The study aims to examine the effects and potential mechanisms of disulfiram (DSF) on cardiac hypertrophic injury, focusing on the role of transforming growth factor-β-activated kinase 1 (TAK1)-mediated pan-apoptosis (PANoptosis). H9C2 cardiomyocytes were treated with angiotensin II (Ang II, 1 µmol/L) to establish an in vitro model of myocardial hypertrophy. DSF (40 µmol/L) was used to treat cardiomyocyte hypertrophic injury models, either along or in combination with the TAK1 inhibitor, 5z-7-oxozeaenol (5z-7, 0.1 µmol/L). We assessed cell damage using propidium iodide (PI) staining, measured cell viability with CCK8 assay, quantified inflammatory factor levels in cell culture media via ELISA, detected TAK1 and RIPK1 binding rates using immunoprecipitation, and analyzed the protein expression levels of key proteins in the TAK1-mediated PANoptosis pathway using Western blot. In addition, the surface area of cardiomyocytes was measured with Phalloidin staining. The results showed that Ang II significantly reduced the cellular viability of H9C2 cardiomyocytes and the binding rate of TAK1 and RIPK1, significantly increased the surface area of H9C2 cardiomyocytes, PI staining positive rate, levels of inflammatory factors [interleukin-1β (IL-1β), IL-18, and tumor necrosis factor α (TNF-α)] in cell culture media and p-TAK1/TAK1 ratio, and significantly up-regulated key proteins in the PANoptosis pathway [pyroptosis-related proteins NLRP3, Caspase-1 (p20), and GSDMD-N (p30), apoptosis-related proteins Caspase-3 (p17), Caspase-7 (p20), and Caspase-8 (p18), as well as necroptosis-related proteins p-MLKL, RIPK1, and RIPK3]. DSF significantly reversed the above changes induced by Ang II. Both 5z-7 and exogenous IL-1β weakened these cardioprotective effects of DSF. These results suggest that DSF may alleviate cardiac hypertrophic injury by inhibiting TAK1-mediated PANoptosis.
Animals ; MAP Kinase Kinase Kinases/physiology* ; Rats ; Myocytes, Cardiac/pathology* ; Disulfiram/pharmacology* ; Cardiomegaly ; Apoptosis/drug effects* ; Cell Line ; Angiotensin II ; Necroptosis/drug effects* ; Interleukin-1beta/metabolism* ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Lactones ; Resorcinols ; Zearalenone/administration & dosage*

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Objective To observe the effects of"Sleep Recipe"on the behavior,brain tissue and central neurotransmitters of insomnia rats.Methods The male rats with SD were randomly divided into control group,model group,sleep formula group,and eszolam group,with 10 rats in each group,and the insomnia model was constructed by intraperitoneal injection of P-chlorphenylalanine(PCPA).After successful modeling,the control group and the model group were given saline gavage,and the medylom group and eszolam group were given drug gavage.The insomnia-like behavior of rats in each group was evaluated by pentobarbital sodium correction experiment and open field experiment,Hematoxlin and eosin(HE)staining observed the pathological changes of rat cerebral cortex,hippocampus,and hypothalamic tissue,and Enzyme-linked mmunosorbent assay(ELISA)was used to determine the expression levels of Gamma-aminobutyric acid(GABA),5-hydroxytryptamine(5-HT).Results The sleep latency of rats in the model group was significantly elongated(P<0.01),while the sleep time was less(P<0.01),and the mental state and fur color were poor,significantly decreased in body weight(P<0.01).Compared with the model group,the sleep latency was significantly shortened(P<0.01),the sleep duration was significantly prolonged(P<0.01),and the body mass was significantly increased(P<0.05,P<0.01);In the open field experiment,the total activity distance of rats in the model group increased,the average speed and central region residence time decreased(P<0.05),the total activity distance of rats in the Sleep Formula group and Eszolam group decreased significantly(P<0.05),the average speed increased and the central region residence time increased(P<0.05).HE results showed that the number of neurons,morphological structure and arrangement of neurons,such as cerebral cortex,hippocampus and hypothalamus in the model group,were damaged to varying degrees,and the sleep formula group and estazolam group were significantly improved.ELISA results showed that the expression of 5-HT and GABA in the cerebral cortex and hypothalamus of rats in the model group was significantly reduced(P<0.01,P<0.05),and the expression of GABA in hippocampal tissues was also significantly reduced(P<0.01).The protein expression levels of cerebral cortical GABA,hypothalamic GABA and 5-HT in the Sleep Formula group were significantly increased(P<0.01).Conclusion Sleep Formula can improve the mental state,restore normal body weight,improve sleep efficiency,and reduce anxiety and tension in insomnia rats.The mechanism may be related to increasing the content of 5-HT and GABA,and inhibiting the spread and conduction of hypothalamic and brainstem pro-awakening nuclei.

Objective:To evaluate the efficiency of the four domestic language models,ERNIE Bot,ChatGLM2,Spark Desk and Qwen-14B-Chat,all with a massive user base and significant social attention,in response to consultations about PCa-related perio-perative nursing and health education.Methods:We designed a questionnaire that includes 15 questions commonly concerned by patients undergoing radical prostatectomy and 2 common nursing cases,and inputted the questions into each of the four language models for simulation consultation.Three nursing experts assessed the model responses based on a pre-designed Likert 5-point scale in terms of accuracy,comprehensiveness,understandability,humanistic care,and case analysis.We evaluated and compared the performance of the four models using visualization tools and statistical analyses.Results:All the models generated high-quality texts with no mis-leading information and exhibited satisfactory performance.Qwen-14B-Chat scored the highest in all aspects and showed relatively sta-ble outputs in multiple tests compared with ChatGLM2.Spark Desk performed well in terms of understandability but lacked comprehen-siveness and humanistic care.Both Qwen-14B-Chat and ChatGLM2 demonstrated excellent performance in case analysis.The overall performance of ERNIE Bot was slightly inferior.All things considered,Qwen-14B-Chat was superior to the other three models in con-sultations about PCa-related perioperative nursing and health education.Conclusion:In PCa-related perioperative nursing,large language models represented by Qwen-14B-Chat are expected to become powerful auxiliary tools to provide patients with more medical expertise and information support,so as to improve the patient compliance and the quality of clinical treatment and nursing.

As the research of traditional Chinese medicine （TCM） on knee osteoarthritis （KOA） is progressing， researchers have discovered that a variety of Chinese medicines can delay the progress of KOA by regulating signaling pathways at the molecular level. The Chinese medicines and their active ingredients mentioned in this article are associated with the signaling pathways in KOA. They can regulate the levels of targeted molecules via different signaling pathways to inhibit cartilage inflammatory cytokine， apoptosis， and cartilage matrix degradation and promote chondrocyte autophagy， so as to reduce the synovial inflammatory edema and delay cartilage degeneration. This paper systematically reviews the studies about the TCM intervention of KOA. Baicalein can reduce the inflammatory cytokines and apoptosis and promote the autophagy of chondrocytes by blocking the phosphatidylinositol-3 kinase/protein kinase （PI3K/Akt） signaling pathway. Cornuside I can decrease the phosphorylation activity of Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） pathway to reduce synovial inflammation and delay cartilage matrix degeneration. Salvianolic acid A can reduce inflammation and cartilage matrix degradation by inhibiting the phosphorylation of the nuclear factor-κB （NF-κB） pathway. Emodin can reduce the activity of Wnt/β-catenin pathway to inhibit the decomposition of collagen and proteoglycan. Myristicoside can inhibit apoptosis by blocking the p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. Akebia saponin D can enhance the activity of nuclear factor E₂-related factor 2/heme oxygenase 1（Nrf2/HO-1） pathway to inhibit oxidative stress in chondrocytes. The saponins in Achyranthis Bidentatae Radix reduce cartilage matrix degradation by enhancing the transforming growth factor-β （TGF-β）/Smad signaling pathway. Crocin inhibits the cartilage inflammation and apoptosis factor increase by stimulating the activity of hippo-Yes-associated protein （Hippo-YAP）. Ligustrazine blocks the Notch pathway to improve the morphology and abnormality of chondrocytes. Oleanolic acid reduces the destruction and degeneration of cartilage matrix via the estrogen signaling pathway. The above summary aims to provide references for future clinical and experimental research on KOA.

Humans ; SARS-CoV-2 ; COVID-19

Objective: To investigate the etiology, complications, and prognostic factors of stage 5 chronic kidney disease (CKD5) in children. Methods: A case series study was conducted to retrospectively analyze the general situation, clinical manifestations, laboratory tests, genetic testing, and follow-up data (until October 2022) of 174 children with CKD5 who were diagnosed and hospitalized at the Children's Hospital of Chongqing Medical University from April 2012 to April 2021. The characteristics of complications in the children were compared based on age, gender, and etiology. Based on the presence or absence of left ventricular hypertrophy (LVH), patients were divided into LVH group and non LVH group for analyzing the influencing factors of cardiovascular disease. Patients were also divided into death group and survival group, peritoneal dialysis group and hemodialysis group based on the follow-up data for analyzing the prognostic factors. The chi-square test, independent sample t-test, Fisher exact probability test, Mann-Whitney U test and Kruskal Wallis test were used to analyze data among different groups. Multivariate Logistic regression analysis was used to identify the prognostic factors. Results: A total of 174 children with CKD5 were enrolled in the study (96 boys and 78 girls), aged 11.2 (8.2, 13.0) years. Congenital kidney and urinary tract malformations (CAKUT) were the most common causes of the CKD5 (84 cases, 48.3%), followed by glomerular diseases (83 cases, 47.7%), and among which 28 cases (16.1%) were hereditary glomerular diseases. The common complications of CKD5 included anemia (98.2%, 165/168), mineral and bone disorder in chronic kidney disease (CKD-MBD) (97.7%, 170/174), lipid metabolism disorders (87.5%, 63/72), hypertension (81.4%, 127/156) and LVH (57.6%,57/99). The incidences of hypertension in primary glomerular disease were higher than that in CAKUT(93.8%(30/32) vs.73.7%(56/76),χ²=5.59,P<0.05). The incidences of hypertension in secondary glomerular disease were higher than that in CAKUT and that in hereditary kidney disease (100.0%(20/20) vs. 73.7%(56/76), 68.2%(15/22), both P<0.05). The incidence of hypocalcemia in CAKUT, primary glomerular disease, and hereditary kidney disease was higher than that in secondary glomerular disease (82.1%(69/84), 88.2%(30/34), 89.3%(25/28) vs. 47.6%(10/21), χ²=10.21, 10.75, 10.80, all P=0.001); the incidence of secondary hyperparathyroidism in women was higher than that in men (80.0%(64/80) vs. 95.0%(57/60), χ²=6.58, P=0.010). The incidence of LVH in children aged 6-<12 was higher than that in children aged 12-18 (73.5%(25/34) vs. 43.1%(22/51), χ²=7.62, P=0.006). Among 113 follow-up children, the mortality rate was 39.8% (45/113). Compared to the survival group, the children in the death group had lower hemoglobin, higher blood pressure, lower albumin, lower alkaline phosphatase and higher left ventricular mass index ((67±19) vs. (75±20) g/L, 142 (126, 154) vs. 128(113, 145) mmHg(1 mmHg=0.133 kPa), (91±21) vs. (82±22) mmHg, 32 (26, 41) vs. 40 (31, 43) g/L, 151 (82, 214) vs. 215 (129, 37) U/L, 48 (38, 66) vs. 38(32, 50) g/m^2.7,t=2.03, Z=2.89, t=2.70, Z=2.49, 2.79, 2.29,all P<0.05), but no independent risk factors were identified (all P>0.05). The peritoneal dialysis group had better alleviation for anemia, low calcium, and high phosphorus than the hemodialysis group ((87±22) vs. (72±16) g/L, (1.9±0.5) vs. (1.7±0.4) mmol/L, (2.2±0.7) vs. (2.8±0.9) mmol/L, t=2.92, 2.29, 2.82, all P<0.05), and the survival rate of the peritoneal dialysis group was significantly higher than that of the hemodialysis group (77.8% (28/36) vs. 48.4% (30/62), χ²=8.14, P=0.004). Conclusions: CAKUT is the most common etiology in children with CKD 5, and anemia is the most common complication. The incidence of complications in children with CKD 5 varies with age, gender and etiology. Anemia, hypertension, hypoalbuminemia, reduced alkaline phosphatase and elevated LVMI may be the prognostic factors in children with CKD5. Peritoneal dialysis may be more beneficial for improving the long-term survival rate.
Male ; Humans ; Child ; Female ; Retrospective Studies ; Alkaline Phosphatase ; Kidney Failure, Chronic/therapy* ; Renal Insufficiency, Chronic/therapy* ; Hypertension ; Risk Factors ; Hypertrophy, Left Ventricular/etiology* ; Anemia/etiology*

Carboxyl CoA ligases(CCLs) is an important branch of adenylate synthetase gene family, which mainly has two-step catalytic reactions. Firstly, in the presence of adenosine triphosphate, it can catalyze the pyrophosphorylation of carboxylateswith diffe-rent structures to form corresponding acyl adenosine monophosphate intermediates. Secondly, adenosine monophosphate was replaced by free electrons in the mercaptan group of enzyme A or other acyl receptors by nucleophilic attack to form thioesters. In this study, on the basis of the transcriptome database of Arnebia euchroma, two genes were selected, named AeCCL5(XP_019237476.1) and AeCCL7(XP_019237476.1). Bioinformatics analysis showed that their relative molecular weights were 60.569 kDa and 60.928 kDa, theoretical PI were 8.59 and 8.92, respectively. They both have transmembrane domains but without signal peptide. By multiple sequence alignment and phylogenetic tree analysis, we found that the similarity between AeCCLs and other plant homologous proteins was not high, and the substrate binding sites of AeCCLs were not highly conserved. The reasons might be that the sequence and structure need to adapt to the changes of new substrates in the process of evolution. In this study, the full-length of AeCCL5 and AecCCL7 were cloned into the expression vector pCDFDuet-1. The proteins of AeCCL5 and AeCCL7 with His-tag were expressed in Escherichia coli. The proteins of AeCCL5 and AeCCL7 were purified by nickel column. In vitro enzymatic reactions proved that both AeCCL5 and AeCCL7 can participate in the upstream phenylpropane pathway of shikonin biosynthesisby catalyzing 4-coumaric acid to produce 4-coumarin-CoA, and then to synthesis p-hydroxybenzoic acid, which is an important precursor of shikonin biosynthesis in A. euchroma.
Boraginaceae/genetics* ; Cloning, Molecular ; Coenzyme A ; Coenzyme A Ligases/genetics* ; Ligases ; Phylogeny

Objective:To explore the clinical effect of open reduction in the treatment of Tile C pelvic fracture combined with acetabular fracture in a specific sequence.Methods:Retrospectively analyzed the clinical data of 53 patients with Tile C type pelvic fracture combined with acetabular fracture from January 2014 to January 2019, and were divided into specific sequence group and non-specific sequence group according to the sequence of intraoperative reduction. A total of 29 cases were observed in the specific sequence group, including 20 males and 9 females; aged 43.8±14.8 years old (18-71 years), and the fractures were reduced in the sequence of "inside and out, then up and down" during the operation. There were 24 cases in the non-specific sequence group, including 14 males and 10 females; aged 44.4±14.7 years old (18-69 years), and fracture reduction was not performed in this sequence during the operation. According to the type of pelvic and acetabular fracture injury, we choose the appropriate position and surgical approach. After open reduction, the fracture was fixed with internal plants. The intraoperative blood loss, operation time, visual analogue scale (VAS) score were compared between the two groups. The quality of fracture reduction was evaluated by Matta score, pelvic fracture function recovery was evaluated by Majeed score, and acetabular fracture was evaluated by hip joint modified Merle d'Aubigné-Postel score.Results:There was no statistically significant difference in general data between the two groups before operation ( P>0.05), which was comparable. The intraoperative blood loss of the specific sequence group and the non-specific sequence group were 1 031.1±513.7 and 1 406.3±738.1 ml, and the operation time was 3.5±1.0 and 4.8±1.4 h; The differences between the two groups were statistically significant ( P<0.05). 53 patients were followed up for 14.8±1.6 months (12-18 months) after operation. The average postoperative VAS scores of specific sequence group and non-specific sequence group were 1.3±1.1 and 1.5±1.3 respectively, and there was no statistically significant difference. The effectiveness of the pelvic fracture Matta score standard was evaluated in the specific sequence group: excellent in 22 cases, good in 5 cases, fair in 2 cases, excellent and good rate was 93.1%; non-specific sequence group excellent in 10 cases, good in 6 cases, fair in 5 cases, poor in 3 cases, excellent and good rate was 66.7%, the difference was statistically significant ( P<0.05). Matta score of acetabular fracture: 21 cases were excellent in specific sequence group, 5 cases were good, 3 cases were poor, excellent and good rate was 89.7%; 9 cases were excellent in non-specific sequence group, 8 cases were good, 7 cases were poor, excellent and good rate was 70.8 %, the difference is statistically significant ( P<0.05). The results of the last follow-up pelvic fractures were evaluated by Majeed score: 20 cases were excellent in the specific sequence group, 7 were good, 2 were fair, excellent and good rate was 93.1%; 10 were excellent in the non-specific sequence group, 5 were good, 5 were fair, and 4 were poor, excellent and good rate was 62.5%, the difference was statistically significant ( P<0.05). At the last follow-up, the modified Merle d'Aubigné-Postel score was used to evaluate the efficacy: 20 cases were excellent in the specific sequence group, 5 were good, 4 were fair, the excellent and good rate was 86.2%; In the non-specific sequence group, 9 cases were excellent, 7 cases were good, 4 cases were fair, and 4 cases were poor, excellent and good rate was 66.7%, the difference was statistically significant ( P<0.05). During the follow-up period, none of the patients in the two groups developed fracture nonunion, heterotopic ossification, iatrogenic neurovascular injury, and femoral head necrosis. Trauma arthritis occurred in 4 patients in the non-specific sequence group. Conclusion:"Inside and out, then up and down" sequential reduction of Tile C pelvis combined with acetabular fracture can significantly shorten the operation time and reduce the amount of intraoperative blood loss. The surgical procedure is reasonable, which helps to improve the quality of fracture reduction and promote the functional recovery of patients.

Objective To explore the theories, content and approaches of integrating physical activity in children's eye health service system in the context of health services. Methods From the perspectives of six building blocks of WHO health system, namely, leadership and governance, financing, human resources for health, service delivery, medical technology, and health information system, we analyzed the policy framework and key contents related to school-based eye health and physical activity, and explored how to promote the implementation of physical activity into the school-based eye health service system, and the integration of physical activity into the eye health continuum: prevention, intervention, rehabilitation, and health promotion. Results In perspective of health system, the integration of physical activity into school-based eye health services should be in accordance with the five principles of cross-cutting health services, namely, universal accessibility and equity, human rights, evidence-based, life-span, and empowerment. According to the World Vision Report, WHO advocates to build a person-centered eye health service system, and person-centeredness is the core concept of the new model of school-based eye health services and physical activity integration. WHO advocates a school-based approach to education and physical activity in health-promoting schools to promote student health, physical activity as a preventive, interventional, rehabilitation and health promotive measure related to children's eye health, and vigorously train professionals within schools who have knowledge and skills related to physical activity and eye health, build an information system on physical activity and children's eye health, and promote the integration of physical activity into the school-based eye health service system. Conclusion Physical activity is an important measure to promote children's eye health and an important component to achieve a person-centered eye health service system. Based on the six building blocks of the WHO health service system, a school-based eye health service that integrates a theoretical and methodological system of physical activity is constructed, requiring the provision of health promotion methods such as education and physical activity in the school setting, to enhance leadership and governance of eye health services based on educational and physical activity approaches in the school setting, establish new funding mechanisms, provide financial security, develop human resources related to physical activity for eye health, improve related service delivery systems, develop high-quality physical activity intervention eye health techniques and equipment, and integrate information on children's physical activity and eye health into school health information systems to achieve children's eye health and promote their physical and mental development.