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.

BACKGROUND: The American Heart Association (AHA) introduced the concept of cardiovascular-kidney-metabolic (CKM) health and stage, reflecting the interaction among metabolism, chronic kidney disease (CKD), and the cardiovascular system. However, the association between CKM stage and the long-term risk of cardiovascular disease (CVD) has not been validated. This study aimed to evaluate the long-term CVD risk associated with CKM health metrics and CKM stage using data from a population-based cohort study. METHODS: In total, 5293 CVD-free participants were followed up to around 13 years in the Chinese Multi-provincial Cohort Study (CMCS). Considering the pathophysiologic progression of CKM health metrics abnormalities (comprising obesity, central adiposity, prediabetes, diabetes, hypertriglyceridemia, CKD, and metabolic syndrome), participants were divided into CKM stages 0, 1, and 2. The time-dependent Cox regression models were used to estimate the cardiovascular risk associated with CKM health metrics and stage. Additionally, broader CVD outcomes were examined, with a specific assessment of the impact of stage 3 in 2581 participants from the CMCS-Beijing subcohort. RESULTS: Among participants, 91.2% (4825/5293) had at least one abnormal CKM health metric, 8.8% (468/5293), 13.3% (704/5293), and 77.9% (4121/5293) were in CKM stages 0, 1, and 2, respectively; and 710 incident CVD cases occurred during a median follow-up time of 13.3 years (interquartile range: 12.1 to 13.6 years). Participants with each poor CKM health metric exhibited significantly higher CVD risk. Compared with stage 0, the hazard ratio (HR) (95% confidence interval [CI]) for CVD incidence was 1.31 (0.84-2.04) in stage 1 and 2.27 (1.57-3.28) in stage 2. Significant interactive impacts existed between CKM stage and age or sex, with higher CVD risk related to increased CKM stages in participants aged <60 years or females. CONCLUSION These findings highlight the contribution of CKM health metrics and CKM stage to the long-term risk of CVD, suggesting the importance of multi-component recognition and management of poor CKM health in CVD prevention.
Humans ; Female ; Male ; Cardiovascular Diseases/etiology* ; Middle Aged ; Adult ; Cohort Studies ; Renal Insufficiency, Chronic/metabolism* ; Aged ; Risk Factors ; Metabolic Syndrome/metabolism* ; China ; East Asian People

OBJECTIVES: This study aimed to investigate the impact of foam macrophages (FMs) on the intracellular survival of Mycobacterium tuberculosis (MTB) and identify the molecular mechanisms influencing MTB survival. METHODS: An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival. RESULTS: Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate (cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival. CONCLUSIONS FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.
Mycobacterium tuberculosis/physiology* ; Transcriptome ; Metabolomics ; Foam Cells/microbiology* ; Humans ; Metabolome ; Tuberculosis/microbiology* ; Gene Expression Profiling

Objective To investigate whether O6-methylguanine-DNA methyltransferase(MGMT)interference combined with temozolomide(TMZ)could enhance the therapeutic effect of temozolomide on human drug-resistant melanoma cells A375/TMZ.Methods A375/TMZ cells were randomly divided into 4 groups,control group(normal culture),MGMTsiRNA group(200 nmol·L-1 MGMTsiRNA),experimental group(1 600 μmol·L-1 TMZ)and combined group(transfection of MGMTsiRNA followed by addition of 1 600 μmol·L-1 TMZ).After 24 h of culture,the proliferation of cells in each group was analyzed by cell counting kit-8 method.Western blotting was used to detect the expression levels of poly ADP-ribose polymerase(PARP),cleaved PARP(cleaved-PARP),DNA-dependent protein kinase catalytic subunit(DNA-PKcs)and nuclear factor kappa-B(NF-κB)proteins in the cells.The expression and distribution of NF-κB proteins in the cells were detected by immunofluorescence.Results Cell inhibition rates of control,MGMTsiRNA,experimental and combined groups were 0,(3.45±1.53)％,(51.24±2.73)％and(70.69±4.48)％;the relative expression levels of PARP protein were 0.45±0.08,0.47±0.06,0.33±0.04,0.14±0.03;the relative expression levels of the cleaved-PARP protein were 0.01±0.02、0.01±0.01、0.18±0.03 and 0.36±0.04;the relative expression levels of DNA-PKcs protein were 0.09±0.03,0.07±0.02,0.32±0.02 and 0.39±0.04;the relative expression levels of NF-κB protein were 0.35±0.04,0.36±0.05,0.20±0.02 and 0.15±0.02.Compared with experimental group or control group,the differences of above indexes were all statistically significant(all P＜0.05).Immunofluorescence analysis showed that the average fluorescence intensity of NF-κB in control group,MGMTsiRNA group,experimental group and combined group were(5.26±1.05)％,(7.58±1.18)％,(10.56±1.99)％and(15.47±2.61)％;and compared with the cells in control group and MGMTsiRNA group,combined group showed NF-κB was significantly increased in the nucleus of tumor cells,and the difference was statistically significant(all P＜0.01).Conclusion MGMTsiRNA combined with TMZ further promotes proliferation inhibition and apoptosis of drug-resistant melanoma A375/TMZ cells by TMZ.

Objective To investigate the mechanism of hippocampal neuronal plasticity of newborn neurons in the hippocampus by which exercise improves the fear and anxiety symptoms of post-traumatic stress disorder(PTSD).Methods Totally 40 C57BL/6J male mice were randomly divided into by control group(Ctrl)and PTSD group,the PTSD group was divided into a no-exercise group(PTSD),a low-intensity exercise group(L)and a high-intensity exercise group(H).The PTSD model mice were constructed by combining conditioned plantar-foot shock(CF)and single-session sustained stress(SPS).After the exercise intervention,the fear and anxiety levels of the mice were assessed using the conditioned fear test and the elevated cross maze test;Subsequently,the densities of the newborn mature neurons in dentate gyrus(DG)of hippocampus were detected by immunofluorescent double-labelling staining,and the newborn neuron morphology was marked by injecting retrovirus pRetro-U6-EF1-EGFP-3xFLAG-WPRE in DG of hippocampus to observe its morphology.The morphology of the newborn neurons was labelled to observe their dendritic length and the number of branch points;Meanwhile,the concentration level of adiponctin(APN)in the hippocampal area was determined by ELISA.Results The result showed that both high and low-intensity exercise interventions significantly reduced the freezing time of PTSD mice in the conditioned fear test,and in the elevated cross maze experiment,the residence time and the number of entries in the open arm of the mice in the H group increased significantly compared with those in the PTSD group,while the residence time and the number of entries in the closed arm were significantly reduced.In addition,both high and low-intensity exercise interventions significantly increased the surface density and dendritic length of newborn mature neurons in the hippocampal DG region of PTSD mice,and high-intensity exercise significantly increased the number of dendritic branching points,and the density of newborn mature neurons in the H group was more significantly increased compared with that in the L group.At the same time,the hippocampal APN concentration increased significantly in both L and H groups compared with the PTSD group,and it was more significant in the H group.Conclusion Exercises have an ameliorative effect on anxiety and fear symptoms in PTSD mice,and at the same time,it can increase hippocampal neuroplasticity and adiponctin secretion in PTSD mice,suggesting that the improvement of fear and anxiety symptoms in PTSD by exercise may be related to the increase of hippocampal neuroplasticity and APN secretion,and the improvement effect is better with high-intensity exercise.

When patients with malignant tumors are in the terminal stage of life, palliative care centered on the patient and their family plays a crucial role in improving the quality of life for advanced cancer patients and their families. As the core practitioners of palliative care, oncology nurses' cognition and practice of palliative care are closely related to the quality of palliative care for cancer patients. This paper analyzes the current state and influencing factors of the cognition and practice of palliative care from the perspective of oncology nurses and proposes improvement strategies, aiming to provide a reference for nursing managers to formulate targeted improvement programs and improve relevant systems.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective:To study the implementation progress of the prevention and control measures for drinking water-borne endemic fluorosis and the changing trend of fluorosis conditions in Inner Mongolia Autonomous Region, comprehensively evaluate the effectiveness of prevention and control measures, and provide a basis for the next step of prevention and control of the disease.Methods:In 2015 and 2023, a cross-sectional survey method was used to investigate the water improvement situation, the operation of water improvement projects, the detection of fluoride level in water, and the prevalence of dental fluorosis in children aged 8 to 12 in all affected villages of 11 leagues (cities) in the entire autonomous region. The prevention and control effect of drinking water-borne endemic fluorosis in the entire autonomous region was evaluated.Results:The water improvement rates of all affected villages in the entire autonomous region in 2015 and 2023 were 84.12% (8 218/9 769) and 95.38% (8 944/9 377), respectively. The qualified rates of water fluoride in the villages with water improvement in the entire autonomous region were 66.21% (5 441/8 218) and 91.00% (8 139/8 944), respectively. The water improvement rate and water fluoride qualification rate of water improvement villages in 2023 were both higher than those in 2015, and the differences were statistically significant (χ 2 = 652.96, 1 593.81, P < 0.001). The detection rates of dental fluorosis in children aged 8 to 12 years in the entire autonomous region in 2015 and 2023 were 9.26% (7 548/81 484) and 4.46% (3 441/77 155), respectively. The detection rate of dental fluorosis in children in 2023 was lower than that in 2015, and the difference was statistically significant (χ 2 = 1 418.20, P < 0.001). In 2015 and 2023, the total compliance rate of all affected villages in the entire autonomous region reaching the control standards were 57.94% (5 660/ 9 769) and 92.37% (8 662/9 377), respectively. The total compliance rate of all affected villages in 2023 was higher than that in 2015, and the difference was statistically significant (χ 2 = 3 010.38, P < 0.001). Conclusions:Compared with 2015, the prevention and control measures of drinking water-borne endemic fluorosis in Inner Mongolia Autonomous Region have been effectively implemented in 2023, with a significant decrease in the detection rate of dental fluorosis in children. However, there are still a few affected villages that have not achieved the control standards, and prevention and control work still need to be further strengthened.

Objective:To investigate the characteristics of the population of skeletal fluorosis patients in drinking-tea-borne endemic fluorosis (referred to as drinking-tea-borne fluorosis) areas in Inner Mongolia Autonomous Region (referred to as Inner Mongolia) and the influencing factors of treatment willingness, and to provide a basis for improving the prevention and control measures of drinking-tea-borne fluorosis and the treatment plan of skeletal fluorosis.Methods:From August to October 2022, a face-to-face questionnaire survey was conducted in key areas of drinking-tea-borne fluorosis in Inner Mongolia (administrative villages with an average daily intake of tea fluoride > 3.5 mg and skeletal fluorosis patients identified by the general survey of drinking-tea-borne fluorosis in Inner Mongolia in 2019), and to investigate the demographic, severity, and treatment status of patients with skeletal fluorosis, analyze the demographic characteristics of patients with skeletal fluorosis and the influencing factors of treatment willingness.Results:A total of 734 patients with skeletal fluorosis were investigated, including 543 mild cases, 125 moderate cases and 66 severe cases. The gender ratio of patients with skeletal fluorosis was 0.71 ∶ 1.00 (305/429), the age was concentrated in > 50 - 70 years old (70.57%, 518/734), the proportion of Mongolians was 94.28% (692/734), the proportion of herders was 97.68% (717/734), the educational level was mainly primary school (54.63%, 401/734), and the proportion of poor households and immigrants who had moved to their current residence was 7.08% (52/734) and 8.04% (59/734), respectively. The distribution of the severity of skeletal fluorosis in patients of different ages, genders, and educational levels was compared, and the differences were statistically significant ( P < 0.05). Fifty-three point two seven percent (391/734) of the patients had a willingness to undergo non-pharmacological treatment, of which 69.82% (273/391) had already started non-pharmacological treatment, with a treatment effectiveness rate of 73.99% (202/273). Sixty-five point two six percent (479/734) of the patients had a willingness to receive medication treatment, of which 7.31% (35/479) had already started medication treatment, with a treatment effectiveness rate of 54.29% (19/35). Zero point two seven percent (2/734) of the patients expressed a willingness to undergo surgical treatment, while no patients underwent surgical treatment. Multivariate logistic regression analysis showed that the age, ethnicity, occupation, educational level, poverty status, immigrants status, and the severity of skeletal fluorosis were all influencing factors of non-pharmacological treatment willingness ( P < 0.05). Occupation, educational level, poverty status, immigrants status, and the severity of skeletal fluorosis were all influencing factors of medication treatment willingness ( P < 0.05). Conclusions:Patients with skeletal fluorosis caused by tea drinking in Inner Mongolia are mainly from Mongolian ethnic groups, herders, middle-aged and elderly people, and those with a lower educational levels. The willingness of patients to receive treatment is influenced by various factors, and corresponding intervention measures can be formulated and taken based on these influencing factors to effectively improve the disease prevention awareness and treatment willingness of patients and the public.

When patients with malignant tumors are in the terminal stage of life, palliative care centered on the patient and their family plays a crucial role in improving the quality of life for advanced cancer patients and their families. As the core practitioners of palliative care, oncology nurses' cognition and practice of palliative care are closely related to the quality of palliative care for cancer patients. This paper analyzes the current state and influencing factors of the cognition and practice of palliative care from the perspective of oncology nurses and proposes improvement strategies, aiming to provide a reference for nursing managers to formulate targeted improvement programs and improve relevant systems.