Objective To explore the effect of remote ischemic preconditioning (RIPC) on preoperative heart rate variability in patients with heart valves. Methods Patients scheduled to undergo on-pump cardiac valve surgery in the Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, between January and July 2022 were initially enrolled. Eligible patients were randomly assigned at a 1 : 1 ratio to either the RIPC group or the control group. Relevant indicators of heart rate variability [standard deviation of NN interval (SDNN), standard deviation of mean value of NN interval in every five minutes (SDANN), mean square root of difference between consecutive NN intervals (RMSSD), percentage of adjacent RR interval>50 ms (PNN50), low frequency (LF) component, high frequency (HF) component and LF/HF] at 8 hours in the morning on the surgical day between two groups were compared. Results A total of 118 patients were initially assessed. After screening, 58 patients were excluded, and 60 patients provided written informed consent and were enrolled in the trial, with 30 allocated to the RIPC group and 30 to the control group. Seven patients in the control group and 5 patients in the RIPC group were subsequently excluded due to missing heart rate variability data resulting from cancelled operations. Finally, 23 patients in the control group and 25 patients in the RIPC group were included in the analysis. There was no statistical difference in baseline characteristics between the two groups, and there was no significant difference in heart rate variability 24 hours before intervention (P>0.05). After the intervention measures were taken, the comparison of the results of heart rate variability at 8 hours on the day of operation showed that SDNN and SDANN of patients in the RIPC group were higher than those in the control group, with statistical differences (P<0.05). Conclusion RIPC can stabilize the preoperative heart rate variability of patients undergoing cardiac valve surgery.

Objective To compare the mid- and long-term clinical results of mitral valve plasty (MVP) and mitral valve replacement (MVR) in the treatment of functional mitral regurgitation (FMR). Methods Patients with FMR who underwent surgical treatment in the Department of Cardiovascular Surgery of the General Hospital of Northern Theater Command from 2012 to 2021 were collected. The patients who underwent MVP were divided into a MVP group, and those who underwent MVR into a MVR group. The clinical data and mid-term follow-up efficacy of two groups were compared. Results Finally 236 patients were included. There were 100 patients in the MVP group, including 53 males and 47 females, with an average age of (61.80±8.03) years. There were 136 patients in the MVR group, including 72 males and 64 females, with an average age of (61.29±8.97) years. There was no statistical difference in baseline data between the two groups (P＞0.05). There was no statistical difference between the two groups in the extracorporeal circulation time, aortic occlusion time, postoperative hospital and ICU stay, intraoperative blood loss, or hospitalization death (P＞0.05), but the time of mechanical ventilation in the MVP group was significantly shorter than that in the MVR group (P=0.022). The total follow-up rate was 100.0%, the longest follow-up was 10 years, and the average follow-up time was (3.60±2.55) years. There were statistical differences in the left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter and cardiac function between the two groups compared with those before surgery (P<0.05). The postoperative left ventricular ejection fraction in the MVP group was statistically higher than that before surgery (P=0.002), but there was no statistical difference in the MVR group before and after surgery (P=0.658). The left atrial diameter in the MVP group was reduced compared with the MVR group (P=0.026). The recurrence rate of mitral regurgitation in the MVP group was higher than that in the MVR group, and the difference was statistically significant (10.0% vs. 1.5%, P=0.003). There were 14 deaths in the MVP group and 19 in the MVR group. The cumulative survival rate (P=0.605) and cardiovascular events-free survival rate (P=0.875) were not statistically significant between the two groups by Kaplan-Meier survival analysis. Conclusion The safety, and mid- and long-term clinical efficacy of MVP in the treatment of FMR patients are better than MVR, and the left atrial and left ventricular diameters are statistically reduced, and cardiac function is statistically improved. However, the surgeon needs to be well aware of the indications for the MVP procedure to reduce the rate of mitral regurgitation recurrence.

Intelligence encompasses various abilities, including logical reasoning, comprehension, self-awareness, learning, planning, creativity, and problem-solving. Extensive research and practical experience suggest that there are sex differences in intellectual development, with females typically maturing earlier than males. However, the key genes and molecular network mechanisms underlying these sex differences in intellectual development remain unclear. To date, Genome-Wide Association Studies (GWAS) have identified 507 genes that are significantly associated with intelligence. This study first analyzed RNA sequencing data from different stages of brain development (from BrainSpan), revealing that during the late embryonic stage, the average expression levels of intelligence-related genes are higher in males than in females, while the opposite is observed during puberty. This study further constructed interaction networks of intelligence-related genes with sex-differential expression in the brain, including the prenatal male network (HELP-M: intelligence genes with higher expression levels in prenatal males) and the pubertal female network (HELP-F: intelligence genes with higher expression levels in pubertal females). The findings indicate that the key genes in both networks are Ep300 and Ctnnb1. Specifically, Ep300 regulates the transcription of 53 genes in both HELP-M and HELP-F, while Ctnnb1 regulates the transcription of 45 genes. Ctnnb1 plays a more prominent role in HELP-M, while Ep300 is more crucial in HELP-F. Finally, this study conducted sequencing validation on rats at different developmental stages, and the results indicated that in the prefrontal cortex of female rats during adolescence, the expression levels of the intelligence genes in HELP-F, as well as key genes Ep300 and Ctnnb1, were higher than those in male rats. These genes were also involved in neurodevelopment-related biological processes. The findings reveal a sex-differentiated intelligence gene network and its key genes, which exhibit varying expression levels during the neurodevelopmental process.
Female ; Intelligence/physiology* ; Male ; Sex Characteristics ; Animals ; Brain/growth & development* ; E1A-Associated p300 Protein/physiology* ; beta Catenin/physiology* ; Transcriptome ; Rats ; Gene Expression Profiling ; Genome-Wide Association Study

AIM To investigate the impact of varying dosages of Supplemented Wendan Decoction on the PI3K/Akt/FOXO1 glycolipid metabolic pathway in 3T3-L1 adipocytes.METHODS The CCK-8 assay was used to determine the concentration of Supplemented Wendan Decoction-medicated serum.The mature adipocytes differentiated from 3T3-L1 preadipocytes after induction were further divided into the blank control group,the model group,the rosiglitazone group(10 mg/L),and the Supplemented Wendan Decoction groups(5％,10％,and 20％),followed by the sample collections after 48 hours of treatment.Oil red O staining quantified lipid accumulation in 3T3-L1 adipocytes;extracellular glucose levels were measured using glucose oxidase(GOD)assay;RT-qPCR analyzed mRNA expressions of IRS-1,PI3K,Akt,GLUT4,IL-6,TNF-α and IL-1β;Western blot assessed protein expressions of INSR,IRS-1,PI3K-p85,Akt,FOXO1 and GLUT4.RESULTS No significant changes in cell viability(P＞0.05)were observed in 3T3-L1 preadipocytes exposed to serum containing supplemented Wendan Decoction at different concentrations for 24,48,or 72 hours.The 3T3-L1 preadipocytes held the capacity to differentiate into mature adipocytes within a 14-day induction period.Compared to the model group,all supplemented Wendan Decoction groups exhibited reduced lipid accumulation in adipocytes and downregulated mRNA expression of IRS-1,IL-6,TNF-α and IL-1β(P＜0.01);the low-dose group demonstrated increased mRNA expressions of PI3K and GLUT4(P＜0.05,P＜0.01),alongside elevated protein expressions of INSR,IRS-1,PI3K-p85,Akt and GLUT4(P＜0.05,P＜0.01);the medium-dose group showed enhanced GLUT4 mRNA expression,and upregulated protein expressions of INSR and FOXO1(P＜0.01).After 24 hours intervention,the high-dose Supplemented Wendan Decoction group exhibited increased glucose consumption in adipocytes(P＜0.01),and elevated protein expression of INSR,Akt and FOXO1(P＜0.05,P＜0.01).CONCLUSION Supplemented Wendan Decoction reduces lipid accumulation in adipocytes,regulates glucose and lipid metabolism,and promotes metabolic homeostasis through PI3K/Akt/FOXO1 signaling pathway.

Objective:To investigate the curative effect and possible mechanism of rifaximin treatment on monocrotaline-induced hepatic sinusoidal obstruction syndrome (HSOS) in mice.Methods:Twenty-four male C57BL/6J mice were divided into three groups and treated with solvent control, monocrotaline, and rifaximin, respectively. The histopathological changes of the liver and intestine were observed by hematoxylin-eosin staining. The differences were compared in liver parameters, serum liver enzymes, inflammatory factors, apoptotic factors, gut microbiota, and gut tight junction proteins among three groups of mice. The inter-group comparison was conducted using a t-test and one-way analysis of variance.Results:The rifaximin-treated group had significantly improved liver histopathology. The serological levels of alanine aminotransferase and aspartate aminotransferase were (559.04±89.42) U/L and (676.90±106.25) U/L, respectively, which were significantly lower than those in the PA-HSOS model group [(846.05±148.46) U/L and (953.87±58.10) U/L, P<0.05], and were accompanied by lower levels of apoptotic cells and inflammatory factors. Additionally, the rifaximin-treated mice group gut microbiota had higher diversity compared with the PA-HSOS group ( P<0.05), and the Shannon index was 7.77±0.10 and 7.16±0.07, respectively, indicating apparent differences in microbiota among different groups. The abundance of Firmicutes in the rifaximin group was 39.58%±0.56%, which was significantly higher than that in the model group (24.25%±0.64%, P<0.05), while the abundance of Bacteroidetes was 54.7%±0.41%, which was significantly lower than that in the model group (70.92%±0.49%, P<0.05). Simultaneously, the expressions of gut tight junction proteins ZO-1 and Occludin showed an upward trend and validated transcription levels compared to the model group following rifaximin intervention ( P<0.05). Conclusion:Rifaximin can alleviate monocrotaline-induced hepatic sinusoidal obstruction syndrome in mice, and its mechanism may be via gut microbiota regulation, which in turn plays a role in improving intestinal barrier function.

Objective:To investigate the effects of baicalin on ferroptosis of mouse fibroblasts (Fbs) under high glucose treatment and its mechanism, and to provide a basis for the treatment of diabetic wounds.Methods:The study was an experimental study. Mouse Fbs were collected and divided into control group with conventional culture, high glucose group treated with glucose at final molarity of 30.0 mmol/L, and low baicalin group and high baicalin group pretreated with baicalin at final molarties of 5 and 10 μmol/L respectively and then treated as that in high glucose group. After 48 h of culture, the cell survival rate was detected by the cell counting kit-8, the reactive oxygen species level in cells was detected by the fluorescent probe method, the levels of malondialdehyde, glutathione, and ferrous ion in cells were detected by colorimetry, and the protein expression levels of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in cells and nuclear factor-erythroid 2-related factor 2 (Nrf2) in cytoplasm and nucleus were detected by Western blotting. Another batch of mouse Fbs were collected and divided into control group, high glucose group, high baicalin group, and high baicalin+ML385 group. The cells in the first three groups were treated as before, the cells in the last group were pretreated with baicalin and ML385 of Nrf2 inhibitor at final molarties of 10 μmol/L and then treated as that in high glucose group. After 48 h of culture, the protein expression levels of SLC7A11 and GPX4 in cells and the protein expression level of Nrf2 in cytoplasm and nucleus were detected as before. Except that the sample number in detecting SLC7A11 and GPX4 was 4, the sample number in detecting other indexes was 3.Results:After 48 h of culture, the cell survival rates in control group, high glucose group, low baicalin group, and high baicalin group were (100.0±10.7)%, (70.0±5.0)%, (80.9±3.2)%, and (91.4±1.9)%, respectively. Compared with those in control group, the cell survival rate, the glutathione level, and SLC7A11 and GPX4 protein expression levels in cells, and nuclear Nrf2 protein expression level were significantly decreased in high glucose group ( P<0.05), and the levels of reactive oxygen species, malondialdehyde, and ferrous ion in cells, and cytoplasmic Nrf2 protein expression level were significantly increased in high glucose group ( P<0.05). Compared with those in high glucose group, the cell survival rate, glutathione level, SLC7A11 and GPX4 protein expression levels in cells, and nuclear Nrf2 protein expression level in low baicalin group and high baicalin group were significantly increased ( P<0.05), the reactive oxygen species and ferrous ion levels in cells, and cytoplasmic Nrf2 protein expression level in low baicalin group and high baicalin group were significantly decreased ( P<0.05), and the malondialdehyde level in cells in high baicalin group was significantly decreased ( P<0.05). Compared with those in low baicalin group, the cell survival rate, glutathione level, SLC7A11 and GPX4 protein expression levels in cells, and nuclear Nrf2 protein expression level in high baicalin group were significantly increased ( P<0.05), and the reactive oxygen species, malondialdehyde, and ferrous ion levels in cells, and cytoplasmic Nrf2 protein expression level in high baicalin group were significantly decreased ( P<0.05). After 48 h of culture, compared with those in control group, the nuclear Nrf2 protein expression level and SLC7A11 and GPX4 protein expression levels in cells were significantly decreased ( P<0.05), and the cytoplasmic Nrf2 protein expression level was significantly increased in high glucose group ( P<0.05); compared with those in high glucose group, the cytoplasmic Nrf2 protein expression level was significantly decreased ( P<0.05), and the nuclear Nrf2 protein expression level and SLC7A11 and GPX4 protein expression levels in cells were significantly increased in high baicalin group ( P<0.05); compared with those in high baicalin group, the cytoplasmic Nrf2 protein expression level was significantly increased ( P<0.05), and the nuclear Nrf2 protein expression level and SLC7A11 and GPX4 protein expression levels in cells were significantly decreased in high baicalin+ML385 group ( P<0.05). Conclusions:Baicalin can inhibit the occurrence of ferroptosis in cells by activating the Nrf2 signaling pathway and up-regulating the expressions of proteins related to SLC7A11/GPX4 axis in Fbs in high glucose treatment, thus increasing the cell survival rate.

Based on commonly used acupoints in the clinical acupuncture treatment of functional dyspepsia （FD）， this study systematically analyzes the therapeutic differences and synergistic effects between local and distal point selection. It also examines the suitability of primary acupoint selection for different FD subtypes， postprandial distress syndrome （PDS） and epigastric pain syndrome （EPS）. The findings suggest that a combination of local and distal acupoints may be more appropriate as primary points for PDS， whereas local acupoints alone may be more suitable for EPS. Additionally， the study explores the impact of various factors， such as stimulation techniques， needling order， intensity or stimulation parameters， and depth， on the efficacy of acupuncture. It concludes that the intrinsic properties of acupoints are the primary determinants of therapeutic direction. Other factors mainly influence the magnitude rather than the direction of the effect. Future research may further investigate how different acupoint combinations， local versus distal， affect the treatment outcomes of FD subtypes， providing new insights for clinical acupuncture prescriptions.

Objective:To investigate the diagnostic value of metagenomic next-generation sequencing (mNGS) for pyogenic spinal infections.Methods:A total of 255 patients diagnosed with pyogenic spinal infections were enrolled between September 2022 and September 2024 at Qingdao University Affiliated Hospital, Fuzhou Second General Hospital, First Affiliated Hospital of Nanchang University, Shandong University Affiliated Public Health Clinical Center, and the Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Among them, 155 were male and 100 were female, with an average age of 62.5±14.2 years (ranging from 13 to 90 years). All patients had samples of infected tissue and/or pus collected for microbial culture and mNGS testing. The number, types, and positive rates of pathogens detected by microbial culture and mNGS were compared. Using culture results as the gold standard, receiver operating characteristic (ROC) curve analysis was performed for mNGS testing and the combined method of mNGS and microbial culture, calculating the area under the curve (AUC) and 95% CI. Results:All 255 cases were clinically diagnosed as pyogenic spinal infections, with 194 cases providing microbiological evidence. The most common Gram-positive bacterium was Staphylococcus aureus, while the most common Gram-negative bacterium was Escherichia coli. A total of 33 pathogenic microorganisms were detected by mNGS, while microbial culture detected 18 pathogenic microorganisms. The positive rate of mNGS was 72.2% (184 out of 255), which was significantly higher than that of 30.2% (77 out of 255) for microbial culture, showing a significant difference (χ 2=90.150, P<0.001); the positive rate of mNGS combined with microbial culture was 76.1% (194 out of 255) with significant difference compared to mNGS alone (χ 2=8.100, P<0.001). Among 178 culture-negative samples, the detection rate of mNGS was 65.7% (117 out of 178); among 77 culture-positive samples, the detection rate of mNGS was 87.0% (67 out of 77), and 97.0% (65 out of 67) of the detected pathogens matched the culture results at the species level. The AUCs of the ROC curves for mNGS testing and the combination of mNGS with microbial culture were 0.606 [95% CI (0.534, 0.678)] and 0.671 [95% CI (0.606, 0.736)], respectively, with significant differences compared to microbial culture ( P=0.007; P=0.007). Conclusions:mNGS demonstrates superior performance over conventional culture in identifying pathogens in pyogenic spinal infections. Moreover, combining mNGS with culture further improves diagnostic yield, supporting its integration into clinical practice.

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal inflammatory disease, which not only affects the digestive tract, but also involves extraintestinal organs and tissues such as joints and eyes, and ultimately endangers human health and affects the quality of life of patients. With the development of information technology, there is an increasing application of digital therapeutics in the management of IBD. This article aims to comprehensively analyze the characteristics, use, and challenges of digital therapeutics in the management of IBD, and explore its potential to improve treatment adherence, disease surveillance, and improve patients' quality of life.