Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER ^T2 /Parkin ^fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.

Objective To investigate the impacts of ultrasound-guided stellate ganglion block(SGB)on hemodynamics and postoperative cognitive function in patients undergoing shoulder arthroscopic surgery.Methods From January 2024 to June 2024,120 patients undergoing shoulder arthroscopic surgery in our hospital were randomly assigned into general anesthesia group(n=60,implementing general anesthesia)and assisted SGB group(n=60,implementing ultrasound-guided SGB combined with general anesthesia).The intraoperative hemodynamics,postoperative stress status[serum cortisol(Cor)and interleukin-6(IL-6)],postoperative pain level[evaluated by visual analogue scale(VAS)score],postoperative biomarkers[serum matrix metalloproteinase-9(MMP-9)and neurospecific protein S-100β(S-100β)],and postoperative cognitive function[evaluated using the mini-mental state examination(MMSE)]were compared between the two groups.Results There was no statistically significant difference in intraoperative blood loss and surgical time between the two groups of patients(P>0.05).After induction of anesthesia(T1),the mean arterial pressure(MAP)and heart rate(HR)of the two groups of patients were significantly lower than when they entered the operating room(T0),the differences were statistically significant(P<0.05).The MAP and HR during the beginning of the surgery(T2),30 min after the start of the surgery(T3),and at the end of the surgery(T4)were higher than those at T0,the differences were statistically significant(P<0.05).While the MAP and HR in the assisted SGB group during T1,T2,T3 and T4 time points were lower than those in the general anesthesia group,the differences were statistically significant(P<0.05).The VAS scores of the assisted SGB group were significantly lower than those of the general anesthesia group at 12 and 24 h after surgery,and the differences were statistically significant(P<0.05).The levels of serum Cor and IL-6 in the two groups at 12 and 24 h after surgery were higher than those at 1 d before surgery,but the levels of serum Cor and IL-6 in the assisted SGB group were lower than those in the general anesthesia group,the differences were statistically significant(P<0.05).The levels of serum MMP-9 and S-100β in the two groups at 24 and 72 h after surgery were higher than those at 1 d before surgery(P<0.05),but the levels of serum MMP-9 and S-100β in the assisted SGB group were lower than those in the general anesthesia group,the differences were statistically significant(P<0.05).The MMSE score of the two groups at 3 and 5 d after surgery were lower than those at 1 d before surgery,but the MMSE score of the assisted SGB group was higher than that of the general anesthesia group,the difference was statistically significant(P<0.05).Conclusion The implementation of ultrasound-guided SGB during shoulder arthroscopic surgery can maintain intraoperative hemodynamic stability,obviously alleviate postoperative stress and pain,obviously reduce serum MMP-9 and serum S-100β levels,and help alleviate postoperative cognitive dysfunction.It is worthy clinical application.

Objective To investigate alterations in plasma complement levels and white matter imaging characteristics,along with their relationship in patients with first-episode schizophrenia(SCZ).Methods Thirty-eight patients with first-episode schizophrenia and 42 healthy controls were enrolled.Whole-brain diffusion tensor imaging(DTI)was performed using a Philips 3.0 T MRI scanner.Tract-based spatial statistics(TBSS)combined with the Johns Hopkins University(JHU)white matter labels atlas was used to extract and compare white matter characteristics between the two groups.Plasma levels of complement components(C1q,C3,C4,factor B,factor H,and factor P)were measured using the MILLIPLEX? human complement assay kit via multiplex analysis.Spearman correlation analysis was conducted to examine the association between plasma complement levels and white matter features.Results The radial diffusivity(RD)of the left fornix/stria terminalis was significantly higher in the patient group compared to the control group[(0.62±0.04)×10-3mm2/s vs.(0.60±0.03)×10-3mm2/s,PFDR=0.048)].Factor H[677.71(551.58,846.21)ng/mL vs.582.76(513.93,729.71)ng/mL,P=0.041]and factor P[71.36(57.30,95.99)ng/mL vs.60.08(46.67,80.03)ng/mL,P=0.011]were both significantly elevated compared to the control group.Moreover,RD values in the left fornix/stria terminalis were negatively correlated with plasma C3 levels in the patient group(r=-0.362,P=0.025).Conclusion Patients with first-episode schizophrenia exhibit white matter microstructural abnormalities in left fornix/stria terminalis,which are significantly associated with plasma complement levels.

Objective To investigate the impacts of ultrasound-guided stellate ganglion block(SGB)on hemodynamics and postoperative cognitive function in patients undergoing shoulder arthroscopic surgery.Methods From January 2024 to June 2024,120 patients undergoing shoulder arthroscopic surgery in our hospital were randomly assigned into general anesthesia group(n=60,implementing general anesthesia)and assisted SGB group(n=60,implementing ultrasound-guided SGB combined with general anesthesia).The intraoperative hemodynamics,postoperative stress status[serum cortisol(Cor)and interleukin-6(IL-6)],postoperative pain level[evaluated by visual analogue scale(VAS)score],postoperative biomarkers[serum matrix metalloproteinase-9(MMP-9)and neurospecific protein S-100β(S-100β)],and postoperative cognitive function[evaluated using the mini-mental state examination(MMSE)]were compared between the two groups.Results There was no statistically significant difference in intraoperative blood loss and surgical time between the two groups of patients(P>0.05).After induction of anesthesia(T1),the mean arterial pressure(MAP)and heart rate(HR)of the two groups of patients were significantly lower than when they entered the operating room(T0),the differences were statistically significant(P<0.05).The MAP and HR during the beginning of the surgery(T2),30 min after the start of the surgery(T3),and at the end of the surgery(T4)were higher than those at T0,the differences were statistically significant(P<0.05).While the MAP and HR in the assisted SGB group during T1,T2,T3 and T4 time points were lower than those in the general anesthesia group,the differences were statistically significant(P<0.05).The VAS scores of the assisted SGB group were significantly lower than those of the general anesthesia group at 12 and 24 h after surgery,and the differences were statistically significant(P<0.05).The levels of serum Cor and IL-6 in the two groups at 12 and 24 h after surgery were higher than those at 1 d before surgery,but the levels of serum Cor and IL-6 in the assisted SGB group were lower than those in the general anesthesia group,the differences were statistically significant(P<0.05).The levels of serum MMP-9 and S-100β in the two groups at 24 and 72 h after surgery were higher than those at 1 d before surgery(P<0.05),but the levels of serum MMP-9 and S-100β in the assisted SGB group were lower than those in the general anesthesia group,the differences were statistically significant(P<0.05).The MMSE score of the two groups at 3 and 5 d after surgery were lower than those at 1 d before surgery,but the MMSE score of the assisted SGB group was higher than that of the general anesthesia group,the difference was statistically significant(P<0.05).Conclusion The implementation of ultrasound-guided SGB during shoulder arthroscopic surgery can maintain intraoperative hemodynamic stability,obviously alleviate postoperative stress and pain,obviously reduce serum MMP-9 and serum S-100β levels,and help alleviate postoperative cognitive dysfunction.It is worthy clinical application.

Objective To investigate alterations in plasma complement levels and white matter imaging characteristics,along with their relationship in patients with first-episode schizophrenia(SCZ).Methods Thirty-eight patients with first-episode schizophrenia and 42 healthy controls were enrolled.Whole-brain diffusion tensor imaging(DTI)was performed using a Philips 3.0 T MRI scanner.Tract-based spatial statistics(TBSS)combined with the Johns Hopkins University(JHU)white matter labels atlas was used to extract and compare white matter characteristics between the two groups.Plasma levels of complement components(C1q,C3,C4,factor B,factor H,and factor P)were measured using the MILLIPLEX? human complement assay kit via multiplex analysis.Spearman correlation analysis was conducted to examine the association between plasma complement levels and white matter features.Results The radial diffusivity(RD)of the left fornix/stria terminalis was significantly higher in the patient group compared to the control group[(0.62±0.04)×10-3mm2/s vs.(0.60±0.03)×10-3mm2/s,PFDR=0.048)].Factor H[677.71(551.58,846.21)ng/mL vs.582.76(513.93,729.71)ng/mL,P=0.041]and factor P[71.36(57.30,95.99)ng/mL vs.60.08(46.67,80.03)ng/mL,P=0.011]were both significantly elevated compared to the control group.Moreover,RD values in the left fornix/stria terminalis were negatively correlated with plasma C3 levels in the patient group(r=-0.362,P=0.025).Conclusion Patients with first-episode schizophrenia exhibit white matter microstructural abnormalities in left fornix/stria terminalis,which are significantly associated with plasma complement levels.

Objective:To study the feasibility of magnetic resonance imaging(MRI)technique with amide proton transfer(APT)in predicting the prognosis of cerebral stroke.Methods:A total of 71 patients with acute cerebral stroke who admitted to the Nanjing First Hospital,Nanjing Medical University from September 2022 to May 2023 were selected.All of them underwent the test of National Institute of Health Stroke Scale(NIHSS),and received the MRI examination with chemical exchange saturation transfer(CEST).According to the modified Rankin scale(mRS)values of 1-month follow-up,they were divided into favorable recovery group(mRS<2,44 cases)and poor group(mRS≥2,27 cases).The asymmetric magnetization transfer ratio(MTRasym)image(APT)was obtained by analyzing data with special software.And then,the difference(△APTw)of APT values between ischemic zone and contralateral normal tissue was further calculated.The △APTw values of two groups were compared and analyzed,and the Pearson correlation analysis was adopted to analyze the correlation among △APTw,NIHSS and mRS.The receiver operating characteristics(ROC)curve was drawn,and the area under curve(AUC)of ROC curve was calculated.Results:There were significant positive correlations among △APTw,NIHSS and mRS scores(R2=0.659,0.522,P<0.001),and the differences of △APTW,NIHSS and mRS scores between the favorable recovery group and poor group were significant(t=5.73,6.36,13.92,P<0.05),respectively.The AUC value was 0.886,and the sensitivity and specificity of prediction were respectively 77.8%and 95.5%.The positive and negative predictive values were respectively 91.3%and 87.5%.Conclusion:APT imaging technique has feasibility in predicting the prognosis of acute cerebral ischemic stroke.

OBJECTIVE: To investigate the effects of fecal microbiota transplantation (FMT) on intestinal microbiome and organism in patients with severe pneumonia during the convalescence period. METHODS: A prospective non-randomized controlled study was conducted. From December 2021 to May 2022, patients with severe pneumonia during the convalescence period who received FMT (FMT group) and patients with severe pneumonia during the convalescence period who did not receive FMT (non-FMT group) admitted to the First Affiliated Hospital of Guangzhou Medical University were enrolled. The differences of clinical indicators, gastrointestinal function and fecal traits between the two groups were compared 1 day before and 10 days after enrollment. The 16S rDNA gene sequencing technology was used to analyze the changes of intestinal flora diversity and different species in patients with FMT before and after enrollment, and metabolic pathways were analyzed and predicted by Kyoto Encyclopedia of Genes and Genomes database (KEGG). Pearson correlation method was used to analyze the correlation between intestinal flora and clinical indicators in FMT group. RESULTS: The level of triacylglycerol (TG) in FMT group was significantly decreased at 10 days after enrollment compared with before enrollment [mmol/L: 0.94 (0.71, 1.40) vs. 1.47 (0.78, 1.86), P < 0.05]. The level of high-density lipoprotein cholesterol (HDL-C) in non-FMT group was significantly decreased at 10 days after enrollment compared with before enrollment (mmol/L: 0.68±0.27 vs. 0.80±0.31, P < 0.05). There were no significant differences in other clinical indexes, gastrointestinal function or fecal character scores between the two groups. Diversity analysis showed that the α diversity indexes of intestinal flora in FMT group at 10 days after enrollment were significantly higher than those in non-FMT group, and β diversity was also significantly different from that in non-FMT group. Differential species analysis showed that the relative abundance of Proteobacteria at the level of intestinal flora in FMT group at 10 days after enrollment was significantly lower than that in non-FMT group [8.554% (5.977%, 12.159%) vs. 19.285% (8.054%, 33.207%), P < 0.05], while the relative abundance of Fusobacteria was significantly higher than that in non-FMT group [6.801% (1.373%, 20.586%) vs. 0.003% (0%, 9.324%), P < 0.05], and the relative abundance of Butyricimonas, Fusobacterium and Bifidobacterium at the genus level of the intestinal flora was significantly higher than that in non-FMT group [Butyricimonas: 1.634% (0.813%, 2.387%) vs. 0% (0%, 0.061%), Fusobacterium: 6.801% (1.373%, 20.586%) vs. 0.002% (0%, 9.324%), Bifidobacterium: 0.037% (0%, 0.153%) vs. 0% (0%, 0%), all P < 0.05]. KEGG metabolic pathway analysis showed that the intestinal flora of FMT group was changed in bisphenol degradation, mineral absorption, phosphonate and phosphinate metabolism, cardiac muscle contraction, Parkinson disease and other metabolic pathways and diseases. Correlation analysis showed that Actinobacteria and prealbumin (PA) in intestinal flora of FMT group were significantly positively correlated (r = 0.53, P = 0.043), Bacteroidetes was positively correlated with blood urea nitrogen (BUN; r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Firmicutes was positively correlated with BUN (r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Fusobacteria was significantly positively correlated with immunoglobulin M (IgM; r = 0.71, P = 0.003), Proteobacteria was significantly positively correlated with procalcitonin (PCT; r = 0.63, P = 0.012) and complement C4 (r = 0.56, P = 0.030). CONCLUSIONS FMT can reduce TG level, reconstruct intestinal microecological structure, change body metabolism and function, and alleviate inflammatory response by reducing the relative abundance of harmful bacteria in patients with severe pneumonia during the convalescence period.
Humans ; Fecal Microbiota Transplantation ; Complement C3 ; Convalescence ; Prospective Studies ; Feces

Humans ; Depressive Disorder, Major ; Motor Cortex ; Magnetic Resonance Imaging

Hereditary spastic paraplegia type 58 is rare, caused by pathogenic variations in KIF1C gene. Here, a case diagnosed in Qilu Hospital, Shandong University, was reported. The 15-year-old female suffered tremor in bilateral upper limbs which was aggravated gradually since age 8. Cerebellar ataxia, positive pyramidal tract sign and dystonic tremor were prominent on physical examination. The brain magnetic resonance imaging showed T 2-hyperintense signals in bilateral pyramidal tracts, optic radiations and superior cerebellar peduncles, with mild cerebellar atrophy. Whole exon sequencing revealed the unreported homozygous c.425_426delTG (p.V142Gfs*10) mutation which was presumed pathogenic.

Objective:To explore the effect of artificial intelligence teaching-picture system in training the bone marrow cell morphological reading ability of clinical medical students.Methods:A total of 110 five-year undergraduate students were divided into experimental group (artificial intelligence picture teaching method) and control group (traditional teaching method) in the bone marrow cell morphology reading ability training. On the basis of multimedia teaching, the experimental group was given the teaching by using the bone marrow cell morphology picture storage and transmission system for retrieval, learning and computer adaptive test. Then objective evaluation of image recognition ability and questionnaire were used to compare the teaching effect.Results:The image recognition ability was significantly better in the experimental group than in the control group [(89.6±5.7) vs. (81.4±4.9), P<0.01]. Furthermore, the experimental group showed more obvious advantages in cell morphology recognition [(74.7±4.0) vs. (68.7±4.9)] and diagnosis of hematological diseases [(14.9±3.0) vs. (12.9±2.4)] than the control group (both P<0.01). Questionnaire survey showed that the students expressed their affirmation and support for the artificial intelligence teaching-picture system in the bone marrow cell morphological reading ability training. Conclusion:The application of artificial intelligence teaching-picture system can greatly improve the teaching effect, mobilize students' learning enthusiasm and expand learning resources, which is worthy of further promotion and application.