ObjectiveTo investigate the mechanism underlying the weight loss effect of electrothermal acupuncture （ETA） in diet-induced obese （DIO） model mice based on the hypoxia-inducible factor-1α （HIF-1α）/sphingosine-1-phosphate （S1P）sphingosine-1-phosphate receptor 3 （S1PR3） signaling pathway-mediated macrophage polarization. MethodsAn obesity mouse model was established by continuously feeding at a high-fat diet （HFD） for 8 weeks. Twenty successfully modeled obese mice were randomly divided into a model group and an electrothermal acupuncture （ETA） group with 10 mice per group， both of which continued to receive the HFD till week 12. Another 10 mice were assigned to the normal group and fed a standard chow diet continuously for 12 weeks. Starting from week 9 of the experiment， mice in the ETA group received electrothermal acupuncture stimulation at Zhongwan （CV12）， bilateral Tianshu （ST25）， and bilateral Zusanli （ST36） for 30 minutes per session， with the instrument current set at （40±0.5）mA and a constant temperature of （40±0.5）℃. Mice in the normal group and the model group were restrained in the same manner for 30 minutes without acupuncture. All interventions were performed once every other day for a total of 4 weeks. Ten hours after the final intervention， the body weight， waist circumference， and body length of mice in each group were measured， and Lee's index was calculated. Serum biochemical analysis was performed to assess fasting blood glucose （FBG）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， blood urea nitrogen （BUN）， and creatinine （Cr）. Serum leptin （LEP） and adiponectin （ADPN） levels， as well as sphingosine-1-phosphate （S1P） levels in epididymal white adipose tissue （eWAT）， were detected by ELISA. Histomorphological changes in eWAT were monitored via HE staining. Flow cytometry was used to analyze macrophage subtype-related indexes in eWAT， including the total proportion of macrophages， the proportion of M1 macrophages， the proportion of M2 macrophages， and the M1/M2 ratio. Antibody array technology was used to determine the levels of differentially expressed inflammatory factors in eWAT between the model and blank groups， as well as between the ETA and model groups. Western blot and qPCR were used to detect the protein and mRNA expression levels of HIF-1α and S1PR3 in the eWAT， respectively. ResultsCompared to the normal group， the model group showed significantly increased body weight， Lee's index， waist circumference， and FBG， TC， TG， HDL-C， LDL-C， AST， and ALT levels， upgraded LEP and S1P levels， decreased ADPN level and ADPN/LEP ratio， elevated proportion of M1 macrophages and the M1/M2 ratio， reduced proportion of M2 macrophages， and upregulated protein and mRNA expression levels of HIF-1α and S1PR3 （P＜0.05 or P＜0.01）. With the exception of HDL-C， all the abovementioned indicators in the ETA group were significantly improved compared to the model group （P＜0.05 or P＜0.01）. Analysis of differentially expressed inflammatory cytokines revealed that， compared to the normal group， the levels of interleukin-1β （IL-1β）， interferon-γ （IFN-γ）， interleukin-6 （IL-6）， and interleukin-12p70 （IL-12p70） in the eWAT of the model group were elevated； conversely， the levels of interleukin-17 （IL-17）， interleukin-5 （IL-5）， IL-6， and interleukin-23 （IL-23） in the eWAT of the ETA group decreased compared to the model group （P＜0.05 or P＜0.01）. ConclusionETA exerts a weight-reducing effect in obese model mice， and the mechanism may involve inhibition of the HIF-1α/S1P/S1PR3 signaling pathway activation， which shifts macrophage polarization from the M1 to M2 phenotype， thereby alleviating chronic inflammation.

ObjectiveTo explore the mechanism of Shouhui Tongbian capsules in treating constipation based on the research foundation of its active components combined with network pharmacology and animal experiments. MethodsThe drug components were imported into SwissTargetPrediction to predict the targets of Shouhui Tongbian capsules， and constipation-related targets were collected from disease databases. A protein-protein interaction （PPI） network was constructed for the common targets shared by Shouhui Tongbian capsules and constipation to screen key targets， which was followed by gene ontology （GO） function and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analyses. A "bioactive component-target-pathway" network was constructed， and the core components of Shouhui Tongbian capsules in treating constipation were screened based on the topological parameters of this network. Molecular docking was employed to predict the binding affinity of core components to key targets. A mouse model of constipation was constructed to screen the key pathways and targets of the drug intervention in constipation. ResultsThe PPI network revealed six key constipation-related targets： protein kinase B （Akt1）， B-cell lymphoma-2 （Bcl-2）， glycogen synthase kinase-3β （GSK-3β）， cyclooxygenase-2 （PTGS2）， estrogen receptor 1 （ESR1）， and epidermal growth factor receptor （EGFR）. The KEGG pathway analysis showed that the phosphatidylinositol 3-kinase （PI3K）/Akt signaling pathway was the most enriched. The topological parameter analysis of the "bioactive component-target-pathway" network screened out the top 10 core components： auranetin， isosinensetin， naringin， diosmetin， quercetin， apigenin， luteolin， hesperidin， isorhapontigenin， and chrysophanol. Molecular docking results showed that the 10 core components had strong binding affinity with the 6 key targets. Animal experiments showed that after intervention with different doses of Shouhui Tongbian capsules， the time to the first black stool excretion was reduced and the fecal water content and small intestine charcoal propulsion rate of mice were improved. After treatment with Shouhui Tongbian capsules， the colonic mucosal injury and glandular arrangement were alleviated， and the muscle layer thickness was increased. Western blot results showed that Shouhui Tongbian capsules recovered the expression of apoptosis-related molecules mediated by the PI3K/Akt pathway in the colonic tissue of constipated mice. Terminal-deoxynucleotidyl transferase-mediated nick end labeling （TUNEL） results showed that the cell apoptosis rate of the colon significantly reduced after intervention with Shouhui Tongbian capsules. ConclusionThe results of network pharmacology and animal experiments confirmed that Shouhui Tongbian capsules can treat constipation through multiple targets and pathways. The capsules can effectively intervene in loperamide-induced constipation in mice by regulating the constipation indicators and reducing cell apoptosis in the colon tissue via activating the PI3K/Akt signaling pathway.

Objective To investigate the relationship between serum microRNA(miRNA,miR)-9-5p,miR-21-5p and miR-206 and hemorrhagic transformation(HT)occurs and prognosis in patients with large ar-tery atherosclerotic cerebral infarction(ACI-LAA)after thrombolysis.Methods A total of 265 patients with ACI-LAA admitted to the hospital from April 2021 to November 2023 were selected as the research objects.According to whether HT occurred after intravenous thrombolysis,they were divided into non-HT group and HT group,and the expression levels of serum miR-9-5p,miR-21-5p and miR-206 were compared between the two groups.The general data of patients with ACI-LAA were collected.Univariate and multivariate Logistic regression analysis were used to analyze the influencing factors of HT occurs in patients with ACI-LAA after thrombolysis.The receiver operating characteristic(ROC)curve was used to analyze the efficacy of serum miR-9-5p,miR-21-5p and miR-206 expression levels in predicting HT occurs after thrombolysis in patients with ACI-LAA.The patients with ACI-LAA were followed up for 90 d.According to the modified Rankin scale(mRS)score,the patients were divided into a good prognosis group and a poor prognosis group,and the expression levels of serum miR-9-5p,miR-21-5p and miR-206 were compared between the two groups.Univa-riate and multivariate Logistic regression analysis were used to analyze the influencing factors of poor progno-sis in patients with ACI-LAA.ROC curve was used to analyze the efficacy of serum miR-9-5p,miR-21-5p and miR-206 expression levels in predicting poor prognosis of patients with ACI-LAA.Results HT occurred in 74(27.92％)of 265 patients with ACI-LAA after thrombolysis.Compared with the non-HT group,the National Institutes of Health Stroke Scale(NIHSS)score atadmission,the proportion of hypertension,the proportion of infarct size ≥10 cm2,and the expression levels of serum miR-21-5p and miR-206 were significantly in-creased in the HT group(P＜0.05).However,the expression level of serum miR-9-5p was decreased(P＜0.05).Hypertension,high NIHSS score at admission,the proportion of infarct size ≥10 cm2,high expression of miR-21-5p and miR-206 were risk factors for HT occurs in patients with ACI-LAA after intravenous thrombolysis,and high expression of miR-9-5p was a protective factor(P＜0.05).The ROC curve showed that the area under the curve(AUC)and 95％CI of single and combined detection of serum miR-9-5p,miR-21-5p and miR-206 for predicting HT occurs were 0.796(0.726-0.866),0.779(0.711-0.846),0.784(0.714-0.854),0.891(0.839-0.943),respectively.Among 265 patients with ACI-LAA,83 patients(31.32％)had poor prognosis at 90 d of follow-up.Compared with the good prognosis group,the age,NIHSS score at admis-sion,the proportion of HT,the proportion of infarct size ≥10 cm2,and the expression levels of serum miR-21-5p and miR-206 were increased(P＜0.05),and the expression level of serum miR-9-5p was decreased(P＜0.05)in the poor prognosis group.Advanced age,high NIHSS score at admission,HT,infarct size ≥10 cm2,high expression of miR-21-5p,and high expression of miR-206 were risk factors for poor prognosis of ACI-LAA patients,and high expression of miR-9-5p was a protective factor(P＜0.05).The ROC curve showed that The AUC(95％CI)of single and combined detection of serum miR-9-5p,miR-21-5p and miR-206 for predicting poor prognosis were 0.754(0.691-0.818),0.779(0.719-0.838),0.792(0.815-0.919),0.931(0.902-0.960),respectively.Conclusion Low expression of serum miR-9-5p,high expression of miR-21-5p and high expression of miR-206 are associated with the HT occurs and poor prognosis in patients with ACI-LAA after thrombolysis,and the combined detection of the three indicators has a high predictive value for the HT occurs and poor prognosis.

Migraine is a complex neurological disorder with unknown etiology,involving genetic and environmental factors.The pathogenesis of migraine is closely related to the activation of microglia and inflammatory factors.ATP is a ligand for the P2X receptor(P2XR),a ligand gated ion channel(LGIC)widely expressed in neurons and gli-al cells.This review elucidates that P2X(P2X3,P2X4,P2X7)receptors regulate the activation of microglia and release of inflammatory factors through different signaling pathways,mediating neuropathic pain and migraine occur-rence,providing potential targets for the treatment of migraine.

Objective:To evaluate the accuracy of L-shaped reduction malarplasty under the guidance of virtual surgical planning (VSP).Methods:The data of adult female patients who were diagnosed with zygomatic protrusion or hypertrophy at Department of Orthognathic and Temporo-mandibular Joint Surgery, West China Hospital of Stomatology, Sichuan University, from January 2018 to December 2020 were analyzed retrospectively. L-shaped reduction malarplasty with or without bone resection and with the mortice and tenon joint structure on the zygomatic arch was conducted either by digital procedures comprising VSP and three-dimensional printing titanium templates (digtal surgery group) or by conventional method (control group). The incidence of postoperative complications and the patient postoperative satisfaction [using a Likert scale with a score ranging from 1 to 5, representing very dissatisfied, dissatisfied, average, satisfied and very satisfied, satisfaction rate = (very satisfied + satisfied)/ total number of patients × 100%] were statistically analyzed in the two groups. The differences in the postoperative symmetry of the zygomatic complex between the digital group and the control group were analyzed by three-dimensional cephalometry. The accuracy of VSP in L-shaped reduction malarplasty was evaluated by comparing the preoperative design model with the actual postoperative model in the digital group. The statistical analyses were conducted using SPSS 24.0 software. The chi-square test was used in the comparison of surgical complications and patient satisfaction rates. The symmetry of bilateral landmarks in the three-dimensional direction between the two groups was evaluated using the independent t-test, and the pre- and post-operative measurements in the digital group were compared using paired t-test. Results:A total of 78 patients were included, with 36 in the digital group, aged (25.2±3.6) years, and 42 in the control group, aged (24.3±2.8) years. Satisfactory reduction of zygomatic protrusion or hypertrophy was recognized among all patients. Compared with the control group, the digital group had lower percentage of complications [25% (9/36) vs. 55% (23/42)] and higher postoperative satisfaction [78% (28/36) vs. 48% (20/42)], both of which were statistically significant (all P<0.01). Regarding the symmetry of bilateral zygomatic complexes, the average deviations of ΔZb (bottom point of zygoma) in the digital group in the horizontal, vertical, and sagittal directions [(1.05±0.24), (1.05±0.24), (1.00±0.88) mm] were significantly smaller than those in the control group [(2.03±0.58), (1.32±0.68), (1.47±0.47) mm], with statistically significant differences (all P<0.05). The bone segment movements of virtual plans and actual result in the digital surgery group were measured and showed no obvious difference for the inward movement [(5.42±0.98) mm vs. (5.33±0.93) mm] and the sagittal overlap [(4.87±1.21) mm vs. (4.77±1.32) mm] at the zygoma roots, along with the step length at the long-arm of the L-shaped osteotomy line [(2.43±1.11) mm vs. (2.39±0.89) mm] (all P>0.05). The mean differences of facial width and protrusion measurements between virtual simulations and actual result in the digital group ranged from (1.13±0.47) mm to (2.07±0.88) mm, with no significant differences( P>0.05). Meanwhile, the high resemblance between virtual plans and actual result was depicted via superimposition models, with a deviation controlled within ±0.5 mm. Conclusion:The application of VSP in reduction malarplasty significantly improved surgical accuracy and reduced difficulties in the operation, which would improve patients’ postoperative satisfaction.

Objective:To explore the clinical application value of MRI ultra-short echo time sequence (MRI-UTE) in the diagnosis of pulmonary nodules.Methods:This study was a cross-sectional study. A total of 101 consecutive patients were recruited prospectively from January to August 2024 at Huazhong Fuwai Hospital of Zhengzhou University. All of the included patients were diagnosed with pulmonary nodules by chest CT examination and intended for treatment. All patients underwent low-dose CT examination and MRI-UTE examination. The number, classification, and lung imaging reporting and data system (lung-RADS) grading of the pulmonary nodules were analyzed. Nodules classification was determined as solid nodules or sub-solid nodules, and sub-solid nodules included part-solid nodules and pure ground-glass nodules. Taking the evaluation results of radiologists with 10 and 12 years of experience in chest imaging diagnosis as the reference standard, the Kappa test was used to analyze the agreement of CT and MRI-UTE in terms of the accurate diagnosis, classification, and lung-RADS grading of pulmonary nodules. Results:Among the 101 patients, a total of 216 pulmonary nodules were identified. MRI-UTE accurately diagnosed 180 pulmonary nodules, while 203 pulmonary nodules were detected by CT. The concordance was moderate ( Kappa=0.48, P<0.001). In terms of nodule classification, CT correctly classified 167 nodules as solid and 36 as sub-solid, whereas MRI-UTE correctly classified 153 as solid and 23 as sub-solid, with good agreement (weighted Kappa=0.73, P<0.001). For lung-RADS grading, CT correctly graded 186 nodules, with 85 graded as category 2, 46 as category 3, 33 as category 4A, 12 as category 4B, and 10 as category 4X; MRI-UTE correctly graded 155 nodules, with 74 graded as category 2, 30 as category 3, 30 as category 4A, 12 as category 4B, and 9 as category 4X. The agreement between the two modalities in determining lung-RADS grade was also good (weighted Kappa=0.74, P<0.001). Conclusion:MRI-UTE demonstrates good agreement with CT in the accurate diagnosis, classification, and lung-RADS grading of pulmonary nodules, indicating certain clinical application value.

Objective:the subclavian approach without insufflation, the ability of assistants to master the technique of holding the endoscope plays a crucial role in the thoroughness and smoothness of the surgery. The author has summarized the "six-marker method", which adjusts the mirror holding technique based on surgical steps and surgical operation goals, so that assistants can quickly grasp the essentials of mirror holding and assist the chief surgeon in completing the surgery smoothly. This method has wide applicability and feasibility, which can achieve good coordination between the surgeon and the mirror holder, shorten the surgical time and break in period. It is worth promoting and applying in clinical practice.

Tracheal intubation in emergency and complex scenarios is difficult for critical care medicine residents.Virtual reality(VR)technology has not been used in the training of tracheal intubation in critical care scenarios in China.This project team has developed an emergency tracheal intubation training system for the intensive care unit(ICU)based on virtual simulation technology,and has obtained the computer software copyright registration certificate from the National Copyright Administration(registration number:2024SR1139484).This system uses a case script of acute respiratory distress syndrome(ARDS)secondary to severe acute pancreatitis,sets the roles of patients,family members,nurses and residents,collects digital resources of ICU rescue scenes,computer-aided design(CAD)drawings,instrument models and equipment photos,models instruments and equipment,and uses PICO 4 Pro VR helmets to display the ICU environment in the virtual scene.The key points of skill assessment include tracheal intubation operation,the ability to interpret laboratory results,the ability to judge diseases and the ability to work in teams.The user center contains 3 submodules,namely,the score center,skill analysis and user management.There are 3 user roles in the system,namely,residents,teachers and administrators.The system can track and record the entire operation process,including video recording and playback,and score and comprehensively evaluate each step,thereby realizing an objective and quantitative training and assessment system.By simulating the three-dimensional clinical operation environment of the ICU,the entire process of real tracheal intubation is fully reproduced.Resident doctors are placed in the ICU rescue scene,focusing on training tracheal intubation skills,the ability of doctor-patient communication,on-the-spot response,and teamwork,which is expected to become an important type of standardized teaching in critical care medicine.

Objective:To explore the relationship between anxiety status and progestogen level in perimenopausal women and their effects on the pathogenesis of uterine fibroid.Methods:A total of 376 perimenopausal women who visited the Department of Gynecology and Neurology of Nanjing Tongren Hospital affiliated School of Medicine of Southeast University from August 2019 to July 2023 were selected as the study subjects.Based on the and divided into two groups according to the Self-Rating Anxiety Scale(SAS),they were divided into a non-anxiety group(n=202,SAS score<50)and an anxiety group(n=174,SAS score≥50).Additionally,according to the presence or absence of uterine fibroids,they were categorized into a non-uterine fibroid group(n=225)and a uterine fibroid group(n=151).The t test or x2 test was used to compare general demographic and clinical data between the non-uterine fibroid group and the uterine fibroid group.Multivariate logistic regression analysis was used to analyze the correlation between anxiety status,progesterone level,and uterine fibroid risk in perimenopausal women.The bootstrap method was used to analyze whether progesterone level mediate the relationship between anxiety status and uterine fibroid risk.Results:Comparison of baseline data between the non-uterine fibroid group and the uterine fibroid group showed that previous caesarean section,number of abortions,hemoglobin level,neutrophil count,lymphocyte count,and neutrophil-to-lymphocyte ratio(NLR)were not associated with the incidence of uterine fibroid(all P>0.05).In contrast,menstrual period,menstrual cycle,progesterone level,and SAS score were significantly associated with the incidence of uterine fibroid(all P<0.05).Analysis of the effects of different clinical features on the risk of uterine fibroid showed that age,chronic diseases history,and dysmenorrhea history were all significantly associated with the incidence of uterine fibroid in perimenopausal women(all P<0.05).Further,univariate logistic regression analysis showed that age≥55 years,chronic diseases,and dysmenorrhea were significant risk factors for uterine fibroid in perimenopausal women(all P<0.05).These seven significant risk factors(menstrual period,menstrual cycle,progesterone level,SAS score,age,chronic disease history,and dysmenorrhea history)were included in a multivariate logistic regression analysis,which identified SAS score and progesterone level as independent risk factors for uterine fibroid in perimenopausal women.Specifically,SAS score was positively correlated with uterine fibroid risk,while progesterone level was negatively correlated with the risk.Restriction cubic spline analysis showed a nonlinear quantitative response relationship between continuously changing progesterone level and the risk of uterine fibroid(x2=12.315,P<0.001),when progesterone level was≤2.00 ng/mL,the risk of uterine fibroid decreased with the increase of progesterone level(HR=1.014,95%CI:1.006-1.012,P<0.001),and when progesterone level was>2.00 ng/mL,the risk of uterine fibroid stabilized with further increases in progesterone level(HR=1.003,95%CI:0.998-1.002,P=0.001).After further adjusting for a variety of related confounding factors affecting the incidence of uterine fibroid in perimenopausal women,it was found that SAS score was an independent risk factor for predicting the incidence of uterine fibroid in perimenopausal women.Mediation effect analysis revealed that SAS score had a direct effect on the incidence of uterine fibroid(β1=0.202,95%CI:0.124-0.216),and progesterone level partially mediated the effect of SAS score on uterine fibroid risk(β2=0.196,95%CI:0.152-0.207).The total effect value was βtotal=0.398,and the mediating effect accounted for 49.25%of the total effect.Conclusion:There was an independent correlation between anxiety status and progestogen level in perimenopausal women,anxiety status was a risk factor for the development of uterine fibroids,while progestogen levelwas a protective factor.

A novel analytical method was developed in this study by combining online solid phase extraction with ultra performance liquid chromatography-tandem mass spectrometry(Online SPE-UPLC-MS/MS)for simultaneous determination of 50 kinds of steroid hormones in surface water.Specifically,after high-speed centrifugation of 4 mL water samples,the supernatant was directly injected into an Oasis HLB online SPE column for enrichment and purification.Subsequently,the target compounds were transferred to the analytical column via valve switching for separation and analysis.The chromatographic separation was performed on a Thermo Acclaim RSLC C18 column(100 mm×2.1 mm,2.2 μm),using a mobile phase composed of 5 mmol/L ammonium fluoride aqueous solution and acetonitrile.Mass spectrometric detection was conducted in positive ion mode,utilizing multiple reaction monitoring(MRM)with quantification achieved by the internal standard method.The method validation demonstrated that the limits of detection(LOD)for the 50 kinds of steroid hormones ranged from 0.02 to 0.50 ng/L,while the limits of quantification(LOQ)were between 0.08 and 1.67 ng/L.The average recoveries in surface water samples at spiked concentrations of 5,20 and 200 ng/L were between 74.1％and 119％,with relative standard deviations(RSDs)of 0.2％to 9.9％.This method was applied to analyze 11 surface water samples collected from sites surrounding a pharmaceutical and chemical industrial park.A total of 44 kinds of steroid hormones were detected,with concentrations ranging from 0.11 to 88.6 ng/L,revealing the presence of hormone contamination in the environmental waters surrounding industrial areas.Compared with the traditional offline SPE methods,the proposed online SPE technique significantly reduced sample volume requirements and pretreatment time,while minimizing the loss of target compounds during the pretreatment process.Moreover,compared to reported online SPE techniques,this method achieved high-throughput analysis of multiple classes of steroid hormones,with lower detection limits and higher recoveries.Overall,this method provided rapid sample preparation,high sensitivity,and excellent stability,making it suitable for the direct analysis of trace steroid hormones in surface water.