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

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy of the digestive tract that poses a significant threat to human health, with an incidence rate that continues to rise globally. Increasing research highlights the crucial role of non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in regulating ferroptosis and contributing to the malignant progression of ESCC. These ncRNAs influence the proliferation, apoptosis, and invasion capabilities of ESCC cells by modulating iron metabolism and redox balance. miRNAs can regulate cellular iron accumulation and oxidative stress by targeting ferroptosis-related genes; lncRNAs may indirectly affect iron metabolic pathways by competitively binding to miRNAs; circRNAs, through a sponge effect, may regulate the activity of miRNAs. This review systematically summarizes the mechanisms of ncRNAs-mediated regulation of ferroptosis in ESCC, focusing on molecular mechanisms, regulatory networks, and their specific roles in the ferroptosis process. Additionally, the potential of ncRNAs in ESCC diagnosis, prognosis assessment, and therapeutic intervention is discussed, aiming to provide new insights and targets for ferroptosis-based tumor therapy.
Ferroptosis/genetics* ; Humans ; Esophageal Neoplasms/physiopathology* ; Esophageal Squamous Cell Carcinoma ; MicroRNAs/physiology* ; RNA, Long Noncoding/physiology* ; RNA, Circular ; RNA, Untranslated/physiology*

OBJECTIVE: To investigate the effects of combined platelet-rich plasma (PRP) and arterial supercharging technique on the survival rate and functional restoration of cross-body region skin flaps in rabbits. METHODS: Twelve healthy 6-month-old New Zealand White rabbits were randomly assigned to 4 groups ( n=3): sham group, PRP group, anastomosis group, and combined treatment group. An axial skin flap with an area of 12 cm×6 cm on the inner side of the hind limbs of all animals were prepared, with the saphenous artery as the main blood supply. Following the ligation of both the proximal and distal ends of the saphenous artery across all groups, the sham group received no further intervention, the PRP group was subjected to PRP injection, the anastomosis group underwent in situ end-to-end anastomosis of the distal saphenous artery, and the combined treatment group received both in situ distal saphenous artery anastomosis and PRP administration. Flap survival was evaluated and recorded on postoperative days 1, 3, and 7, with survival rates calculated accordingly. On day 7, flap tissue samples were harvested for HE staining to assess basal tissue morphology. Additionally, immunohistochemical staining was conducted to detect the expression of α-smooth muscle actin (α-SMA), vascular endothelial growth factor (VEGF), and CD31 in the flap tissues. RESULTS: At postoperative day 1, no significant difference in flap survival rates were observed among the 4 groups ( P>0.05). At day 3, the PRP group showed no significant difference compared to the sham group ( P>0.05); however, both the anastomosis and combined treatment groups exhibited significantly higher survival rates than the sham group ( P<0.05), the combined treatment group further demonstrated superior survival rates compared to both the PRP and anastomosis groups ( P<0.05). At day 7, the combined treatment group maintained significantly higher survival rates than all other groups ( P<0.05), while both the PRP and anastomosis groups exceeded the sham group ( P<0.05). HE staining at day 7 revealed persistent inflammatory cell infiltration, sheet-like erythrocyte deposition, and disordered collagen fibers in the sham group. The PRP group showed nascent microvessel formation and early collagen reorganization, whereas the anastomosis group displayed mature microvasculature with resolved interstitial edema. The combined treatment group exhibited differentiated microvessels with densely packed collagen bundles. Immunohistochemical analysis at day 7 demonstrated significantly larger relative area percentages of α-SMA, VEGF, and CD31 positive cells in the combined treatment group compared to all other groups ( P<0.05). Both the PRP and anastomosis groups also showed significantly higher values than the sham group ( P<0.05). CONCLUSION The combination of PRP and arterial supercharging techniques significantly enhances flap healing, potentially through mechanisms involving augmented angiogenesis and improved blood supply.
Animals ; Rabbits ; Platelet-Rich Plasma ; Surgical Flaps/blood supply* ; Graft Survival ; Anastomosis, Surgical/methods* ; Ischemia/surgery* ; Arteries/surgery* ; Skin/blood supply* ; Vascular Endothelial Growth Factor A/metabolism* ; Male ; Skin Transplantation/methods*

PURPOSE: To investigate the incidence and influencing factors of bone loss in patients with spinal cord injury (SCI). METHODS: A retrospective case-control study was conducted. Patients with SCI in our hospital from January 2019 to March 2023 were collected. According to the correlation between bone mineral density (BMD) at different sites, the patients were divided into the lumbar spine group and the hip joint group. According to the BMD value, the patients were divided into the normal bone mass group (t > -1.0 standard deviation) and the osteopenia group (t ≤ -1.0 standard deviation). The influencing factors accumulated as follows: gender, age, height, weight, cause of injury, injury segment, injury degree, time after injury, start time of rehabilitation, motor score, sensory score, spasticity, serum value of alkaline phosphatase, calcium, and phosphorus. The trend chart was drawn and the influencing factors were analyzed. SPSS 26.0 was used for statistical analysis. Correlation analysis was used to test the correlation between the BMD values of the lumbar spine and bilateral hips. Binary logistic regression analysis was used to explore the influencing factors of osteoporosis after SCI. p < 0.05 was considered statistically significant. RESULTS: The incidence of bone loss in patients with SCI was 66.3%. There was a low concordance between bone loss in the lumbar spine and the hip, and the hip was particularly susceptible to bone loss after SCI, with an upward trend in incidence (36% - 82%). In this study, patients with SCI were divided into the lumbar spine group (n = 100) and the hip group (n = 185) according to the BMD values of different sites. Then, the lumbar spine group was divided into the normal bone mass group (n = 53) and the osteopenia group (n = 47); the hip joint group was divided into the normal bone mass group (n = 83) and the osteopenia group (n = 102). Of these, lumbar bone loss after SCI is correlated with gender and weight (p = 0.032 and < 0.001, respectively), and hip bone loss is correlated with gender, height, weight, and time since injury (p < 0.001, p = 0.015, 0.009, and 0.012, respectively). CONCLUSIONS The incidence of bone loss after SCI was high, especially in the hip. The incidence and influencing factors of bone loss in the lumbar spine and hip were different. Patients with SCI who are male, low height, lightweight, and long time after injury were more likely to have bone loss.
Humans ; Spinal Cord Injuries/complications* ; Male ; Female ; Retrospective Studies ; Incidence ; Adult ; Bone Density ; Middle Aged ; Case-Control Studies ; Osteoporosis/etiology* ; Lumbar Vertebrae ; Bone Diseases, Metabolic/etiology* ; Aged ; Risk Factors

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective: To explore the mediating role of psychological and physical aggression in the association between maternal emotional symptoms with emotional and behavioral problems in preschool children, so as to provide references for effective intervention of risk factors related to childrens emotional and behavioral problems. Methods: A longitudinal study was conducted to select 12 kindergarten children and their mothers in Wuhu City, Anhui Province by using stratified clustering sampling. The baseline survey was carried out in June 2021, followed up every six months, and a total of 3 followups were administered. Totally 853 valid questionnaires of junior class children were included by the survey data from baseline, second and thirl followups. The Depression Anxiety and Stress Scale-21 (DASS-21), the Parent-Child Conflict Tactics Scales (CTSPC) and the Strength and Difficulties Questionnaire (SDQ) were used to measure maternal emotional symptoms, psychological and physical aggression, and childrens emotional and behavioral problems, respectively. Results: The physical aggression of mothers towards children in boys was higher than in girls (t=3.53, P<0.05). The results of correlation analysis showed that maternal depressive symptoms were positively correlated with psychological aggression, physical aggression and childrens SDQ scores (r=0.20, 0.21, 0.18, P<0.01), maternal anxiety symptoms were positively correlated with psychological aggression, physical aggression and childrens SDQ scores (r=0.24, 0.22, 0.10, P<0.01), respectively; maternal stress symptoms were positively correlated with psychological aggression, physical aggression. The SDQ scores were positively correlated (r=0.26, 0.25, 0.18, P<0.01), and the scores of maternal psychological aggression and physical aggression were positively correlated with the SDQ scores of children (r=0.12, 0.16, P<0.01). The mediating analysis showed that after controlling for related confounding factors, psychological aggression played a partial mediating effect in the association between maternal depressive symptoms and childrens emotional and behavioral problems, and the mediating effect ratio was 8.05%. Physical aggression played a partial mediating effect in the association between maternal depression, anxiety and stress symptoms and childrens emotional and behavioral problems, which were 15.94%, 11.73% and 12.54% (P<0.05), respectively. Conclusions Psychological and physical aggression play mediating roles in the association between maternal emotional symptoms and childrens emotional and behavioral problems, and actively improving maternal emotional symptoms and their childrens discipline methods can help reduce the occurrence of emotional and behavioral problems in preschool children.

ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

GNPS-based mass spectrum-molecular networks is an effective strategy for rapidly identifying known natural products and discovering novel structures. The chemical diversity of azaphilones from the fermentation extracts of Talaromyces sp. HK1-18 was studied by molecular network technique. Three linear tricyclic azaphilones, sequoiamonacins A-C (2a, 2b, 1), were isolated by silica gel column chromatography and high performance liquid chromatography from the extracts of the fungal strain of HK1-18, and their structures were identified by nuclear magnetic resonance and high-resolution mass spectrometry. Guided by the mass spectra of sequoiamonacins A-C (2a, 2b, 1), the cluster of sequoiamonacinoid analogues was discovered from the full molecular networking of HK1-18. By analyzing the MS/MS fragments of each parent ion in this cluster, 7 azaphilones (3-9) included 6 new ones (4-9) were predicted successfully. Then the MS/MS cracking regularity of this type of azaphilones was revealed. Compound 1 showed anti-inflammatory activity, which can inhibit the production of interleukin-1α (IL-1α) in lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7, with an inhibitory rate of 29% at the concentration of 12.5 μg·mL^-1.