Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

In order to adapt to teaching reform of Medical Immunology and create a"golden course",through teaching prac-tice,our research group proposes a"three-dimensional curriculum teaching system",which organically combines teaching concepts with teaching design and process,with construction of various resources(material libraries),and finally,multi-level teaching evalua-tion is completed to achieve overall unity of teaching.

Objective To investigate the effects of chronic restraint stress for 28 days(day and night)on mood and cognitive-like behavior in male and female ICR mice,to provide a basis for the selection of sex and restraint period in chronic restraint stress model animals.Methods A total of 72 male and female(1∶1)ICR mice were divided into six groups:male control,daytime restraint,and nighttime restraint groups,and female control,daytime restraint,and nighttime restraint groups.Mice in all but the control groups were bound for 10 h/d and restrained continuously for 28 days to establish a chronic restraint stress model.The emotional and cognitive behaviors induced by restraint in male and female mice at different times were observed by open field,Y maze,novel inhibition feeding,elevated cross maze,tail suspension,forced swimming,and dark-avoidance experiments.Results In the tail suspension experiment,the immobility time of male mice in the daytime restraint group was significantly increased compared with that in the control group(P＜0.05),and the immobility times of male mice in the daytime and nighttime restraint groups were also significantly increased in the forced swimming experiment,compared with those in the control group(P＜0.05).There was no significant difference between the female daytime restraint and female control groups in the novelty inhibition feeding experiment,but the feeding latency of the nighttime restraint group was significantly longer than that of the control group(P＜0.05)and the daytime restraint group(P＜0.05).The feeding latency of female mice was significantly longer than that of males during nighttime restraint(P＜0.05).In the open field test,compared with the male control group,the female control group showed a significant decrease in central area time and the ratio of central area time to peripheral area time(P＜0.05).Compared with the female control group,the female daytime restraint group exhibited a significant decrease in central area time and the ratio of central area time to peripheral area time(P＜0.05).There was no significant difference between the groups in the elevated cross maze and Y maze experiments.There was no significant difference in dark latency between the daytime restraint group and the control group,but darkness latency was significantly shorter in the nighttime restraint group compared with those in the control group(P＜0.05).When male and female mice were combined,the immobility time in the daytime restraint group was significantly increased in the tail suspension experiment(P＜0.05),the immobility times of mice in the daytime and nighttime restraint groups were significantly increased in the forced swimming experiment(P＜0.01,P＜0.05),and the central zone time and the ratio of central area time to peripheral area time of daytime restraint mice were significantly shorter compared with those in the control group(P＜0.05,P＜0.01).There was no significant difference in the central zone time and the ratio of central area time to peripheral area time in the nighttime restraint groups,and no significant difference in average speed or total distance between the daytime and nighttime restraint groups.Conclusions Male mice exhibited depression after 28 d of chronic restraint stress during the daytime,while female mice were prone to anxiety after 28 d of chronic restraint stress.Male mice experienced learning and memory impairment after 28 d of chronic restraint stress during the night.

Objective To explore the role and mechanism of RNA m6A methyltransferase Wilms'tumor 1-associated protein(WTAP)in epithelial-mesenchymal transition(EMT)of glioblastoma cells and its association with transcription factor JUNB.Methods(1)Based on the Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases,the expression levels of transforming growth factor β(TGF-β),WTAP,and JUNB in glioblastoma multiforme(GBM)and normal brain tissues were analyzed,as well as their diagnostic and prognostic values for GBM.The correlation of TGF-β,WTAP,and JUNB with gliomas of different WHO grades was analyzed using the Chinese Glioma Genome Atlas(CGGA)database.Spearman correlation analysis was performed to assess the correlation between TGF-β and m6A methyltransferases.(2)An EMT model was established in human astrocytoma U87-MG cells through TGF-β1 induction.qRT-PCR and Western blotting were employed to detect the expression levels of WTAP,JUNB,matrix metalloproteinase 2(MMP2),and N-cadherin.The migration capacity of U87-MG cells was evaluated by wound-healing and Transwell assays.An m6A RNA methylation quantification kit(colorimetric)was used to detect RNA m6A methylation modification levels.A stable cell line with low expression of WTAP was constructed to investigate the effects of WTAP knockdown on the migration ability of U87-MG cells,as well as the expression of JUNB.(3)A protein-protein interaction network was constructed using STRING database and GeneMANIA database,followed by gene ontology(GO)and KEGG pathway enrichment analyses to explore the biological processes,molecular functions,cellular components,and signaling pathways potentially involved in TGF-β/WTAP/JUNB.Gene set enrichment analysis(GSEA)was performed on JUNB-related genes to investigate their potential downstream signaling pathways.Results(1)The expression levels of TGF-β,WTAP,and JUNB were significantly higher in GBM(P<0.001),positively correlated with WHO grades of glioma(P<0.001).Glioma patients with high expression of all three genes had shorter overall and disease-free survival(P<0.001).Spearman analysis showed that the expression of TGF-β in GBM was positively correlated with WTAP(r=0.175,P=0.023),but no significant correlation with other m6A methyltransferases(P>0.05).(2)After TGF-β1 treatment,the level of m6A methylation modification of total RNA in U87-MG cells significantly increased(P<0.001).Wound-healing assay and Transwell assay results showed that the migration ability of U87-MG cells was significantly increased after TGF-β1 treatment(P<0.01),while WTAP knockdown significantly reduced the migration ability of U87-MG cells(P<0.01).qRT-PCR and Western blotting results showed that the mRNA and protein expression levels of WTAP,N-Cadherin,MMP2,and JUNB in U87-MG cells were significantly increased after 48 h of TGF-β1 induction(P<0.001),while WTAP knockdown significantly reduced the mRNA and protein expression of JUNB(P<0.001).(3)The TGF-β/WTAP/JUNB-related protein-protein interaction network was constructed,which was primary involved in mRNA modification and EMT.GSEA results showed that JUNB-related signaling pathways were closely associated with glioma malignant progression.Conclusions TGF-β,WTAP,and JUNB are all associated with GBM malignant progression and poor patient prognosis.TGF-β may enhance total RNA m6A modification by promoting the expression of m6A methyltransferase WTAP,and WTAP subsquentaly upregulates transcription factor JUNB,thereby promoting EMT and malignant progression of GBM.

In order to adapt to teaching reform of Medical Immunology and create a"golden course",through teaching prac-tice,our research group proposes a"three-dimensional curriculum teaching system",which organically combines teaching concepts with teaching design and process,with construction of various resources(material libraries),and finally,multi-level teaching evalua-tion is completed to achieve overall unity of teaching.

To investigate the role of the DPP4-nestin axis in liver fibrosis induced by alveolar cyst infection,a murine model was established using C57BL/6 mice via hepatic portal vein injection.Liver histopathological changes were assessed using HE staining,while immunohistochemistry and immunofluorescence were employed to evaluate the expression levels of nestin and DPP4 in infected mouse livers.In vitro,J S1 cell line was stimulated with recombinant DPP4 protein to es-tablish a cellular model,and qPCR,Western blot,and shRNA lentivirus interference techniques were utilized to examine the involvement of the DPP4-nestin axis in hepatic stellate cell activation.The findings demonstrated that compared to the Sham group,liver tissue structure disruption and collagen deposition were evident along with significantly increased expressions of nestin and DPP4(P＜0.050 0),which colocalized with nesin and α-SMA.Furthermore,stimulation with recombi-nant DPP4 protein significantly enhanced JS1 cell activation(P＜0.050 0)as well as upregulated nestin expression(P＜0.050 0)when compared to control group cells.Notably,shRNA lentivirus-mediated inhibition of nestin expression effectively suppressed the activating effects exerted by re-combinant DPP4 protein on JS1 cells(P＜0.050 0).Collectively,these results highlight the crucial regulatory role played by the DPP4-nestin axis in hepatic stellate cell activation triggered by alveo-lar infection;thus,targeting this axis may represent a novel therapeutic strategy for treating alveo-lar infection-induced liver fibrosis.

Objective:To compare the efficacy and safety of the gastrointestinal endoscopic super minimally invasive surgery (eSMIS) and the laparoscopic minimally invasive procedure (LS) for the treatment of gastric glomus tumors(GGT).Methods:This study retrospectively included 15 patients with GGT who underwent eSMIS at the First Medical Center of Chinese PLA General Hospital from May 2014 to May 2024. Data on demographic characteristics, surgical indexes, efficacy evaluation indexes, postoperative medical disposition, health economics indexes and postoperative laboratory indexes were collected and analyzed, the patients were followed up for survival outcomes and the postoperative quality of life, efficacy and safety of the two groups were compared.Results:The amount of bleeding in the eSMIS group was lower than that in the LS group: 1.25 (0, 3.75) ml vs. 41.56 (10.00, 50.00) ml, and the surgical cost in the eSMIS group was lower than that in the LS group: 10 792.87 (8 424.90, 12 730.30) yuan vs. 21 773.06 (19 940.60, 24 843.10) yuan, there were statistical differences ( P<0.05). The surgical efficacy, postoperative laboratory indicators and medical treatment convenience between the two groups had no statistical differences ( P>0.05). Conclusions:In the choice of surgical procedures for the treatment of GGT, eSMIS is superior to LS in terms of bleeding and surgical cost, and not inferior to LS in other indicators. This suggested that the treatment of GGT with eSMIS is feasible, safe and effective.

Objective:To explore the characteristics of brain functional connectivity changes associated with repetitive transcranial magnetic stimulation (rTMS) in adolescents with anhedonia symptoms, and to develop a predictive model of treatment efficacy based on baseline functional connectivity.Methods:A total of 88 adolescents (aged 13-18 years) with major depressive disorder and comorbid anhedonia, diagnosed according to the Diagnostic And Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), were enrolled in a randomized, double-blind, block-design trial. Participants received either active rTMS ( n=44) or sham stimulation ( n=44) for 15 consecutive days with individualized targeting. Resting-state functional magnetic resonance imaging (fMRI) data and clinical assessments were collected before and after the intervention. Brain regions were parcellated using the Brainnetome Atlas to construct whole-brain functional connectivity matrices. Linear mixed-effects models were used to identify functional connections showing significant group×time interaction effects. The percentage change in Snaith-Hamilton Pleasure Scale (SHAPS) scores (ΔSHAPS) served as the dependent variable in multiple regression analyses to examine the explanatory power of connectivity changes for treatment response. A connectome-based predictive modeling (CPM) approach was employed to predict individual treatment responses based on baseline functional connectivity with permutation testing used to validate model robustness. Results:Thirty-one functional connections showing significant group×time interaction ( F=6.67-15.69, all P<0.01) were identified between the active and sham stimulation groups, primarily involving the subcortical network (SCN), dorsal attention network (DAN), limbic network (LN), and default mode network (DMN). Changes in these connections accounted for 53% of the variance in ΔSHAPS (adjusted R2=0.53, F=4.574, P=0.001). The CPM model based on baseline connectivity showed strong predictive performance (10-fold cross-validation: r=0.65, R2=0.40, MAE=0.095, permutation P<0.001; leave-one-out cross-validation: r=0.74, R2=0.52, MAE=0.013, permutation P<0.001). Among the 59 predictive features, those originating from the LN contributed most substantially, particularly cross-network connections with the DMN and SCN. Correlation analyses revealed widespread associations between baseline predictive features and rTMS-induced connectivity changes, including significant negative correlations between baseline LN-DMN connectivity and post-treatment changes in DAN and subcortical connectivity. Conclusion:rTMS significantly alleviates anhedonia symptoms in adolescents with depression and induces widespread reconfiguration of functional connectivity across multiple brain networks. The CPM model based on baseline connectivity features effectively predicts rTMS treatment efficacy for anhedonia, providing new insights for individualized treatment strategies in adolescent depression.

Objective:To explore the value of intraoperative multimodal monitoring in superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery in evaluating hemodynamic parameters and blood-brain barrier disruption, as well as their correlations with postoperative perfusion changes.Methods:A retrospective case series study was performed; 60 patients with ischemic cerebrovascular diseases admitted to Department of Neurosurgery, Lianyungang Clinical Medical College of Nanjing Medical University (Lianyungang First People's Hospital) from March 2023 to October 2024 were selected, including 17 patients with moyamoya disease and 43 patients with chronic internal carotid artery occlusion and/or chronic symptomatic MCA stenosis/occlusion. All patients were confirmed by CTA or DSA and underwent STA-MCA M4 segment bypass surgery. Intraoperatively, microvascular Doppler ultrasound (MDU), sodium fluorescein angiography, and indocyanine green angiography combined with Flow800 (ICG-Flow800) were used to monitor the blood-brain barrier disruption grade, as well as the peak systolic velocity (PSV) and blood flow direction of the STA and recipient artery before and after arterial anastomosis. Cerebral blood perfusion improvement was reexamined by CT perfusion (CTP) 7 days and 1 month after surgery. These 60 patients were divided into a group with blood flow into the sylvian fissure (inflow group, n=27) and a group with blood flow out of the sylvian fissure (outflow group, n=33) according to the direction of recipient artery blood flow before arterial anastomosis, and further subdivided into subgroups with PSV≤10 cm/s and >10 cm/s based on the recipient artery PSV. Clinical and imaging data of these patients were collected and analyzed as follows: (1) CTP parameters such as cerebral blood volume, cerebral blood flow, mean transit time, and time to peak before surgery, 7 days after surgery, and 1 month after surgery were compared; (2) differences between the recipient artery PSV before arterial anastomosis and recipient artery exiting sylvian fissure velocity (RA.EXV) or recipient artery entering sylvian fissure velocity (RA.ESV) of the recipient artery after anastomosis were compared; (3) differences in ICG-Flow800 fluorescence intensity curve parameters such as delay time, rise time, curve slope, time to peak, and maximum fluorescence intensity of the cerebral surface veins before and after arterial anastomosis were compared; (4) spearman rank correlation was used to analyze the correlation of recipient artery PSV before arterial anastomosis with preoperative CTP parameters in all patients, the correlations of RA.ESV in the inflow group or RA.EXV in the outflow group with CTP parameters 7 days after surgery, and the correlations of blood-brain barrier disruption grade with preoperative CTP parameters, recipient artery PSV before arterial anastomosis, and RA.ESV or RA.EXV after arterial anastomosis in all patients. Results:(1) The blood flow direction of all recipient arteries became bidirectional after surgery. Cerebral blood perfusion improved to varying degrees after surgery: the mean transit time 7 days and 1 month after surgery, and cerebral blood flow 1 month after surgery were significantly higher compared with those before surgery ( P<0.05). (2) Regardless of the blood flow direction (into or out of the sylvian fissure), the RA.ESV or RA.EXV after anastomosis was significantly higher than the recipient artery PSV before anastomosis when the recipient artery PSV≤10 cm/s ( P<0.05). (3) For all patients, the ICG-Flow800 fluorescent intensity curve parameters of cerebral surface veins after anastomosis improved significantly compared with that before anastomosis ( P<0.05). (4) Preoperative recipient artery PSV was positively correlated with preoperative CBF in all patients ( rs=0.445, P=0.020). In the inflow group, postoperative RA.ESV was positively correlated with Tmax 7 days after surgery ( rs=0.490, P=0.009). The blood-brain barrier disruption grade was positively correlated with preoperative Tmax in all patients ( rs=0.478, P=0.012). Conclusion:Intraoperative multimodal monitoring in STA-MCA bypass surgery can provide surgeons with detailed hemodynamic parameters and blood-brain barrier disruption data, enabling real-time evaluation of surgical outcomes to optimize operative decision-making.

Objective:To explore the surgical methods and treatment outcomes of nasal endoscopic surgery for nasal deformity secondary to unilateral cleft lip and palate, combined with nasal septal deviation, using nasal septal cartilage and bone.Methods:Eleven patients who underwent surgical treatment for unilateral cleft lip and palate secondary to nasal deformity in the Department of Otorhinolaryngology, Head and Neck Surgery, Linyi People′s Hospital, Shandong Second Medical University, from March 2021 to March 2023, were retrospectively analyzed. The cohort included 8 males and 3 females, aged (22.0±8.4) years (range: 17 to 35 years). Preoperatively, all of them underwent CT scanning and three-dimensional reconstruction of the nasal bones and sinuses to evaluate the size of the nasal septal cartilage and the design of the material to be taken, and to assess the degree of nasal deformity. During the operation, an open “V”-shaped incision was made through the nasal columella, and part of the septal bone and cartilage were removed under direct nasal endoscopic visualization. The septal cartilage and bony structures were used to correct the nasal deformity, and a nasal brace was used as an intraoperative support for the reconstruction of the nasal cartilage, which was then worn for 1 month after the operation to maintain a stable nasal shape. A visual analog scale (VAS) was used before and after surgery to assess the patient′s satisfaction with the nasal shape and the degree of nasal ventilation. Corresponding data on both sides of the external nose were measured, including nasal tip height, nostril height, nostril width, nasal base width, and nasal columella inclination, to assess the symmetry of the external nose objectively. SPSS 22.0 software was used for statistical analysis to evaluate the surgical results.Results:The surgical incisions of all 11 patients healed at stage Ⅰ. At 6-24 months of postoperative follow-up, nasal symmetry was restored, and the nostrils were equal in size. The difference in symmetry indexes before and after the surgery was statistically significant. The t value for nasal tip height, the nostril height, the nostril width, the nasal base width, and the nasal columellar inclination were 4.21, 2.26, 3.38, 3.65, and 2.36, respectively (all P<0.05). Postoperative incision scarring was not obvious, and patients were satisfied with the nasal appearance [VAS score (9.14±0.48) points vs (3.45±1.23) points, t=14.29, P<0.001], and nasal ventilation was significantly improved [VAS score (9.32±1.24) points vs (4.61±0.85) points, t=10.39, P<0.001]. Conclusion:Nasal endoscopic surgery using septal cartilage and bone to treat nasal deformity secondary to unilateral cleft lip and palate, combined with deviated septum, can simultaneously improve the patients′ nasal shape and nasal ventilation, yielding good clinical outcomes.