ObjectiveMagnetoencephalography (MEG), a non-invasive neuroimaging technique, meticulously captures the magnetic fields emanating from brain electrical activity. Compared with MEG based on superconducting quantum interference devices (SQUID), MEG based on optically pump magnetometer (OPM) has the advantages of higher sensitivity, better spatial resolution and lower cost. However, most of the current studies are clinical studies, and there is a lack of animal studies on MEG based on OPM technology. Pain, a multifaceted sensory and emotional phenomenon, induces intricate alterations in brain activity, exhibiting notable sex differences. Despite clinical revelations of pain-related neuronal activity through MEG, specific properties remain elusive, and comprehensive laboratory studies on pain-associated brain activity alterations are lacking. The aim of this study was to investigate the effects of inflammatory pain (induced by Complete Freund’s Adjuvant (CFA)) on brain activity in a rat model using the MEG technique, to analysis changes in brain activity during pain perception, and to explore sex differences in pain-related MEG signaling. MethodsThis study utilized adult male and female Sprague-Dawley rats. Inflammatory pain was induced via intraplantar injection of CFA (100 μl, 50% in saline) in the left hind paw, with control groups receiving saline. Pain behavior was assessed using von Frey filaments at baseline and 1 h post-injection. For MEG recording, anesthetized rats had an OPM positioned on their head within a magnetic shield, undergoing two 15-minute sessions: a 5-minute baseline followed by a 10-minute mechanical stimulation phase. Data analysis included artifact removal and time-frequency analysis of spontaneous brain activity using accumulated spectrograms, generating spectrograms focused on the 4-30 Hz frequency range. ResultsMEG recordings in anesthetized rats during resting states and hind paw mechanical stimulation were compared, before and after saline/CFA injections. Mechanical stimulation elevated alpha activity in both male and female rats pre- and post-saline/CFA injections. Saline/CFA injections augmented average power in both sexes compared to pre-injection states. Remarkably, female rats exhibited higher average spectral power 1 h after CFA injection than after saline injection during resting states. Furthermore, despite comparable pain thresholds measured by classical pain behavioral tests post-CFA treatment, female rats displayed higher average power than males in the resting state after CFA injection. ConclusionThese results imply an enhanced perception of inflammatory pain in female rats compared to their male counterparts. Our study exhibits sex differences in alpha activities following CFA injection, highlighting heightened brain alpha activity in female rats during acute inflammatory pain in the resting state. Our study provides a method for OPM-based MEG recordings to be used to study brain activity in anaesthetized animals. In addition, the findings of this study contribute to a deeper understanding of pain-related neural activity and pain sex differences.

This article reports the clinical features and gene mutation types of a large family with Nascimento form of syndromic X-linked intellectual developmental disorder (MRXSN), involving 9 individuals across 3 generations, and a literature review was conducted. In this family, 9 individuals had similar manifestations including mental retardation and unusual facies, and 4 of them had passed away. Genetic testing showed that the proband had the deletion of exons 2-3 of the UBE2A gene, which was inherited from the mother. Fluorescent quantitative polymerase chain reaction showed that the proband and his uncle had the deletion of exons 2-3 of the UBE2A gene; the proband's mother, grandmother, and great-aunt had a heterozygous deletion of exons 2-3 of the UBE2A gene; the proband's father, sister, and aunt had a normal copy number of exons 2-3 of the UBE2A gene. The 34 patients reported in the literature had diverse clinical phenotypes, and UBE2A gene mutations (22/34, 65%) and large fragment deletions (12/34, 35%) were the main mutation types. Moderate to severe mental retardation (34/34, 100%), speech and language impairment (33/34, 97%), and unusual facies (32/34, 94%) were the main clinical manifestations of MRXSN patients. The disease has obvious phenotypic heterogeneity, and early diagnosis facilitates optimal prenatal and postnatal management to improve reproductive outcomes.
Humans ; Male ; Ubiquitin-Conjugating Enzymes/genetics* ; Female ; X-Linked Intellectual Disability/genetics* ; Gene Deletion ; Child ; Pedigree ; Child, Preschool ; Adult

OBJECTIVE: To investigate the expression and clinical significance of interleukin-10 (IL-10) and interleukin-15 (IL-15) in patients with multiple myeloma (MM). METHODS: Eighty newly diagnosed MM patients in Department of Hematology in Nanyang First People's Hospital from September 2020 to January 2023 were selected as observation group, and 80 healthy people in our hospital were selected as control group. The expression of IL-10 and IL-15 of the two groups were detected, and survival analysis was conducted for the MM patients. RESULTS: The levels of IL-10 and IL-15 in the observation group before treatment were significantly higher than those in the control group (both P <0.05). The levels of IL-10 and IL-15 in different DS stage had significant differences in MM patients (both P <0.05). The levels of IL-10 and IL-15 in stage II and stage III had no significant differences, which were both significantly higher than those in stage I (both P <0.05). The levels of IL-10 and IL-15 in sCR+CR group after treatment were significantly lower than those before treatment (both P <0.05). The levels of IL-10 and IL-15 in VGPR+PR group after treatment were also significantly lower than those before treatment (both P <0.05), but higher than those in the sCR+CR group (both P <0.05). The progression-free survival (PFS) and overall survival (OS) of patients with IL-10>22.01 pg/ml were significantly shorter than those with IL-10≤22.01 pg/ml (both P <0.001). The PFS and OS of patients with IL-15>48.56 pg/ml were also shorter than those with IL-15≤48.56 pg/ml (both P <0.05). CONCLUSIONS The levels of IL-10 and IL-15 in MM patients are closely related to efficacy and prognosis, and both decreased after treatment. The more reduction, the better effect. Patients with IL-10 and IL-15 below the threshold have longer median PFS and OS.
Humans ; Interleukin-10/metabolism* ; Multiple Myeloma/metabolism* ; Interleukin-15/metabolism* ; Prognosis ; Female ; Male ; Middle Aged ; Clinical Relevance

Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc ^Min/+ mice and clinical patients. There was a marked accumulation of CCL22⁺ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22⁺ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22⁺ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.

Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
Animals ; tau Proteins/metabolism* ; Alzheimer Disease/metabolism* ; Fibrinogen/metabolism* ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Memory Disorders/metabolism* ; Male ; Mice, Inbred C57BL ; Brain/metabolism* ; Hippocampus/metabolism* ; Protein Aggregation, Pathological/metabolism* ; Apoptosis ; Phosphorylation

OBJECTIVE: Several epidemiological observational studies have related particulate matter (PM) exposure to Inflammatory bowel disease (IBD), but many confounding factors make it difficult to draw causal links from observational studies. The objective of this study was to explore the causal association between PM _2.5 exposure, its absorbance, and IBD. METHODS: We assessed the association of PM _2.5 and PM _2.5 absorbance with the two primary forms of IBD (Crohn's disease [CD] and ulcerative colitis [UC]) using Mendelian randomization (MR) to explore the causal relationship. We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study. Single-nucleotide polymorphisms linked with PM _2.5 concentrations or their absorbance were used as instrumental variables (IVs). We used inverse variance weighting (IVW) as the primary analytical approach and four other standard methods as supplementary analyses for quality control. RESULTS: The results of MR demonstrated that PM _2.5 had an adverse influence on UC risk (odds ratio [ OR] = 1.010; 95% confidence interval [ CI] = 1.001-1.019, P = 0.020). Meanwhile, the results of IVW showed that PM _2.5 absorbance was also causally associated with UC ( OR = 1.012; 95% CI = 1.004-1.019, P = 0.002). We observed no causal relationship between PM _2.5, PM _2.5 absorbance, and CD. The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy, ensuring the reliability of MR results. CONCLUSION Based on two-sample MR analyses, there are potential positive causal relationships between PM _2.5, PM _2.5 absorbance, and UC.
Humans ; Mendelian Randomization Analysis ; Particulate Matter/analysis* ; Polymorphism, Single Nucleotide ; Inflammatory Bowel Diseases/genetics* ; Air Pollutants/analysis* ; Crohn Disease/genetics* ; Colitis, Ulcerative/genetics* ; Genome-Wide Association Study ; Risk Factors ; Environmental Exposure

Objective:To explore the perioperative safety and postoperative efficacy of prophylactic jejunal nutrition tube placement during early gastric body cancer pylorus-preserving gastrectomy (PPG).Methods:The clinical data of 29 gastric cancer patients treated by Beijing Friendship Hospital, Capital Medical University from January 2018 to December 2024 were retrospectively analyzed. There were 17 males (58.6%) and 12 females (41.4%), aged from 43 to 74 years, with an average age of (58.9 ± 8.3) years, and an average body mass index (BMI) of (24.3 ± 3.0) kg/m 2. According to the type of catheterization, all cases were divided into jejunal nutrition tube group ( n=12) and gastric tube group( n=17). The main outcome was the incidence of delayed gastric emptying within one month after surgery in both groups. Statistical analysis was conducted using SPSS26.0 software. Results:Patients in the jejunal feeding tube group resumed oral liquid intake, soft diet and regular diet significantly earlier postoperatively compared to those in the gastric tube group, with statistically significant differences ( P<0.05). Conversely, the time to removal of the tube was significantly earlier in the gastric tube group than in the jejunal feeding tube group ( P<0.05). However, the proportion of patients requiring reinsertion of a gastric or jejunal feeding tube postoperatively was significantly higher in the gastric tube group (7 cases) compared to the jejunal feeding tube group (0 case) ( P<0.05). In the jejunal feeding tube group, there were 4 cases occurred DGE, in the gastric tube group, there were 8 cases occurred DGE. There were no statistically significant differences between the two groups in either the overall incidence of DGE or the distribution of DGE severity grades. On postoperative 7th day , the Gastric Outlet Obstruction Scoring System (GOOSS) grade was significantly better in the jejunal feeding tube group than in the gastric tube group ( P<0.05), and all patients in the jejunal feeding tube group had resumed liquid intake, compared to only 58.8% in the gastric tube group. Conclusions:Compared with gastric tube placement, intraoperative prophylactic jejunal feeding tube placement for PPG has significant advantages in perioperative safety and postoperative recovery, but large-sample prospective studies are still needed for further verification.

Objective To investigate the association of digit ratio with single nucleotide polymorphism(SNP)at three loci(rs17576,rs3918249,rs9509)of matrix metallopeptidase 9(MMP-9)gene.Methods A total of 804 Ningxia Han youths(399 males and 405 females)were used as the study subjects.A digital camera was used to take frontal photographs of the hands,and image analysis software was used to mark the anatomical points and measure the lengths of each finger of both hands(2D,3D,4D,5D);Multiplexed PCR was used to detect the three polymorphic sites of the MMP-9 gene,SPSS 25.0 and R Studio software were used for data analysis and plotting.Results The 2D/3D(P＜0.05)and 2D/4D(left,P＜0.01,right,P＜0.05)of both hands,2D/5D(P＜0.01),3D/5D,4D/5D(P＜0.05)of the right hand,and 3D/4D(P＜0.05)of the left hand in female youths of Ningxia Han were significantly higher than those in males,Differences in genotypes and allele frequencies at all 3 loci of the MMP-9 gene were not statistically significant between genders(P＞0.05).Right hand 2D/4D was significantly associated with genotypes at the rs17576 and rs3918249 loci in male youths(P＜0.05).Conclusion MMP-9 gene SNPs(rs17576 and rs3918249)may be associated with the formation of 2D/4D of Ningxia Han male youths.

Objective To explore the effect of transjugular intrahepatic portosystemic shunt(TIPS)on gut microbiota and blood ammonia level in patients with decompensated cirrhosis,and to analyze the correlation between the gut microbiota and blood ammonia level.Methods From July 2021 to December 2023,the patients with decompensated cirrhosis and portal hypertension complicated by esophagogastric variceal bleeding and/or refractory ascites,who received TIPS at Zhuhai Hospital of Guangdong Provincial Hospital of Traditional Chinese Medicine,were collected.The blood and stool samples were collected before and after TIPS.The changes in blood routine,prothrombin time,liver function,and blood ammonia level were determined.The change of gut microbiota was detected using 16S rRNA high-throughput sequencing,and Spearman correlation analysis was used to assess the correlation between the gut microbiota and blood ammonia level.Results In 20 patients,the post-TIPS one-month levels of AST,TBil,DBiL,PT,and blood ammonia were higher than their pre-TIPS values(P＜0.05),and the albumin(Alb)level was lower than the pre-TIPS value(P＜0.05).The post-TIPS 3-month levels of TBil,DBil,PT,and blood ammonia were higher than their pre-TIPS values(P＜0.05).One month after TIPS,the beta diversity of the gut microbiota became significantly different from the pre-TIPS pattern(P＜0.05).After TIPS,the harmful bacteria such as Veillonella,Streptococcus and Haemophilus were significantly reduced,the difference was statistically significant(P＜0.05).The correlation analysis of gut microbiota and blood ammonia level showed that in T0 group Colidextribacter was positively correlated with blood ammonia level,while Roxobella was negatively correlated with blood ammonia level;and in T1 group,Colidextribacter and Streptococcus were positively correlated with blood ammonia level,while Coprococcus,Bifidobacterium and Parasutterella were negatively correlated with blood ammonia level,and the differences were statistically significant(all P＜0.05).Conclusion In patients with decompensated cirrhosis after receiving TIPS,significant changes in the pattern of gut microbiota occur.Certain correlations exist between the changes of some microbiota and blood ammonia levels.Regulating the intestinal microecology may contribute to reducing blood ammonia level after TIPS.

Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.