Based on the high-fat diet-induced hyperlipidemia rat model, this study aimed to evaluate the lipid-lowering effect of Arisaema Cum Bile and explore its mechanisms, providing experimental evidence for its clinical application. Biochemical analysis was used to detect serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), triglycerides(TG), and total cholesterol(TC) to assess the lipid-lowering activity of Arisaema Cum Bile. Additionally, 16S rDNA sequencing and metabolomics techniques were employed to jointly elucidate the lipid-lowering mechanisms of Arisaema Cum Bile. The experimental results showed that high-dose Arisaema Cum Bile(PBA-H) significantly reduced serum ALT, AST, LDL-C, TG, and TC levels(P<0.01), and significantly increased HDL-C levels(P<0.01). The effect was similar to that of fenofibrate, with no significant difference. Furthermore, Arisaema Cum Bile significantly alleviated hepatocyte ballooning and mitigated fatty degeneration in liver tissues. As indicated by 16S rDNA sequencing results, PBA-H significantly enhanced both alpha and beta diversity of the gut microbiota in the model rats, notably increasing the relative abundance of Akkermansia and Subdoligranulum species(P<0.01). Liver metabolomics analysis revealed that PBA-H primarily regulated pathways involved in arachidonic acid metabolism, vitamin B_6 metabolism, and steroid biosynthesis. In summary, Arisaema Cum Bile significantly improved abnormal blood lipid levels and liver pathology induced by a high-fat diet, regulated hepatic metabolic disorders, and improved the abundance and structural composition of gut microbiota, thereby exerting its lipid-lowering effect. The findings of this study provide experimental evidence for the clinical application of Arisaema Cum Bile and the treatment of hyperlipidemia.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Metabolomics ; Hyperlipidemias/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Hypolipidemic Agents/pharmacology* ; Liver/metabolism* ; Humans ; Alanine Transaminase/metabolism* ; Triglycerides/metabolism* ; Aspartate Aminotransferases/metabolism*

OBJECTIVES: To investigate the application value of thromboelastography (TEG) in assessing coagulation function in children with severe hemophilia A (HA) after emicizumab (EMI) therapy. METHODS: A retrospective analysis was performed on the activated partial thromboplastin time (APTT) and TEG testing results of 17 children with severe HA before and after EMI treatment at Shenzhen Children's Hospital from January 2023 to July 2024. Correlation analysis was conducted between coagulation factor VIII (FVIII) equivalent activity and reaction time (R value) measured by TEG. RESULTS: After EMI treatment, the mean bleeding rate for children with severe HA was 1.6 events per year, with 15 children (88%) without spontaneous bleeding or joint bleeding. The children with severe HA showed a significant reduction in APTT after EMI treatment (P<0.05), with a significantly shorter APTT than the normal control group (P<0.05). There was no correlation between APTT and FVIII equivalent activity after treatment (P>0.05). After EMI treatment, TEG parameters, including R value, kinetic time, alpha angle (α), maximum amplitude, clot strength, and coagulation index, shifted from a hypocoagulable state before treatment to a nearly normal state after treatment (P<0.05). The R value demonstrated a strong negative correlation with FVIII equivalent activity (r=-0.758, P<0.05). CONCLUSIONS The bleeding condition of children with severe HA can be effectively controlled after EMI treatment. Routine APTT testing cannot reflect true coagulation function, whereas TEG testing is clinically valuable in assessing the coagulation function of children with severe HA undergoing EMI treatment.
Humans ; Thrombelastography ; Hemophilia A/physiopathology* ; Male ; Child ; Antibodies, Bispecific/therapeutic use* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Blood Coagulation/drug effects* ; Child, Preschool ; Retrospective Studies ; Female ; Partial Thromboplastin Time ; Adolescent ; Infant

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective:To explore the effectiveness of patient participation and Internet plus in fall prevention management strategies of elderly inpatients and analyze the causes of falls, so as to provide a basis for continuous improvement in fall prevention to investigate their continuous improvement.Methods:A pre- and post-control study was conducted. Totally 8 480 elderly inpatients hospitalized in the Department of Internal Medicine from 1 June 2020 to 31 May 2021 in Chenzhou NO. 1 People′s Hospital were selected by convenient sampling as the control group, and 8 662 elderly inpatients hospitalized in the Department of Internal Medicine from 1 June 2021 to 31 May 2022 were in the experimental group. The routine fall prevention measures were used in the control group, and on this basis, the experimental group formulated and implemented fall prevention management strategies involving patients based on the patient participation framework "informing, participating, empowering, cooperating, and electronic information support" and introduced Internet plus. Then the differences between the two groups in terms of the incidence of falls and the satisfaction rate of nursing care were compared.Results:The experimental group included 8 662 cases (5 110 males and 3 552 females) with (73.96 ± 8.78) years old, while the control group included 8 480 cases (4 918 males and 3 562 females) with (74.11 ± 8.59) years old. The incidence of falls in experimental group (0.092%, 8/8 662) was lower than that in control group (0.224%, 19/8 480), and the difference was statistically significant ( χ 2=4.71, P<0.05); the nursing care satisfaction rate of experimental group (98.880%, 8 565/8 662) was higher than that of control group (96.450%, 8 179/8 480), and the difference also was statistically significant ( χ 2=106.50, P<0.01); the analysis of the fall causes of the patients revealed that the toilet squatting commode was an important hidden risk of falls in elderly patients. Conclusions:Fall prevention management strategies based on patient participation can reduce the incidence of falls in elderly patients and improve the satisfaction rate of nursing care. Patient participation introduced "Internet plus" can prevent patient falls. The root causes of patient falls will continue to change, and care managers should continually track real-time changes in the root causes of falls to identify problems, develop and adjust prevention strategies accordingly, and pay attention to the importance of infrastructure in the safety of older patients.

Objective:To study the clinical safety and validity of retrograde new endoscopic field of vision in miniature pigs.Methods:6 live miniature pigs were selected as study subjects,En-doscopic Retrograde New View(ERNV)was selected.The performance,image quality and intraoper-ative and postoperative complications were evaluated.To evaluate whether all the experimental ani-mals could complete the relevant endoscopy.Verify ERNV's operating performance,including whether the duodenoscope can enter the biliary tract smoothly,and made sure whether the injection,suction,and instrument channels were unobstructed.Choledochoscope image clarity,color resolu-tion,image deformation and distortion,accurate evaluation of lumen conditions and clear observation of mucosal surface conditions were analyzed.Whether there were operant injuries such as bleeding and perforation,as well as adverse events such as respiratory depression and cardiac arrest.The sur-vival status and adverse reactions of all pigs were observed.Results:The choledochoscope was successfully inserted into the bile duct of 6 miniature pigs.The product had good operation perfor-mance and could enter the bile duct through the duodenoscope smoothly.The injection,suction and instrument channels were relatively smooth.In addition,the endoscopic images are clear,with better color resolution,and without image deformation and distortion,which can realize accurate evaluation of the conditions in the lumen and observe the mucosal surface conditions more clearly.No bile duct stenosis or dilatation occurred in all miniature pigs,and the bile duct mucosa was smooth,without hyperemia and edema,and no abnormal thickening or bending of mucous vessels.During the exami-nation,there were no operational injuries such as bleeding and perforation,and no adverse events such as respiratory depression and cardiac arrest occurred.The vital signs of all miniature pigs tended to be stable after operation,and the survival state was good,and there were no complications such as cholangitis,bleeding and perforation.Conclusion:ERNV has good clinical safety and efficacy,ex-cellent operation performance and excellent image quality,and is worthy of clinical application.

Objective To investigate the progression of breast cancer in mice induced by chronic binding stress and the regulatory mechanism of Xiaoyao SAN based on TGF-β1/CD147 signal pathway.Methods 40 BABL/c mice were randomly divided into tumor group,model group,Xiaoyaosan group and Mifepristone group,and then 4T1 cell line was inoculated into the armpits of each group of mice.After Tumor formation,mice in all groups except tumor group were subjected to chronic restraint stress for 21 days.Meanwhile,mice in Xiaoyaosan and Mifepristone groups were gavaged with the corresponding drugs,and mice in the other two groups were gavaged with normal saline.After the modeling,the mice were sacrificed after anaesthesia.The weight and volume of the tumors and visceral index of the mice were measured.The contents of serum tumor markers(CA199,CEA,VEGF),serum neurotransmitters(DA and CORT),and inflammatory mediators(TGF-β1 and IL-10)in tumor tissues were detected by Elisa.The expressions of iNOS and Arg-1,the polarization markers of macrophages,and the expressions of CD147 and its downstream signaling molecules MMP2,MMP9 and VEGF in tumor tissues were all detected by immunohistochemistry and Western blot.Results Compared with tumor group,in model group,tumor weight and volume,serum CA199,CEA,VEGF,CORT content,tumor TGF-β1 and IL-10 content were significantly increased;visceral index and serum DA content were significantly reduced;the expression of M2-type polarization marker Arg-1 in tumor macrophages was significantly increased,while the expression of M1-type polarization marker iNOS was significantly decreased;the expressions of CD147 and its downstream signaling molecules MMP2,MMP9 and VEGF were significantly increased.Both Xiaoyaosan and mifepristone could effectively reverse the above changes.Conclusion The mechanism of chronic restraint stress promoting breast cancer progression in mice is related to the increased release of TGF-β1 from M2-type polarization of tumor-associated macrophages,which activates CD147 and its downstream related signals.Xiaoyaosan could relieve the M2-type polarization of macrophages caused by increased corticosterone under stress conditions,reduce the production of TGF-β1,inhibit CD147 and its downstream signal,and thus inhibit the progression of breast cancer caused by chronic restraint stress in mice.

OBJECTIVE To study the protective effect and mechanism of Bupleurum chinense polysaccharides （BCP） on acute liver injury （ALI） in mice. METHODS Overall 40 mice were randomly divided into normal group， model group， positive control group （Baogan tablet， 550 mg/kg）， BCP high-dose and low-dose groups （400， 100 mg/kg）， with 8 mice in each group. The drug was administered intragastrical once a day for 7 days. One hour after the last administration， except for the normal group， mice in other groups were injected with 20 mg/kg concanavalin A solution through the tail vein to establish ALI model. After injection of concanavalin A solution for 12 h， the liver and spleen indexes of mice were measured， and the pathological changes of liver and spleen tissue were observed； the serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT） and lactate dehydrogenase （LDH） were detected， and the levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in liver tissue were detected. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in serum and liver tissue of mice were determined， as well as the protein expression levels of nuclear factor-κB （NF-κB）， Toll-like receptor 4 （TLR4）， nuclear factor erythroid 2-related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） in liver tissue were also detected. RESULTS Compared with the normal group， the liver tissue of mice in the model group was necrotic and infiltrated with inflammatory cells； spleen enlargement， increased bleeding and decreased lymphocytes were observed， liver and spleen indexes were increased significantly （P＜0.01）； the serum levels of AST， ALT and LDH， the levels of TNF-α， IL-6 and IL-1β in serum and liver tissue， as well as the MDA level， protein expressions of TLR4， NF- κB and HO-1 in liver tissue were all increased significantly （P＜0.05 or P＜0.01）. The levels of SOD and protein expression of Nrf2 in liver tissue were all decreased significantly （P＜0.05）. Compared with the model group， the pathological damages of the liver and the spleen tissues in mice alleviated in BCP high-dose and low-dose groups， and most of liver and spleen indexes， the above indexes of serum and liver tissue were reversed significantly （P＜0.05 or P＜0.01）. CONCLUSIONS BCP has a protective effect on ALI， the mechanism of which may be related to the inhibition of TLR4/NF-κB signaling pathway and the activation of the Nrf2/HO-1 signaling pathway.

Taking " harmony of body and spirit" as the theoretical core in Huangdi Neijing and the functional nature and executive structure of the five emotions system as clues, this paper explores and analyzes the relevant theories of the five emotions system in ancient Chinese medicine literature. It is found that the five emotions system is a highly ordered and integrated collection of five functional states. It often resides in the five zang viscera, it operates between the meridians and the xuanfu through the elevation and movement of the qi, and it is the pivotal point for the operation of the qi and blood of the organism, the interactive conduction of information, and the unity of form, emotion, and qi. Therefore, this paper starts from the point of view of system science. It is proposed that the primordial spirit exercises control over the five emotions and the five emotions provide nutrition to the primordial spirit, and that the two are not " islands of information" but have a dynamic and hierarchical internal connection. The executive structure of the five emotions system, namely, the meridians, the xuanfu, and the five zang viscera, is the pivot, and it is recognized that the operation of the five emotions system is a process with self-organizing characteristics and orderly and eternal motion. We think of the qi, blood, ying, and essence as the basis of occurrence, the meridian as the execution channel, and the xuanfu as the place for the spiritual mechanism to enter and exit; the five zang viscera serve as a dwelling place, and ministerial fire serves as the source of energy. This paper serves as reference for future research related to the executive structure of the five emotions system of traditional Chinese medicine.

Pathological mood changes,mainly depression,occurring during the diagnosis and treatment of breast cancer are referred to as breast cancer-related depression(BCRD).Numerous epidemiological and clinical studies have confirmed that BCRD is a complex condition that is difficult to treat and has a poor prognosis.Most existing clinical treatments involve the use of postoperative chemotherapy for breast cancer,and antidepressant drugs,which treat breast cancer and depression as two independent diseases and have various disadvantages such as low efficiency and strong adverse reactions.Traditional Chinese Medicine(TCM)has a unique value in the prevention and treatment of BCRD via its ability to regulate multiple pathways and targets using multiple components at the same time.In this paper,we review the mechanism of BRCD and the therapeutic mechanisms of TCM from the aspects of neurological disorders,inflammatory immune response,and intestinal flora disorders,with a view to providing references for the clinical application and research of TCM in the treatment of BCRD.

Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying mechanisms.In vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-β(TGF-β).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated his-topathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw form.Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)pathway.Of note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and caspase9.small interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3.In conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mecha-nism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.