OBJECTIVE To study the improvement effect and mechanism of Tripterygium wilfordii multiglucoside （TWM） on nephrotic syndrome in rats. METHODS The nephrotic syndrome model was established by intravenous injection of adriamycin via the tail vein. The modeling rats were randomly divided into the model group （distilled water）， prednisone group （10 mg/kg）， and TWM high- and low-dose groups （10 and 5 mg/kg， respectively）. Additionally， blank group （distilled water） without model induction was established. Each group consisted of 9 rats. Rats in each group were administered the corresponding drugs or distilled water by gavage， once a day， for 6 consecutive weeks. The histopathological morphology of kidney tissues in rats was observed； the levels of 24-hour urinary protein （24 h-UTP） and serum biochemical indicators [albumin （ALB）， blood urea nitrogen （BUN）， serum creatinine （SCr）， cholesterol （CHOL）， and triglyceride （TG）] in rats were determined； the levels of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in kidney tissue of rats were determined； expressions of hypoxia-inducible factor-1α （HIF-1α）/microRNA-155-5p （miR-155-5p）/nuclear factor erythriod 2- related factor 2 （Nrf2） signaling pathway-related mRNA and protein in the renal tissues of rats were detected. RESULTS Compared with the blank group， the rats in the model group exhibited disordered renal tissue structure， with a small amount of glomerular necrosis and edema of the renal tubular epithelial cells. 24 h-UTP， serum levels of SCr， BUN， CHOL and TG， MDA content， mRNA and protein expressions of HIF-1α and Keap1 as well as the expression of miR-155-5p in renal tissues were increased significantly （ P ＜0.05）. Serum level of ALB， SOD level in renal tissue as well as mRNA and protein expressions of Nrf2 were decreased significantly （ P ＜0.05）. Compared with the model group， TWM high-dose and low-dose groups exhibited significant improvements in renal injury， with notable reversals in the levels of the above quantitative indicators （ P ＜0.05）. CONCLUSIONS TWM can alleviate oxidative stress-induced damage and thereby improve nephrotic syndrome in rats by regulating the HIF-1α/miR-155-5p/Nrf2 signaling pathway.

This study aims to explore the protective effect of Chaihu Jia Longgu Muli Decoction on rats with heart failure after myocardial infarction, and to clarify its possible mechanisms, providing a new basis for basic research on the mechanism of classic Chinese medicinal formula-mediated inflammatory response in preventing and treating heart failure induced by apoptosis after myocardial infarction. A heart failure model after myocardial infarction was established in rats by coronary artery ligation. The rats were divided into sham group, model group, and low, medium, and high-dose groups of Chaihu Jia Longgu Muli Decoction, with 10 rats in each group. The low-dose, medium-dose, and high-dose groups of Chaihu Jia Longgu Muli Decoction were given 6.3, 12.6, and 25.2 g·kg~(-1) doses by gavage, respectively. The sham group and model group were given an equal volume of distilled water by gavage once daily for four consecutive weeks. Cardiac function was assessed using color Doppler echocardiography. Myocardial pathology was detected by hematoxylin-eosin(HE) staining, apoptosis was measured by TUNEL assay, and mitophagy was observed by transmission electron microscopy. The levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and N-terminal pro-B-type natriuretic peptide(NT-proBNP) in serum were detected by enzyme-linked immunosorbent assay(ELISA). The expression of apoptosis-related proteins B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), and cleaved caspase-3 was detected by Western blot. Additionally, the expression of phosphorylated nuclear transcription factor-κB(NF-κB) p65(p-NF-κB p65)(upstream) and nuclear factor kappa B inhibitor alpha(IκBα)(downstream) in the NF-κB signaling pathway was assessed by Western blot. The results showed that compared with the sham group, left ventricular ejection fraction(LVEF) and left ventricular short axis shortening(LVFS) in the model group were significantly reduced, while left ventricular end diastolic diameter(LVEDD) and left ventricular end systolic diameter(LVESD) increased significantly. Myocardial tissue damage was severe, with widened intercellular spaces and disorganized cell arrangement. The apoptosis rate was increased, and mitochondria were enlarged with increased vacuoles. Levels of TNF-α, IL-1β, and NT-proBNP were elevated, indicating an obvious inflammatory response. The expression of pro-apoptotic factors Bax and cleaved caspase-3 increased, while the anti-apoptotic factor Bcl-2 decreased. The expression of p-NF-κB p65 was upregulated, and the expression of IκBα was downregulated. In contrast, the Chaihu Jia Longgu Muli Decoction groups showed significantly improved of LVEF, LVFS and decreased LVEDD, LVESD compared to the model group. Myocardial tissue damage was alleviated, and intercellular spaces were reduced. The apoptosis rate decreased, mitochondrial volume decreased, and the levels of TNF-α, IL-1β, and NT-proBNP were lower. The expression of pro-apoptotic factors Bax and cleaved caspase-3 decreased, while the expression of the anti-apoptotic factor Bcl-2 increased. Additionally, the expression of p-NF-κB p65 decreased, while IκBα expression increased. In summary, this experimental study shows that Chaihu Jia Longgu Muli Decoction can reduce the inflammatory response and apoptosis rate in rats with heart failure after myocardial infarction, which may be related to the regulation of the IκBα/NF-κB signaling pathway.
Animals ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Myocardial Infarction/physiopathology* ; Male ; NF-kappa B/genetics* ; Heart Failure/etiology* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; NF-KappaB Inhibitor alpha/genetics* ; Humans ; Tumor Necrosis Factor-alpha/genetics*

OBJECTIVE To investigate the effects of Tripterygium wilfordii multiglycoside （TWM） on renal injury in diabetic nephropathy （DN） rats through tumor protein p53/microRNA-214 （miR-214）/UNC-51-like kinase 1 （ULK1） axis. METHODS Male SD rats were randomly divided into normal group （n＝6） and modeling group （n＝28）； the modeling group was fed with high fat and high glucose plus intraperitoneal injection of streptozotocin to establish DN model. The modeled rats were randomly divided into model group， valsartan group [8.33 mg/（kg·d）] and TWM group[6.25 mg/（kg·d）]， with 8 rats in each group. Rats in each group were gavaged with the corresponding medication or normal saline， once a day， for 6 consecutive weeks. After the last medication， liver and renal function indexes [24 h urinary total protein （24 h-UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr）， albumin （ALB）， alanine transaminase （ALT）]， blood lipid indexes （triglycerides， total cholesterol） and blood glucose index （fasting blood glucose） in urine/blood sample of rats were detected in each group. Renal pathologic change was observed， protein and mRNA expressions of p53， ULK1， Beclin-1 and microtubule-associated protein 1 light chain 3 （LC3）， and expression of miR-214 in renal tissue were also determined. RESULTS Compared with the normal group， the renal tubular epithelium of rats in the model group showed obvious edema， cell swelling， accompanied by lymphocyte infiltration； the levels of 24h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 in rats in the model group and administration groups were significantly increased or up-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1， Beclin-1 protein and mRNA were significantly decreased or down-regulated （P＜0.01）. Compared with the model group， the histopathological damage of the kidney in rats was improved in administration groups； the levels of 24 h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 were all significantly decreased or down-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1 and Beclin-1 protein and mRNA were significantly increased or up-regulated （P＜0.01）. CONCLUSIONS TG can alleviate renal damage in DN rats， and improve their liver and renal function， as well as glucose and lipid levels. These effects may be related to the regulation of the p53/miR-214/ULK1 axis and the restoration of cellular autophagy.

OBJECTIVES: This study aimed to investigate the clinical characteristics of deciduous fused teeth and their inherited permanent-tooth performance type by using panoramic radiographs. METHODS: A total of 14 404 panoramic radiographs of 3- to 6-year-old children with deciduous dentition were collected from January 2023 to July 2024. The incidence of deciduous fused teeth was observed, and the abnormality of permanent teeth was recorded. SPSS 24.0 software was used for statistical analysis. RESULTS: The incidence of deciduous fused teeth was 3.06% (441/14 404). The order of dental position was as follows: mandibular deciduous incisors and cusp teeth fused (58.18%) > mandibular deciduous central and lateral incisors fused (30.91%) > maxillary deciduous central and lateral incisors fused (8.89%) > deciduous incisors and supernumerary teeth fused (2.02%). Deciduous fused teeth were found in 226 boys and 215 girls, with no significant difference between the sexes (P>0.05). We observed one pair (87.76%, 387/441) and two pairs (12.24%, 54/441) of fused teeth (54/441), respectively. A total of 287 pairs of fusion teeth on the right side more than 208 pairs on the left side, and the difference between them was statistically significant (P<0.01). More fusion teeth existed in mandibular deciduous teeth (443 pairs) than in maxillary ones (54 pairs), and the difference between them was statistically significant (P<0.01). More unilateral deciduous teeth (387 subjects) were found than bilateral ones (54 subjects), and the difference between them was statistically significant (P<0.01). Three types of deciduous fused teeth with inherited permanent teeth were observed as follows: 1) 49.49% (245/495) of inherited permanent teeth was absent, 2) 46.67% (231/495) of inherited permanent teeth was not absent, and 3) the number of fused permanent teeth accounted for 3.84% (19/495). CONCLUSIONS The incidence of deciduous fused teeth was 3.06%, mostly occurring in the lower anterior teeth region, with no gender difference. One pair of fused teeth is commonly observed, more often on the right than the left. These fusions occur more frequently in the mandible than the maxillary, and unilateral cases are more common than bilateral ones. Deciduous fused teeth had a certain impact on inherited permanent teeth. Pediatric dentists should pay attention to and closely observe whether any abnormality exists in the permanent dentition for early detection to prevent the harm caused by deciduous fused teeth.
Humans ; Tooth, Deciduous/abnormalities* ; Male ; Child ; Female ; Child, Preschool ; Dentition, Permanent ; Radiography, Panoramic ; Fused Teeth/diagnostic imaging* ; Incisor/diagnostic imaging* ; Tooth, Supernumerary/diagnostic imaging* ; Incidence ; Mandible

Objective:To discuss the efficacy of temporomandibular joint disc anchoring(TMJDA)in the treatment of anterior disc displacement without reduction(ADDWoR)from clinical and imaging perspectives,in order to improve the clinicians'understanding of this surgical approach.Methods:Twenty-one ADDWoR patients who underwent TMJDA were retrospectively collected,involving a total of 25 temporomandibular joints(TMJs).The maximum mouth opening,visual analogue scale(VAS)score for pain,and Helkimo index were measured preoperatively,1 month postoperatively,and 6 months postoperatively in all the patients.Postoperative complications and satisfaction questionnaires were designed for the patients to self-evaluate the efficacy,and their magnetic resonance imaging(MRI)findings were assessed.Results:Compared with preoperative period,the maximum mouth opening at 1 month and 6 months postoperatively was significantly increased(P<0.05);compared with 1 month postoperatively,the maximum mouth opening at 6 months postoperatively was significantly increased(P<0.05).Compared with preoperative period,the VAS scores at 1 month and 6 months postoperatively were significantly decreased(P<0.05);compared with 1 month postoperatively,the VAS score at 6 months postoperatively was significantly decreased(P<0.05).Compared with preoperative period,the percentages of the patients with Di 0 and DiⅠ scores were significantly increased(P<0.05),while those with DiⅡand DiⅢ scores were significantly decreased(P<0.05),indicating significant improvement in TMJ function after surgery.Among the 21 ADDWoR patients,14(66.67%)were satisfied and 7(33.33%)were basically satisfied.Compared with preoperative period,the disc length was significantly increased postoperatively(P<0.01),while no significant difference was observed in condylar height(P>0.05);all displaced discs were repositioned postoperatively;among the 25 joints,23(92.00%)were evaluated as"excellent"and 2(8.00%)were evaluated as"good".No patients experienced postoperative facial nerve injury,local alopecia,surgical area depression,salivary fistula,or Frey syndrome;3 patients(3 joints)developed numbness in the preauricular area within 24 hours postoperatively,which resolved by the 6-month follow-up.Conclusion:TMJDA for the treatment of ADDWoR can stably reposition the disc,significantly improve mouth opening and pain levels,with a low incidence of postoperative complications.

To investigate the transcriptionally regulatory mechanism of the senp8 promoter in yellow cat-fish(Pelteobagrus fulvidraco);this study used P.fulvidraco as the research subject.Dual-luciferase re-porter assay and electrophoretic mobility shift assay were employed to analyze the functional activity of the promoter;coupled with in vivo experiments.The results indicated that the 2 045 bp senp8 promoter se-quence contained key transcription factor binding sites such as SP1;TATA-Box;CCAAT-Box;SREBP1;PPARα;and PPARγ.The binding sites of SREBP1(-901/-910 bp);PPARα(-1 291/-1 308 bp);and PPARγ(-1 292/-1 306 bp)in the senp8 promoter positively regulate its activity;and oleic acid or palmitic acid promote this binding.Furthermore;high-fat feeding promoted the expression of the senp8 gene and its protein in the liver of P.fulvidraco;oleic acid or palmitic acid treatment significantly en-hanced the activity of the senp8 promoter;and this enhancement could be achieved through the regulatory effects of SREBP1;PPARα;and PPARγ response elements.Additionally;high-fat feeding influenced the mRNA and protein expression levels of genes related to deSUMOylation modification in the liver of P.fulvidraco.This study provides new insights into the relationship between deSUMOylation modification and the regulation of lipid metabolism in the vertebrates.

Objective To investigate the effects of Sini Powder on serum hypothalamic-pituitary-adrenal(HPA)axis-related hormones and inflammatory factors in liver cancer mice with comorbid depression,and to evaluate its effect on depressive behavior and tumor proliferation activity.Methods Forty-eight specific pathogen-free female C57BL/6 mice were randomly assigned to either a blank(n=8)or model group(n=40).The modeling group was subjected to chronic unpredictable mild stress(CUMS)for six weeks.Both groups underwent orthotopically transplanted liver tumor surgery at the end of the fourth week of CUMS treatment.At the end of the sixth week of CUMS treatment,color Doppler ultrasonography was used to observe tumor formation in the orthotopic transplantation liver tumors,and the tail suspension test was used to assess depressive behavior.Non-tumor-bearing and deceased mice were excluded.The remaining model group mice were stratified by tail suspension immobility time and randomly assigned to the following groups:model group(distilled water),Fluoxetine group(5.0 mg/kg),and Sini Powder low-dose,medium-dose,and high-dose groups(5.2,10.4,and 20.8 g/kg,respectively),with six mice per group.The treatments were administered once daily for 21 consecutive days.After treatment,depressive behaviors were assessed using the open field,tail suspension,and forced swimming tests.The proliferation status of the orthotopic liver transplantation tumor was evaluated by measuring the size of the tumor,observing pathological changes in the tumor tissue through hematoxylin and eosin staining,and detecting the positive cell rate of proliferating cell nuclear antigen(Ki-67)in the tumor tissue using immunohistochemistry.The levels of HPA axis-related hormones in serum,such as corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),corticosterone(CORT),as well as inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)were measured using an enzyme-linked immunosorbent assay.Western blotting was used to assess mitogen-activated protein kinase(MAPKs)phosphorylation and the expression of nuclear factor-κB(NF-κB),NOD-like receptor family pyrin domain-containing receptor 3(NLRP3),and cysteine aspartic protease-1(Caspase-1)in orthotopic tumors.Results Compared with the blank group,the model group showed reduced total distance traveled in open field test,prolonged immobility times in the tail suspension and forced swimming tests(P<0.05,P<0.01),indicating successful establishment of the liver cancer with comorbid depression mice model.Also,the model group showed increased orthotopic tumor volume(P<0.01),and elevated serum CRH,ACTH,CORT,TNF-α,IL-1β,and IL-6 levels(P<0.01).The phosphorylation of MAPKs in tumor tissues was suppressed(P<0.01),while NF-κB,NLRP3,and Caspase-1 expression levels were downregulated(P<0.01).Compared with the model group,Sini Powder medium-and high-dose groups exhibited increased total distance traveled in the open field test(P<0.05),reduced forced swimming test and prolonged total distance traveled in open field test(P<0.01),while Sini Powder high-dose group showed reduced immobility times in the tail suspension test(P<0.05).Also,Sini Powder low-dose,medium-dose,and high-dose groups showed slower tumor growth,histological changes,including vacuolization and necrosis,decreased Ki-67 positive cell rate(P<0.01),and reduced serum CRH,ACTH,CORT,TNF-α,IL-1β,and IL-6 levels(P<0.05).Additionally,the phosphorylation of MAPKs in tumor tissues was suppressed(P<0.01),and NF-κB,NLRP3,and caspase-1 expression levels were downregulated(P<0.01).Conclusion Sini Powder may alleviate depressive behaviors and suppress tumor proliferation activity in liver cancer mice with comorbid depression by modulating MAPKs activation,inhibiting NF-κB,NLRP3,and Caspase-1 expressions,and reducing serum inflammatory factors and HPA axis-related hormones levels.

OBJECTIVE To study the chemical constituents in the root bark of Schisandra sphenanthera and their cytotoxic activ-ities.METHODS The compounds were isolated and purified by silica,Sephadex LH-20 and semi preparative-HPLC and the chem-ical structures were identified by 1 H-NMR,13 C-NMR and MS data analysis.The cytotoxic activities of the compounds were deter-mined by MTT method.RESULTS Twenty lignans were isolated and deduced as:Matairesinol(1),2-Hydroxy-2-(3′,4′-di-hydroxyphenyl)methyl-3-(3″,4″-dimethoxyphenyl)methyl-gamma-butyrolactone(2),(+)-Nortrachelogenin(3),2-Hydroxy-2-(4′-O-β-D-glucopyranosyl-3′-hydroxyphenyl)methyl-3-(3″,4″-dimethoxyphenyl)methyl-γ-butyrolactone(4),Nortracheloside(5),Burselignan(6),(+)-Cycloolivil(7),5-Methoxy-(+)-isolariciresinol(8),(-)-Isolariciresinol 3α-O-β-D-glucopyranoside(9),(+)-9-O-β-D-Glucopyranosyl lyoniresinol(10),(-)-Secoisolariciresinol(11),Licarin A(12),Cedrusin(13),Mataires-inol 4′-O-β-D-glucopyranoside(14),Pregomisin(15),Meso-dihydroguaiaretic acid(16),7S,8R-Erythro-4,9,9′-trihydroxy-3,3′-dimethoxy-8-O-4′-neolignan-7-O-β-D-glucopyranoside(17),Gomisin M2(18),Gomisin M3(19),Pinoresinol(20).Com-pounds 1-3,12,15,16,18 and 19 showed cytotoxic activity against A549,HCT116 and SW620 cell lines with IC50 values ranging from 1.4 to 22.9 μmol·L-1.CONCLUSION Compounds 1-4,6-12,14,17-19 are isolated from the plant for the first time,com-pounds 1-3,12,15,16,18 and 19 exhibit cytotoxic activities.

ObjectiveTo explore the effects of Kaixuan Jiedu core prescription （KXJD） on sphingolipid metabolism in the mouse model of imiquimod-induced psoriasis-like skin lesions. MethodsThirty-seven male C57BL/6J mice were randomly assigned into five groups： healthy control （n=11）， model （n=11）， methotrexate （MTX， n=5）， low-dose （15.21 g·kg^-1） KXJD （n=5）， and high-dose （30.42 g·kg^-1） KXJD （n=5）. Psoriasis-like skin lesions were induced in mice with 62.5 mg 5% imiquimod cream applied on the back. The KXJD groups and MTX group were treated with 0.2 mL corresponding decoction and MTX， respectively， by gavage daily， while the other groups were given an equal volume of normal saline by the same way. After 5 days of treatment， back skin lesions were collected. Firstly， healthy control and model mice were selected for tandem mass tag （TMT） quantitative proteomics （control vs model=3 vs 3） and targeted lipid metabolomics （control vs model=11 vs 11）. Then， the binding degree between core components and target proteins was predicted via network pharmacology and molecular docking. Finally， an animal experiment was performed to decipher the specific regulation mechanism of KXJD on sphingolipid metabolism. Immunohistochemistry was employed to determine the expression level of sphingosine-1-phosphate （S1P）， and Western blot was employed to determine the expression levels of sphingosine kinase 2 （SPHK2） and monocyte chemotactic protein-1 （MCP-1）. ResultsTMT proteomics and targeted lipid metabolomics suggested that sphingolipid metabolism was active in the psoriatic skin， and key proteases ［serine palmitoyltransferase， long chain base subunit 2 （SPTLC2）， SPHK2， delta（4）-desaturase sphingolipid 1 （Degs1）， and ceramide synthase 4 （CerS4）］ and 8 sphingolipid metabolites （including ceramides， sphingol， sphingomyelin， and glycosphingolipid） expressed abnormally （P<0.05） compared with those in the healthy skin. The molecular docking results indicated that the binding energy between the active components （quercetin， kaempferol， and luteolin） in KXJD and key proteins involved in sphingolipid metabolism was less than-8 kal·mol^-1. Further experimental verification showed elevated expression levels of SPHK2， S1P， and MCP-1 in psoriatic skin compared with healthy skin （P<0.05）， and KXJD down-regulated the expression levels of SPHK2， S1P， and MCP-1 compared with the model group （P<0.05）. ConclusionThis study indicates that there is an imbalance in sphingolipid metabolism in psoriatic skin lesions. KXJD may reduce psoriasis-like lesions in mice by regulating sphingolipid metabolism via the SPHK2/S1P/MCP-1 pathway.