Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

OBJECTIVE: This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease (NAFLD) in children with obesity. METHODS: We conducted a two-step case-control study. Ninety-three participants were subjected to whole-exome sequencing (exploratory set). Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing (validation set). RESULTS: In the exploratory set, 14 genes from the NAFLD-associated pathways were identified. In the validation set, after adjusting for sex, age, and body mass index, ECI2 rs2326408 (dominant model: OR = 1.33, 95% CI: 1.02-1.72; additive model: OR = 1.22, 95% CI: 1.01-1.47), C6orf201 rs659305 (dominant model: OR = 1.30, 95% CI: 1.01-1.69; additive model: OR = 1.21, 95% CI: 1.00-1.45), CALML5 rs10904516 (pre-ad dominant model: OR = 1.36, 95% CI: 1.01-1.83; adjusted dominant model: OR = 1.40, 95% CI: 1.03-1.91; and pre-ad additive model: OR = 1.26, 95% CI: 1.04-1.66) polymorphisms were significantly associated with NAFLD in children with obesity ( P < 0.05). Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516, COX11 rs17209882, and SCD5 rs3733228 was optional ( P < 0.05), demonstrating a negative interaction between the three genes. CONCLUSION In the Chinese population, the CALML5 rs10904516, C6orf201 rs659305, and ECI2 rs2326408 variants could be genetic markers for NAFLD susceptibility.
Humans ; Non-alcoholic Fatty Liver Disease/genetics* ; Child ; Male ; Female ; Genetic Predisposition to Disease ; Case-Control Studies ; Exome Sequencing ; Adolescent ; Polymorphism, Single Nucleotide ; Obesity/complications* ; Pediatric Obesity/complications* ; China

Objective To study the distolingual space of mandibular molars in adult patients with different sagittal skeletal patterns,and to analyze the main bony anatomical sites that restrict molar distalization,in order to provide guidance for the treatment plan of mo-lar distalization.Methods A total of 97 adult patients according to the inclusion criteria were selected from the Department of Ortho-dontics,the Affiliated Stomatological Hospital of Nanjing Medical University.The patients were divided into skeletal Class Ⅰ group(n=28),skeletal Class Ⅱ group(n=49)and skeletal Class Ⅲ group(n=20)according to the ANB angle.CBCT of the patients were im-ported into Dolphin software for 3D reconstruction.The width of the distal root of the second molar,the width of alveolar bone,the dis-tance between the most convex point of the distal and lingual side of the distal root and the inneredge of the lingual cortex of the mandi-ble were measured at the 2,4,and 6 mm plane from the root furcation to the root apex.Statistical analysis was performed using SPSS 26.0 software,and univariate analysis of variance and LSD-t test were used to compare the difference.Results Root width was significantly narrower than alveolar bone width at all measurement planes(P＜0.01).Molar distolingual space in patients with different sagittal skeletal patterns was smaller than molar distal space,and the size of the space gradually decreased with the deepening of the measurement level,reaching the minimum value at the R4 and R6 measurement planes.Measurement results of this study showed that at the R6 level,the molar distolingual space in skeletal Class Ⅱ group was the minimum(2.30±2.45)mm;on the contrary,skeletal Class Ⅲ group was the maximum(4.17±2.38)mm.Conclusion When designing the plan of molar distalization in clinical practice,CBCT should be used,and more attention should be paid to the lingual alveolar bone mass of the mandibular molar.It is a safe and effective treatment method for skeletal Class Ⅰ and Ⅲ patients with mild to moderate dental crowding.

Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)pre-sents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2％dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2％ DSS-induced Rag1-/-mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage indepen-dently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned me-dium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.

This review summarized the pathogenesis of coagulation dysfunction, high-risk factors for bleeding and thrombosis, monitoring indicators for anticoagulation, drug therapy for coagulation dysfunction, assessment and nursing interventions for coagulation dysfunction in patients supported by extracorporeal membrane oxygenation, with the aim of providing evidence-based strategies for anticoagulation management in extracorporeal membrane oxygenation patients.

To characterize human antibodies against low-calcium response V(LcrV)antigen of Yersinia pestis,the mono-clonal antibodies were screened and assayed.Antibody gene was derived from peripheral blood mononuclear cells of the vaccin-ees immunized by plague subunit vaccine in phase Ⅱb clinical trial.Human ScFv antibody library was constructed by phage dis-play.After panning library by using recombinant LcrV antigen,antibody variable genes were sequenced and converted into IgG1 format to evaluate its binding specificity and relevant parameters.An anti-plague human ScFv antibody library was estab-lished contained 7.54× 108 independent clones.After panning by LcrV antigen,3 human antibodies named as RV-B4,RV-D1 and RV-E8,respectively,were identified.Using indirect enzyme-linked immunosorbent assay(ELISA)and Western blot(WB),the specific bindings of the mAbs to LcrV antigen were confirmed.The dissociation constant(KD)of them to LcrV is 2.1 nmol/L,1.24 nmol/L and 42 nmol/L,respectively.Minor protective efficacy was found among 3 human antibodies in Y.pestis 141-infected mice.Three anti-LcrV monoclonal antibodies generated from immunized vaccinees were binding specific antibod-ies and could not block plague infection in mice.These antibodies are the potential candidate reagents for basic research of plague immunity and the application of plague diagnosis.

Objective: To investigate the factors affecting depression and anxiety symptoms among the elderly, so as to provide the basis for promoting mental health among the elderly. Methods: The elderly aged 60 years and above in Ningbo City, Zhejiang Province were recruited using the multistage stratified random sampling method from June to August 2022, and demographic information, lifestyle and self-rated health status were collected by questionnaires. The symptoms of depression and anxiety were assessed by the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7), respectively. The presence of depressive and anxiety symptoms was determined when both the PHQ-9 score and the GAD-7 score were 10 points and higher. Factors affecting depressive and anxiety symptoms were identified using a multivariable logistic regression model. Results: A total of 7 771 individuals were surveyed, including 3 490 males (44.91%) and 4 281 females (55.09%), and had a mean age of (72.11±6.79) years. The prevalence of depression and anxiety symptoms was 2.05%. Multivariable logistic regression analysis identified residence (urban area, OR=0.316, 95%CI: 0.201-0.498), sedentary duration (<3 h/d, OR=0.349, 95%CI: 0.232-0.525; 3-5 h/d, OR=0.458, 95%CI: 0.313-0.671), physical activity (≥3 times/week, OR=0.551, 95%CI: 0.373-0.815), sleep quality (poor, OR=2.491, 95%CI: 1.738-3.571), social isolation (OR=1.688, 95%CI: 1.148-2.481) and self-rated health (poor, OR=5.857, 95%CI: 3.547-9.671; normal, OR=1.903, 95%CI: 1.234-2.937) as the influencing factors for depression and anxiety symptoms among the elderly. Conclusion The prevalence of depression and anxiety symptoms among the elderly is associated with residence, sedentary duration, sleep quality, physical activity, social interactions and self-rated health status.

Objective To investigate the role of programmed necrosis pathway in testicular tissue damage in rats with erectile dysfunction(ED)and the mechanism of sildenafil intervention.Methods An ED rat model was established by high-fat chow feeding,and the rats were randomly divided into model group,experimental group,interleukin 18 group,and experimental+interleukin 18 group;10 rats were randomly selected as the normal control group.The experimental group was gavaged with 20 mg·kg-1sildenafil;the interleukin 18 group was injected intraperitoneally with 0.2 μg·kg-1interleukin 18 recombinant protein;the experimental+interleukin 18 group was gavaged with an equal amount of sildenafil,and the experimental+interleukin 18 group was injected intraperitoneally with an equal amount of interleukin 18 recombinant protein;the normal control and model groups were given with an equal amount of 0.9％NaCl by gavage and intraperitoneally injected with an equal amount of saline;and the experimental group was injected with an equal amount of 0.9％NaCl.Interleukin 18 group was gavaged with an equal amount of 0.9％NaCl,and the five groups of rats were administered once a day at regular intervals for 14 consecutive days.Reverse transcription polymerase chain reaction(RT-qPCR)and Western blotting were used to detect the expression of receptor-interacting protein kinase 1(RIP1),receptor-interacting protein kinase 3(RIP3),mixed-spectrum kinase structural domain-like protein(MLKL),and calcium-calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)in rat testis tissues.Results The relative expression levels of RIP1 protein in the normal control group,model group,experimental group,interleukin 18 group and experimental+interleukin 18 group were 0.58±0.05,0.99±0.09,0.71±0.05,1.23±0.07 and 0.81±0.07;the relative expression levels of RIP3 protein were 0.61±0.05,1.05±0.10,0.77±0.04,1.19±0.07 and 0.84±0.08,respectively;the relative expression levels of MLKL protein were 0.63±0.05,1.13±0.08,0.79±0.05,1.30±0.02 and 1.00±0.04,respectively;the relative expression levels of CaMK Ⅱ protein were 0.54±0.04,1.12±0.07,0.77±0.05,1.36±0.04 and 1.00±0.07;the differences of the above indexes were statistically significant when the model group was compared with the normal control group,the experimental group was compared with the model group,the interleukin 18 group was compared with the model group,and the experimental+interleukin 18 group was compared with the interleukin 18 group(all P＜0.05).Conclusion The RIP1/RIP3-mediated necroptosis pathway plays multiple regulatory roles in testicular injury in ED rats,and sildenafil may improve testicular function in rats by inhibiting the above necroptosis signaling pathway.

Phosphatase and tensin-homolog deleted on chromosome 10 (PTEN) is an important cancer suppressor gene. Its pathogenic mutation leads to PTEN hamartoma tumor syndrome (PHTS), a rare syndrome also known as Cowden syndrome, which is relevant to early-onset hereditary breast cancer (BC). In this paper, we report three patients with unilateral multicentric BC and synchronous and metachronous bilateral BC who harbored PTEN gene mutations, and summarize the clinical manifestations, pathological characteristics, diagnosis, treatment and follow-up outcomes to provide reference for management of PTEN gene mutation-related BC among the Cowden syndrome population.

Objective This study aims at establishing a teaching catalog and content for breast rare dis-eases and developing the syllabus for the breast rare disease using integrated multimodality of case-/problem-/resource-based learning(CBL+PBL+RBL).Methods By conducting bibliometrics co-occurrence analysis,we collected 6291 articles on breast rare disease published from January,1975 to June,2024.Additionally,we re-trieved the Textbook on Rare Diseases,the Catalog of Chinese Rare Disease,and Second Batch of Rare Dis-ease Catalog and then decided the teaching content.Results From 16,387 keywords,1000(6.1％)keywords were identified through co-occurrence analysis,including 50(0.3％)candidate diseases.These were classified into three categories:rare primary breast diseases,rare genetic mutation-related diseases associated with breast cancer,and rare systemic multi-system diseases involving the breast.From the candidate list,20(0.1％)rare primary breast diseases were further selected for their notable clinical teaching significance,and significant multi-systemic diseases affecting the breast,whether related to gene mutations or not.Teaching plans were draf-ted using a diversified parallel teaching approaches,taking into account the characteristics of different diseases and the focus of different teaching methods.Conclusions This study initiated the development of the teaching content for breast rare diseases and developed the teaching syllabus using the CBL+PBL+RBL integrated multi teaching model and targeting each rare breast disease for the critical point for teaching.