A primary hallmark of pathological cardiac hypertrophy is excess protein synthesis due to enhanced translational activity. However, regulatory mechanisms at the translational level under cardiac stress remain poorly understood. Here we examined the translational regulations in a mouse cardiac hypertrophy model induced by transaortic constriction (TAC) and explored the conservative networks versus the translatome pattern in human dilated cardiomyopathy (DCM). The results showed that the heart weight to body weight ratio was significantly elevated, and the ejection fraction and fractional shortening significantly decreased 8 weeks after TAC. Puromycin incorporation assay showed that TAC significantly increased protein synthesis rate in the left ventricle. RNA-seq revealed 1,632 differentially expressed genes showing functional enrichment in pathways including extracellular matrix remodeling, metabolic processes, and signaling cascades associated with pathological cardiomyocyte growth. When combined with ribosome profiling analysis, we revealed that translation efficiency (TE) of 1,495 genes was enhanced, while the TE of 933 genes was inhibited following TAC. In DCM patients, 1,354 genes were upregulated versus 1,213 genes were downregulated at the translation level. Although the majority of the genes were not shared between mouse and human, we identified 93 genes, including Nos3, Kcnj8, Adcy4, Itpr1, Fasn, Scd1, etc., with highly conserved translational regulations. These genes were remarkably associated with myocardial function, signal transduction, and energy metabolism, particularly related to cGMP-PKG signaling and fatty acid metabolism. Motif analysis revealed enriched regulatory elements in the 5' untranslated regions (5'UTRs) of transcripts with differential TE, which exhibited strong cross-species sequence conservation. Our study revealed novel regulatory mechanisms at the translational level in cardiac hypertrophy and identified conserved translation-sensitive targets with potential applications to treat cardiac hypertrophy and heart failure in the clinic.
Animals ; Humans ; Cardiomegaly/physiopathology* ; Ribosomes/physiology* ; Protein Biosynthesis/physiology* ; Mice ; Cardiomyopathy, Dilated/genetics* ; Ribosome Profiling

Sophorae Flavescentis Radix is one of the commonly used traditional Chinese medicine in China, and a large amount of pharmaceutical residue generated during its processing and production is discarded as waste, which not only wastes resources but also pollutes the environment. Therefore, elucidating the chemical composition of the residue of Sophorae Flavescentis Radix and the differences between the residue and Sophorae Flavescentis Radix itself is of great significance for the comprehensive utilization of the residue. This study, based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) technology combined with multivariate statistical methods, provides a thorough characterization, identification, and differential analysis of the overall components of Sophorae Flavescentis Radix and its residue. Firstly, 61 compounds in Sophorae Flavescentis Radix were rapidly identified based on their precise molecular weight, fragment ions, and compound abundance, using a self-constructed compound database. Among them, 41 compounds were found in the residue, mainly alkaloids and flavonoids. Secondly, through principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA), 15 key compounds differentiating Sophorae Flavescentis Radix from its residue were identified. These included highly polar alkaloids, such as oxymatrine and oxysophocarpine, which showed significantly reduced content in the residue, and less polar flavonoids, such as kurarinone and kuraridin, which were more abundant in the residue. In summary, this paper clarifies the overall composition, structure, and content differences between Sophorae Flavescentis Radix and its residue, suggesting that the residue of Sophorae Flavescentis Radix can be used as a raw material for the extraction of its high-activity components, with promising potential for development and application in cosmetics and daily care. This research provides a scientific basis for the future comprehensive utilization of Sophorae Flavescentis Radix and its residue.
Drugs, Chinese Herbal/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Mass Spectrometry/methods* ; Sophora/chemistry* ; Flavonoids/chemistry* ; Alkaloids/chemistry*

This study aims to investigate the protective effects and mechanisms of polysaccharide extract PCP1 from Polygonatum cyrtonema in ameliorating cerebral ischemia-reperfusion(I/R) injury in rats through modulation of the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. In vivo, SD rats were randomly divided into the sham group, model group, PCP1 group, nimodipine(NMDP) group, and TLR4 signaling inhibitor(TAK-242) group. A middle cerebral artery occlusion/reperfusion(MCAO/R) model was established, and neurological deficit scores and infarct size were evaluated 24 hours after reperfusion. Hematoxylin-eosin(HE) and Nissl staining were used to observe pathological changes in ischemic brain tissue. Transmission electron microscopy(TEM) assessed ultrastructural damage in cortical neurons. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and nitric oxide(NO) in serum. Immunofluorescence was used to analyze the expression of TLR4 and NLRP3 proteins. In vitro, a BV2 microglial cell oxygen-glucose deprivation/reperfusion(OGD/R) model was established, and cells were divided into the control, OGD/R, PCP1, TAK-242, and PCP1 + TLR4 activator lipopolysaccharide(LPS) groups. The CCK-8 assay evaluated BV2 cell viability, and ELISA determined NO release. Western blot was used to analyze the expression of TLR4, NLRP3, and downstream pathway-related proteins. The results indicated that, compared with the model group, PCP1 significantly reduced neurological deficit scores, infarct size, ischemic tissue pathology, cortical cell damage, and the levels of inflammatory factors IL-1β, IL-6, IL-18, TNF-α, and NO(P<0.01). It also elevated IL-10 levels(P<0.01) and decreased the expression of TLR4 and NLRP3 proteins(P<0.05, P<0.01). Moreover, in vitro results showed that, compared with the OGD/R group, PCP1 significantly improved BV2 cell viability(P<0.05, P<0.01), reduced cell NO levels induced by OGD/R(P<0.01), and inhibited the expression of TLR4-related inflammatory pathway proteins, including TLR4, myeloid differentiation factor 88(MyD88), tumor necrosis factor receptor-associated factor 6(TRAF6), phosphorylated nuclear factor-kappaB dimer RelA(p-p65)/nuclear factor-kappaB dimer RelA(p65), NLRP3, cleaved-caspase-1, apoptosis-associated speck-like protein(ASC), GSDMD-N, IL-1β, and IL-18(P<0.05, P<0.01). The protective effects of PCP1 were reversed by LPS stimulation. In conclusion, PCP1 ameliorates cerebral I/R injury by modulating the TLR4/NLRP3 signaling pathway, exerting anti-inflammatory and anti-pyroptotic effects.
Animals ; Toll-Like Receptor 4/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Rats, Sprague-Dawley ; Rats ; Reperfusion Injury/genetics* ; Male ; Signal Transduction/drug effects* ; Polysaccharides/isolation & purification* ; Polygonatum/chemistry* ; Brain Ischemia/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Humans

Abuse of amphetamine-based stimulants is a primary public health concern. Recent studies have underscored a troubling escalation in the inappropriate use of prescription amphetamine-based stimulants. However, the neurophysiological mechanisms underlying the impact of acute methamphetamine exposure (AME) on sleep homeostasis remain to be explored. This study employed non-human primates and electroencephalogram (EEG) sleep staging to evaluate the influence of AME on neural oscillations. The primary focus was on alterations in spindles, delta oscillations, and slow oscillations (SOs) and their interactions as conduits through which AME influences sleep stability. AME predominantly diminishes sleep-spindle waves in the non-rapid eye movement 2 (NREM2) stage, and impacts SOs and delta waves differentially. Furthermore, the competitive relationships between SO/delta waves nesting with sleep spindles were selectively strengthened by methamphetamine. Complexity analysis also revealed that the SO-nested spindles had lost their ability to maintain sleep depth and stability. In summary, this finding could be one of the intrinsic electrophysiological mechanisms by which AME disrupted sleep homeostasis.
Animals ; Methamphetamine ; Electroencephalography ; Male ; Sleep/drug effects* ; Central Nervous System Stimulants ; Delta Rhythm/drug effects* ; Sleep Stages/drug effects*

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

ObjectiveTo explore the current situation of forensic ethics practice and education by designing a questionnaire on forensic ethics， with a view to exploring the path of forensic ethics education construction. MethodsA total of 667 valid questionnaires were collected using the online survey method， basically covering various regions across the country and all sub-specialties of forensic medicine. Descriptive analysis was used to analyze the relevant data. ResultsMost practitioners had relevant ethical reflections in the process of forensic practice. 69.12% of the respondents indicated that they had studied the relevant rules， but approximately half stated that there were no corresponding ethical norms or standard operating manuals. The specific behaviors violating ethics in different units were diverse. 23.04% of the respondents reported that they had encountered unethical behaviors， but only 4.9% of them reported such violations. In terms of forensic ethics education， 87.75% of the respondents believed that there were issues with the current model of forensic ethics education. Meanwhile， the respondents showed a high degree of recognition for receiving forensic ethics education， with 84.15% of respondents expressing willingness to participate in relevant courses. More than half of respondents were willing to participate in forensic ethics education during undergraduate studies， new employee training， and regular post-employment training. ConclusionCurrently， there is a problem of ethical neglect in forensic work in China. Combining ethics courses with professional courses at the practitioner training stage and providing regular training at the practice stage are effective measures to popularize forensic ethics knowledge， enhance ethical awareness， and improve the quality of practice.

Objective To explore the relationship between the severity of white matter hyperintensities(WMH)and the distribution of collateral disease syndrome types.Methods A total of 208 patients clearly diagnosed with cerebral small vessel disease in Lishui TCM Hospital Affiliated to Zhejiang Chinese Medical University from December 2022 to December 2023 were selected as the study subjects.All enrolled subjects in the study completed the collateral disease syndrome differentiation.WMH was graded on magnetic resonance imaging fluid-attenuated inversion recovery(FLAIR)sequences using the Fazekas scale and measured for volume.Results Among the 208 patients,there were 52 cases of the brain collateral impoverishment(BCI)type,with Fazekas score of 3(2,3)points,and WMH volume of(8.80±9.37)ml;67 cases of the brain collateral stasis(BCS)type,with Fazekas score of 4(3,4)points,and WMH volume of(13.42±9.18)ml;47 cases of the brain collateral constraint(BCC)type,with Fazekas score of 4(3,5)points,and WMH volume of(14.60±10.07)ml;and 42 cases of the brain collateral occlusion(BCO)type,with Fazekas score of 4(4,5)points,and WMH volume of(18.65±10.71)ml.Of these,55 patients with a Fazekas score of 1-2 points were most commonly of the BCI type,105 patients with a Fazekas score of 3-4 points were most commonly of the BCS type,and 48 patients with a Fazekas score of 5-6 points were most commonly of the BCO type.There were statistically significant differences in Fazekas scores and WMH volumes between the BCI and BCO types and other syndrome types(P＜0.05).Conclusion The severity of WMH corresponds to a certain distribution of collateral disease syndrome types,and can serve as a reference indicator for assessing the severity of illness in patients with collateral disease.

Objective To investigate the clinical efficacy of recombinant human granulocyte-macrophage colony-stimulating factor(rhGM-CSF)combined with bifidobacterium in the treatment of oral mucositis after chemotherapy.Methods A total of 60 post-chemotherapy patients with oral mucositis admitted to Ganzhou Cancer Hospital of Jiangxi Province from January 2023 to December 2024 were selected as subjects,the patients were divided into observation group(n=30)and control group(n=30)by using a randomized digital table method.The control group received rhGM-CSF mouthwash treatment,while the observation group was additionally administered bifidobacterium-lactobacillus triple live capsules orally.Clinical efficacy,symptom scores,inflammatory factor levels,oral microbiota indicators,and treatment safety were evaluated after 2 weeks of treatment.Results After treatment,the total effective rate in observation group was significantly higher than that in control group(P＜0.05).Post-treatment evaluations showed that patients in observation group exhibited lower scores for edema,congestion,and ulceration,along with reduced pain visual analog scores and decreased levels of inflammatory markers including Toll-like receptor 4,lectin-3,and interleukin-8,the difference were statistically significant(P＜0.05).After treatment,the oral microecological flora of patients in observation group,including lactic acid bacteria and bifidobacterium,were higher than that of control group,while porphyromonas gingivalis and fusetella were lower than that of control group,the difference were statistically significant(P＜0.05).Conclusion The clinical effect of rhGM-CSF combined with bifidobacterium in the treatment of oral mucositis after chemotherapy was significant,which could reduce various symptoms of patients,inhibit inflammatory factors,improve oral microecology,and have good safety.

Objective To explore the short-term and long-term efficacy of partial splenic artery embolization(PSE)in the treat-ment of cirrhosis with hypersplenism.Methods A retrospective analysis was conducted on 35 patients with cirrhosis and hyper-splenism who underwent PSE treatment.Data on white blood cell(WBC),red blood cell(RBC),platelet count(PLT),hemoglobin(HGB),total bilirubin(TBiL),albumin(ALB),prothrombin time(PT),and D-dimer were collected at the three time points:before surgery,1 week after surgery,and 1 year after surgery.The changes in these parameters across the three time points were observed and compared.One-way ANOVA was used for repeated measurements,and time pairwise comparisons were made between the three time points.According to the formation of portal thrombosis,patients were divided into thrombus group and no-thrombus group.The D-dimer values were compared before surgery and 1 week after surgery.Results WBC and PLT were significantly higher 1 week and 1 year after surgery than those before surgery,with the most significant increase 1 week after surgery,and there was also statistically sig-nificant difference between 1 week after surgery and 1 year after surgery(P1,P2,P3<0.05).There were no significant differences in RBC and HGB between 1 week after surgery and before surgery(RBC P1=0.835,HGB P1=0.446).However,RBC and HGB 1 year after surgery were significantly higher than those before surgery and 1 week after surgery(RBC P2=0.039,P3=0.015;HGB P2=0.001,P3=0.010).There were significant differences in TBiL,ALB,PT,and D-dimer 1 week after surgery compared with those before surgery(TBiL P1=0.006,ALB P1<0.001,PT P1=0.001,D-dimer P1<0.001),but there was no significant differ-ence between 1 year after surgery and before surgery(all P2>0.05).The D-dimer of the thrombus group was significantly higher than that of the no-thrombus group 1 week after surgery,with a statistical significance(P=0.024),however,there was no signifi-cant difference in D-dimer between the two groups before surgery.Conclusion PSE in the treatment of cirrhosis with hypersplenism shows positive short-term and long-term efficacy for WBC and PLT.The short-term increase of RBC and HGB is not obvious,however the long-term efficacy is significant.In the short-term after surgery,TBiL increase,ALB decrease,PT prolonge,and liver reserve function decrease,but there was no long-term effect.The increase of D-dimer after surgery can easily induce portal thrombosis,and anticoagulation therapy can be given in the short-term after surgery.

Objective To investigate the risk factors of overt hepatic encephalopathy(OHE)and death in cirrhotic portal hyperten-sion patients after transjugular intrahepatic portosystemic shunt(TIPS).Methods A retrospective selection was conducted on 40 patients with cirrhotic portal hypertension who underwent TIPS.The follow-up time was 3-41 months,median follow-up time was 20.36 months.The postoperative hepatic encephalopathy(HE)were divided into OHE group(20 cases)and non-OHE group(20 cases)and were further divided into death group(11 cases)and survival group(29 cases)according to their postoperative survival status.Gender,age,preoperative height,weight,total bilirubin,albumin,alanine aminotransferase,aspartate aminotransferase,creatinine,international normalized ratio(INR),prothrombin time,blood glucose,white blood cells,hemoglobin and platelet of all patients were recorded in detail,as well as whether they had diabetes and portal thrombosis before surgery.Child score and model for end-stage liver disease(MELD)score were also performed.The related risk factors of HE and death were obtained by statistical analysis of the two groups.Results The incidence rate of OHE after TIPS was 50%.The analysis revealed that age[hazard ratio(HR)1.115,95%confidence interval(CI)1.007-1.234,P=0.036]and albumin(HR 0.776,95%CI 0.627-0.960,P=0.020)were independent risk factors for OHE after TIPS.The receiver operating characteristic(ROC)curves were drawn with area under the curve(AUC)of 0.733 for age and AUC of 0.784 for albumin.The mortality rate after TIPS was 27.5%,and the analysis indicated that albumin(HR 0.660,95%CI 0.453-0.961,P=0.030),creatinine(HR 1.031,95%CI 1.001-1.062,P=0.044),and aspartate aminotransferase(HR 1.074,95%CI 1.013-1.139,P=0.018)were independent risk factors for death after TIPS.The ROC curves were drawn with AUC of 0.716 for albumin,AUC of 0.762 for creatinine,and AUC of 0.710 for aspartate aminotransferase.Conclusion Postoperative OHE is posi-tively correlated with age and negatively correlated with albumin.Furthermore,the risk of postoperative death is positively correlated with creatinine and aspartate aminotransferase and negatively correlated with albumin.