCSAP proteins in osteoblasts,and there was an inter-action between KIAA0753 and CCSAP.At the same time,25 mmol·L-1 also inhibited the expression of ALP,OPN,and OCN proteins in osteoblasts.Overex-pression of CCSAP at 25 mmol·L-1 up-regulated the expression of KIAA0753,OCN,OPN,and ALP.The differential genes of the diabetic mouse model were mainly concentrated in the aspects of"signal receptor and signal regulation".25 mmol·L-1 glucose inhibi-ted the expression of CAMK2B and PLN proteins in os-teoblasts,and overexpression of KIAA0753 at 25 mmol·L-1 upregulated the expression of CAMK2B and PLN proteins.Conclusions High glucose inhibits the expression of KIAA0753 and CCSAP protein,inhibits the osteogenic differentiation and calcium signaling in mouse embryonic osteoblast precursor cells,overex-pression of CCSAP saves the inhibitory effect of high glucose on osteogenic differentiation,and overexpres-sion of KIAA0753 reverses the inhibitory effect of high glucose on calcium signaling pathway.

Prostate cancer is one of the most common male urological malignancies,in which bone metastasis of desmo-plasia-resistant prostate cancer is an important stage in the progression of the disease,which seriously affects the quality of life and survival of patients.With the development of nuclide therapy technology in recent years,223-Ra,as a new type of alpha-targeted therapy,has shown good efficacy in the treatment of desmoplasia-resistant prostate cancer bone metastasis.The purpose of this pa-per is to review the characteristics,mechanism of action,treatment,and the main research results of its treatment of desmoplasia-resistant prostate cancer bone metastasis,and provide a comprehensive review of the clinical application of 223-Ra in the treatment of desmoplasia-resistant prostate cancer bone metastasis for the clinical application of 223-Ra in prostate cancer bone metastasis.

High mobility group box protein 1(HMGB1)is one of the most widely expressed protein member in the HMGs family,which is well known for its involvement in the body inflammatory response.Previous researches have found that it plays a significant role in cell migration,immune identification and neuroprotection.Spinal cord injury is a disease that causes severe damage to the nervous system,and neural circuits are disrupted after a spinal cord injury,which leads to many conditions including ischemia and hypoxia,inflammatory responses,demyelinating lesions,and glial scar formation that are detrimental to nerve regeneration and repair,making it one of the most difficult diseases to treat in the modern spinal surgery field.HMGB1 is upregulated after spinal cord injury,thereby regulating neuroinflam-matory responses,and participating in the neuronal apoptosis,promoting neuronal regeneration,and inducing neural stem cell differentiation and migration,which plays an important role in the process of neural function recovery.This paper summarizes the structure and function of HMGB1,as well as its role in spinal cord injury,in order to provide direction for founding therapeutic target for neurological function recovery after spinal cord injury.

Objectives:To investigate the epidemiological characteristics and ethnic differences of cardiovascular-kidney-metabolic syndrome(CKM)among the Hani,Dai,Bai,and Lisu populations in Yunnan Province,and to provide evidence for developing effective prevention and control strategies for CKM.Methods:A cross-sectional survey was conducted among four ethnic minority groups.A total of 3 906 permanent residents aged 18 years and older were enrolled using a multistage cluster random sampling method.CKM stages(0-4)were defined based on the 2023 American Heart Association criteria,stages 3-4 were classified as advanced CKM.Descriptive statistics and chi-square tests were used to compare the prevalence of CKM stages across ethnic groups.Modified Poisson regression was applied to estimate relative risk(RR)and 95%confidence intervals(CI)for factors associated with advanced CKM.Results:The prevalence rates of CKM stage 1 and above among the Hani,Dai,Bai and Lisu ethnic groups were 80.1%,87.3%,84.8%and 67.8%,respectively.The prevalence of CKM was generally higher in males than in females,and the prevalence of CKM increased significantly with age.The Dai ethnic group had the highest prevalence of advanced CKM(24.7%,95%CI:22.1%-27.4%),while the Lisu ethnic group had the lowest prevalence of advanced CKM(13.7%,95%CI:11.5%-15.9%).Modified Poisson regression analysis showed that older age and higher body mass index were common risk factors for advanced CKM across all four ethnic groups.Additionally,except for the Lisu ethnic group,the other three ethnic groups had specific individual risk factors:among the Hani ethnic group,low educational attainment(RR=2.18,95%CI:1.12-4.25)and low income(RR=1.47,95%CI:1.00-2.18)were the primary risk factors of CKM.Among the Dai ethnic group,smoking(RR=1.60,95%CI:1.07-2.37)and a family history of cardiovascular disease(RR=1.61,95%CI:1.14-2.27)are the primary risk factors of CKM.Among the Bai ethnic group,male gender(RR=0.48,95%CI:0.29-0.79)was the primary risk factor of CKM.Conclusions:The prevalence of CKM stage 1 or higher is relatively high among the four minority ethnic groups in Yunnan province.There are significant differences in staging characteristics and primary risk factors across ethnic groups,necessitating the development of stratified,differentiated intervention strategies to achieve precise prevention and control and ethnic health equity in terms of CKM.