Taxifolin (TAX) is a natural compound known for its liver protection effect, but the mechanism remains unknown. Phosphorylated proteomics analyses discovered that the phosphorylation level of NDRG1 at T328 was a key event of TAX-improved liver fibrosis. We established models with NDRG1 knockout (KO) in vivo and in vitro, demonstrating that NDRG1 KO attenuated the development of hepatocyte injury, and combining NDRG1 KO and TAX administration did not result in a reduction in protection against liver injury. Cellular thermal shift assay and surface plasma resonance analysis showed that TAX directly binds to NDRG1 rather than its upstream kinase, subsequently demonstrating that TAX regulated phosphorylation of NDRG1 at T328 through binding to its C289 site. NDRG1 T328A (phosphorylated mutation) and T328E (mimic phosphorylation) in vivo and in vitro confirmed that pNDRG1_T328 exacerbates hepatocyte injury along with DNA damage, inflammatory response, and apoptosis, thereby contributing to hepatic stellate cells (HSCs) activation. In contrast, TAX can inhibit the above pathological abnormalities and block hepatocyte injury-triggered HSCs activation and fibrosis. Overall, TAX is a potent liver protection drug primarily targeting NDRG1 and inhibiting pNDRG1_T328 in hepatocytes.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Blonanserin,a second-generation atypical antipsychotic agent,acts as an antagonist for dopamine D2,D3,and serotonin 5-HT2A receptors.Clinical studies have demonstrated that blonanserin is non-inferior to other antipsychotics,such as haloperidol and risperidone,in alleviating the symptoms of schizophrenia.Moreover,it exhib-its beneficial effects on cognitive symptoms and social functioning,with a favorable safety profile,making it one of the key treatment options for schizophrenia.With extensive clinical experience accumulated in China,this expert consensus aims to provide psychiatrists with updated and localized guidance on the optimal use of blonan-serin.Based on a systematic review of the latest evidence-particularly studies in Chinese population,this paper pres-ents the updated Chinese expert recommendations for the clinical use of blonanserin in 2024.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Objective To observe the effect of RAW264.7 cells on calcium sparks in a insulin resistance model of C2C12 cells induced by sodium palmitate.Methods C2C12 cells and RAW264.7 cells were co-cultured to simulate the in vivo state of skeletal muscle.C2C12 cells were cultured in high-glucose medium containing 2%horse serum to induce differentiation into mature myotubes,and then divided into 5 groups:control(RAW264.7 cells),co-culture of C2C12 with RAW264.7,C2C12 alone,co-culture of C2C12 with RAW264.7 plus sodium palmitate(PA),and C2C12 alone with PA.PA of 5 mmol/L was used to induce insulin resistance in C2C12 cells for 24 hours.Revived and expanded RAW264.7 cells were evenly added to C2C12 cells and co-cultured for two days.Subsequently,cells were maintained in modified suspension culture,and both cell types were loaded with the calcium ion fluorescent probe Fluo-4 AM.Finally,Paraxanthine was used to induce intracellular calcium sparks,which was captured and recorded under a laser confocal microscope.Results No significant calcium signal change was observed in the control group.Co-cultured C2C12 cells exhibited rapid and pronounced calcium signal changes,whereas calcium signals in C2C12 cells cultured alone increased slowly throughout the observation period without a sharp decline.The peak calcium signal was reached significantly faster in co-cultured C2C12 cells than that in C2C12 cells cultured alone(P<0.001).With PA induction,calcium signal changes in C2C12 cells were not markedly altered,while distinct calcium fluctuations were still observed in co-cultured C2C12 cells,and the peak calcium signal was reached significantly faster in co-cultured C2C12 cells than that in C2C12 cells cultured alone(P<0.001).Conclusion RAW264.7 cells enhance the dynamic responsiveness of calcium signaling in both normal and PA-stimulated C2C12 cells.

Objective:In alignment with the practical teaching objectives of Diseases of the Locomotor System and the competency requirements for graduates of military medical universities, this study conducted a multidimensional modification of the traditional objective structured clinical examination (OSCE) to provide a novel training mode that enhances the effectiveness of practical teaching of this course.Methods:The traditional OSCE was modified from the four dimensions of integration, individuality, immersion, and intelligence. The first three stations were set as "diagnosis" and the last three stations were set as "operation" to reflect the "integration" of diagnosis and treatment. The last station of "operation" was set as "medical cares of combat and training injuries" to reflect "individuality" of military medical training. The method of situation creation was used to reflect "immersion", and the application of intelligent terminals reflected "intelligence". The study involved 50 trainees who were assigned to either a modified OSCE group or a traditional teaching group through a random drawing process. The teaching effectiveness was assessed through evaluation of theoretical knowledge, practical skills, and participant satisfaction. The statistical analysis was conducted by SPSS 22.0, with parametric data assessed by t-tests and non-parametric data assessed by chi-square tests. Results:Before entering the department, there were no statistically significant differences in theoretical ( P=0.832) and practical ( P=0.513) scores between the two groups of trainees. However, after the internship, the modified OSCE group demonstrated significantly enhanced scores compared to the traditional teaching group, both in theory assessment [(93.88±1.92) vs. (90.76±2.85), P=0.001] and skill assessment [(94.32±1.25) vs. (91.68±2.82), P=0.001]. Additionally, the self-assessment of clinical capability improvement by the modified OSCE group was markedly higher across all dimensions than the traditional teaching group ( P=0.001). Furthermore, the evaluation conducted by basic combat unit on the job competency of graduated trainees indicated that the modified OSCE group outperformed the traditional teaching group in basic clinical diagnosis and treatment [(4.72±0.46) vs. (3.44±0.71), P=0.001], emergency management of combat and training injuries [(4.72±0.46) vs. (3.52±0.71), P=0.001], application of information technology [(4.44±0.71) vs. (3.91±0.80), P=0.029], basic military qualities [(4.40±0.71) vs. (3.92±0.91), P=0.043], mental health and resilience [(4.36±0.70) vs. (3.68±0.85), P=0.003], and the capacity for continuous learning [(4.64±0.70) vs. (3.83±0.76), P=0.001]. Conclusions:The modified OSCE teaching mode can better meet the practical teaching requirements for Diseases of the Locomotor System in the military medical university and thus holds promise for further application.

Objective:To explore the effect of combining intensive laryngeal elevation training with repeated transcranial magnetic stimulation (rTMS) based on the concept of " central-peripheral-central" (CPC) on dysphagia in stroke survivors.Methods:Eighty stroke survivors with dysphagia were selected and randomly divided into a control group, a lift group, an rTMS group and a combination group, each of 20. In addition to neurologic drug therapy and routine swallowing training, the lift group received intensive throat elevation training, the rTMS group received rTMS, while the combination group underwent both before and after 4 weeks of treatment, all were evaluated using video swallowing angiography (VFSS), a leakage-aspiration scale (PAS) and a functional oral feeding scale (FOIS).Results:After the treatment, the average VFSS, PAS and FOIS scores had improved significantly in all 4 groups, with those of the lift group, the rTMS group and the combination group then significantly better than the control group′s averages. The combination group′s scores were significantly better than those of the other 3 groups. There was no significant difference in any of the indexes between the lift and TMS groups.Conclusions:CPC-based intensive laryngeal ascent training combined with rTMS can significantly improve the swallowing of stroke survivors with dysphagia in convalescence.

Blonanserin,a second-generation atypical antipsychotic agent,acts as an antagonist for dopamine D2,D3,and serotonin 5-HT2A receptors.Clinical studies have demonstrated that blonanserin is non-inferior to other antipsychotics,such as haloperidol and risperidone,in alleviating the symptoms of schizophrenia.Moreover,it exhib-its beneficial effects on cognitive symptoms and social functioning,with a favorable safety profile,making it one of the key treatment options for schizophrenia.With extensive clinical experience accumulated in China,this expert consensus aims to provide psychiatrists with updated and localized guidance on the optimal use of blonan-serin.Based on a systematic review of the latest evidence-particularly studies in Chinese population,this paper pres-ents the updated Chinese expert recommendations for the clinical use of blonanserin in 2024.

Objective:To explore the effect of combining intensive laryngeal elevation training with repeated transcranial magnetic stimulation (rTMS) based on the concept of " central-peripheral-central" (CPC) on dysphagia in stroke survivors.Methods:Eighty stroke survivors with dysphagia were selected and randomly divided into a control group, a lift group, an rTMS group and a combination group, each of 20. In addition to neurologic drug therapy and routine swallowing training, the lift group received intensive throat elevation training, the rTMS group received rTMS, while the combination group underwent both before and after 4 weeks of treatment, all were evaluated using video swallowing angiography (VFSS), a leakage-aspiration scale (PAS) and a functional oral feeding scale (FOIS).Results:After the treatment, the average VFSS, PAS and FOIS scores had improved significantly in all 4 groups, with those of the lift group, the rTMS group and the combination group then significantly better than the control group′s averages. The combination group′s scores were significantly better than those of the other 3 groups. There was no significant difference in any of the indexes between the lift and TMS groups.Conclusions:CPC-based intensive laryngeal ascent training combined with rTMS can significantly improve the swallowing of stroke survivors with dysphagia in convalescence.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.