Objective To explore the effect of myotubularin-related protein 6(MTMR6)on the invasion of hepatocellular carcinoma cell line HepG2 and the potential molecular mechanism.Methods By analyzing the sequencing results of liver cancer tissues and adjacent tissues in Gene Expression Omnibus(GEO)database,MTMR6 gene was screened out,and Spearman analysis was used to analyze the correlation of MTMR6 and pathway in the Cancer Genome Atlas(TCGA)database.Finally,the interaction between MTMR6 and signaling pathway proteins was analyzed with Genemania database.Then the expression of MTMR6 in human normal liver cell line LO-2 and hepatoma cell lines Huh-7 and HepG2 were measured and compared among the cell lines.Then HepG2 cells was selected as the study object.After MTMR6 gene was knocked down or over-expressed in HepG2 cells,Transwell assay was employed to observe invasion ability,and Western blotting was adopted to detect the expression of MTMR6,PI3K,p-PI3K,AKT,p-AKT,mTOR,p-mTOR MMP-2 and MMP-9.Results The expression of MTMR6 was significantly higher in the hepatocellular carcinoma tissues than the paracancer tissues,and it was in a positive linear correlation with PI3K/AKT/mTOR signaling pathway(P＜0.01),showing interaction with PI3K,AKT and mTOR.The expression level of MTMR6 was significantly higher in the HepG2 cells than the LO-2 and Huh-7 cells(P＜0.01).Over-expression of MTMR6 obviously enhanced invasion ability(P＜0.01),while its knockdown decreased the ability(P＜0.01)in HepG2 cells.Knockdown of MTMR6 gene also resulted in decreased phosphorylation of PI3K,AKT and mTOR,and expression levels of MMP-2 and MMP-9(P＜0.01),while over-expression of MTMR6 promoted the phosphorylation of PI3K,AKT and mTOR,and up-regulated the expression of MMP-2 and MMP-9(P＜0.01).In addition,LY294002(a specific PI3K inhibitor)treatment could block the PI3K/AKT/mTOR pathway and down-regulate the expression of MMP-2 and MMP-9(P＜0.01),but had no effect on MTMR6 expression.Conclusion MTMR6 may promote the invasion of hepatoma cells through activation of PI3K/AKT/mTOR signaling pathway.

Objective: To investigate the screening results of adolescent scoliosis in Chuzhou City, Anhui Province, and analyze the influencing factors for scoliosis, so as to provide insights into the prevention and control of scoliosis among adolescents. Methods: Students were selected from six primary and middle schools in Chuzhou City using the stratified random cluster sampling method from April to June 2023. Demographic information, daily behaviors and postures, and exercise status were collected through questionnaire surveys. Scoliosis was screened and diagnosed according to the Screening for Abnormal Spinal Curvature in Children and Adolescents. Influencing factors for scoliosis among primary and middle school students were identified using a multivariable logistic regression model. Results: A total of 1 823 questionnaires were allocated, and 1 768 effective questionnaires were recovered, with an effective response rate of 96.98%. There were 537 primary school students, 1 000 junior high school students and 231 senior high school students, with an average age of (13.40±1.92) years. There were 948 male students (53.62%) and 820 female students (46.38%). A total of 131 cases of scoliosis were screened positive, with a positive rate of 7.41%. The results of multivariable logistic regression analysis showed that gender (female, OR=1.759, 95%CI: 1.135-2.727), body mass index (OR=0.593, 95%CI: 0.538-0.654), sleeping position (side lying, OR=0.598, 95%CI: 0.377-0.951; prone lying, OR=2.336, 95%CI: 1.201-4.545), frequency of reading in bed (often, OR=2.099, 95%CI: 1.201-3.670), way of carrying backpack (shoulders, OR=0.580, 95%CI: 0.370-0.908), and exercise level (OR=0.428, 95%CI: 0.296-0.618) were influencing factors of scoliosis among primary and middle school students. Conclusion The positive rate of scoliosis screening among primary and middle school students in Chuzhou City was 7.41%, which was influenced by gender, age, body mass index, sleeping posture, reading in bed, way of carrying backpack and exercise level.

ObjectiveTo establish a neuroinflammation-based obesity and depression comorbidity （COM） model in mice and explore the pharmacodynamics and preliminary pharmacological mechanism of tripterine on COM mice. MethodC57BL/6J mice were randomly divided into a normal group （Chow）， a diet-induced obesity group （DIO）， and a COM group. The mice in the COM group were fed on a high-fat diet and chronically stressed with moist litter for 12 weeks to establish the COM model. C57BL/6J mice were randomly divided into a Chow group， a COM group， and a tumor necrosis factor-α（TNF-α） knock-down group. In the TNF-α knock-down group， TNF-α shRNA adeno-associated virus was injected into the amygdala through brain stereotaxis， and the expression of TNF-α in the amygdala was down-regulated. C57BL/6J mice were randomly divided into a Chow group， a DIO group， a DIO + low-dose tripterine group （0.5 mg·kg^-1）， a DIO + high-dose tripterine group （1.0 mg·kg^-1）， a COM group， a COM + low-dose tripterine group （0.5 mg·kg^-1）， and a COM + high-dose tripterine group （1.0 mg·kg^-1）. The body weight， food intake， glucose tolerance， white/brown fat ratio， serum total cholesterol （TC）， triglyceride （TG）， and high-/low-density lipoprotein cholesterol （HDL-C and LDL-C） content were recorded， and obesity of mice in each group was evaluated. Forced swimming test （FST）， tail suspension test （TST）， and open field test were used to evaluate the degree of depression of mice in each group. Immunofluorescence staining was used to detect the protein expression levels of neuropeptide Y， tryptophan hydroxylase 2 （TPH2）， and brain-derived neurotrophic factor （BDNF） in various brain nuclei of mice. Correlation analysis was used to detect the correlation of obesity and depression indexes. ResultThe comparison of the Chow group and the DIO group indicated that COM mice showed obesity and depression. To be specific， obesity was manifested as increased body weight and food intake （P<0.05， P<0.01）， as well as increased NPY expression in the central amygdala， and depression was manifested as prolonged immobility time in FST and TST （P<0.01）， and reduced TPH2-positive 5-hydroxytryptamine neurons in the dorsal raphe nucleus （DRN） and basolateral nucleus of the amygdala （BLA）. The down-regulation of TNF-α protein in BLA of COM mice shortened the immobility time in FST and TST （P<0.05， P<0.01）， increased TPH2/BDNF-positive neurons in BLA， and showed no significant changes in obesity. In DIO mice， the administration of 0.5 mg·kg^-1 tripterine for 9 days significantly decreased the 60 min blood glucose in glucose tolerance （P<0.01） and food intake （P<0.05）. In COM mice， 1.0 mg·kg^-1 tripterine was administered for 14 days to significantly decrease 30 min blood glucose in glucose tolerance （P<0.01）， and food intake （P<0.05）， and immobility time in TST （P<0.01）， increase TPH2-BDNF double-labeled cells in BLA and DRN， and reduce the area of TMEM119-stained cells. ConclusionThe model of obesity and depression comorbidity can be properly induced in mice under the condition of dual stress of energy environment. Tripterine can effectively interfere with obesity-depression comorbidity， and its mechanism may be related to the inhibition of central nervous system inflammation.

Background Hand-arm vibration disease is harmful to human body, but there are no effective diagnosis and treatment so far, and current occupational exposure limits underestimate the health damage caused by high-frequency vibration exposure. Objective To evaluate and compare the damage to workers' peripheral circulation and peripheral nerve caused by different frequencies of vibration operation. Methods Drilling workers (n=187) from a mining company in Shandong Province and golf club head grinding workers (n=228) from a sports equipment factory in Guangdong Province were selected as study subjects. Hand symptoms were investigated. SV106 vibration meter was used to measure the target operation-associated vibration frequency spectrum. The 8 h energy-equivalent frequency weighted acceleration, cumulative vibration exposure level (CVEL), and the working age related to causing white finger in 10% of an exposed group were calculated. Result The study subjects were all male. More grinding workers reported hand symptoms than the drilling workers, e.g. peripheral circulation injury (52.6% vs 19.3%), peripheral nerve injury (71.5% vs 23.0%), hand stiffness (64.0% vs 7.0%), and deformed fingers (69.7% vs 4.3%) (all P<0.001). The main vibration frequencies of grinding operation (500-800 Hz) were much higher than those of drilling operation (125~160 Hz). CVEL and working age of vibration exposure showed a linear rising relationship with the cumulative prevalence rate of peripheral circulation and peripheral never injury, the fitting lines all showed good fitting effects (R²=0.812-0.988), and the slope of the fitting line of the grinding workers was larger than that of the drilling workers. The working age of vibration exposure associated with 10% cumulative prevalence of white finger was shorter in the grinding workers than in the drilling workers (6.81 years vs 10.27 years). According to the ISO prediction formula, the working age of vibration exposure was associated with 10% white finger prevalence shorter in the drilling workers than in the grinding workers (3.12 years vs 8.23 years). Conclusion Both the vibration exposure level and the prevalence of hand symptoms are high in two groups of workers with different vibration frequencies, and vibration exposure at a higher frequency tends to have severer damage to workers' hands.

Background Long-term exposure to hand-transmitted vibration can lead to hand-arm vibration syndrome, one manifestation of which is impaired peripheral blood circulation in the arms. Altered expressions of prostacyclin I₂ (PGI₂) and thromboxane A₂ (TXA₂) in blood may be one of the important mechanisms of vibration-induced hand-arm vibration syndrome. Objective To reveal the effects of rat tail vibration on the expressions of PGI₂ and TXA₂ in plasma, and to establish the correlation between the change of rat plasma PGI₂ to TXA₂ ratio and rat tail vibration. Methods Fifty SPF-grade male SD rats were randomly divided into five groups: control group, 1 d exposure group, 3 d exposure group, 7 d exposure group, and 14 d exposure group, with 10 rats in each group. The rats were placed in rat immobilizes on a immobilization table, and the rats' tails were connected to a shaker and fixed with medical tape. There was no overlap between the immobilizes and between the rats' tails by no contact between the immobilization table and the shaker. The exposure dose was 125 Hz, 5.9 m·s⁻², 4 h·d⁻¹, and the vibration direction was linear vertical vibration. Abdominal aortic blood was taken at the end of vibration exposure, and the expressions of PGI₂, TXA₂, and their hydrolysates 6-keto-prostaglandin F_1α (6-keto-PGF_1α) and thromboxane B₂ (TXB₂) were measured by enzyme-linked immunosorbent assay, and the 6-keto-PGF_1α/TXB₂ values were calculated. Spearman rank correlation was used to analyze whether the expression of vascular factors correlated with the accumulated time of vibration. Results The expression levels of plasma 6-keto-PGF_1α were (896.12±124.37), (1068.13±119.41), (1215.26±122.64), and (1317.94±106.54) ng·L⁻¹ in the 1 d, 3 d, 7 d, and 14 d groups of rats, respectively, which were higher than that in the control group, (830.60±109.47) ng·L⁻¹ (P<0.001). The PGI₂ expression levels were (86.49±2.40), (107.90±2.65), (114.02±2.16), and (126.95±1.94) ng·L⁻¹ in the 1 d, 3 d, 7 d, and 14 d groups of rats, respectively, all higher than (60.09±2.11) ng·L⁻¹ in the control group (P＜0.001). The expression levels of TXB₂ were (132.14±4.10), (145.52±4.09), (179.91±4.98), and (204.10±3.22) ng·L⁻¹ in the 1 d, 3 d, 7 d, and 14 d groups of rats, respectively, which were higher than that in the control group, (106.08±3.26) ng·L⁻¹ (P<0.001). The expression levels of plasma TXA₂ were (211.99±3.24), (236.33±3.88), and (245.45±4.23) ng·L⁻¹ in rats in the 3 d, 7 d, and 14 d groups, respectively, which were all elevated compared with (174.79±4.19) ng·L⁻¹ in the control group (P<0.001). Compared with the control group, the 6-keto-PGF_1α/TXB₂ values were decreased in the 7 d and 14 d groups (P<0.05). The 6-keto-PGF_1α, PGI₂, TXB₂, and TXA₂ expressions were positively correlated with vibration accumulation time (r=0.84, 0.84, 0.80, 0.84, P<0.001) and the 6-keto-PGF_1α/TXB₂ values were negatively correlated with vibration accumulation time (r=-0.24, P=0.003). Conclusion Local exposure of rat tail to vibration could increase the expressions of PGI₂ and TXA₂ in blood, and the elevated expressions show a dose-effect relationship with the duration of vibration exposure, but the PGI₂/TXA₂ tends to decrease with the accumulation of vibration exposure.

Background The metabolites and metabolic pathways of hand-arm vibration syndrome have not yet been elucidated. Objective To investigate the effect of local vibration on endogenous metabolites in rat serum by metabolomic analysis, to preliminarily explore the potential metabolic pathway of endogenous metabolites, so as to provide evidence for further research on the mechanism of hand-arm vibration syndrome. Methods Thirty-two SPF male SD rats, (211.3±11.1) g, 7−8 weeks of age, were selected and randomly divided into three groups: control group (14 rats, without vibration), 7 d vibration group (9 rats, continuously vibration for 7 d), and 14 d vibration group (9 rats, continuous vibration for 14 d). The vibration rats were vibrated every day for 4 h, the frequency weighted acceleration was 4.9 m·s⁻², the vibration frequency was 125 Hz, and the vibration direction was one-way vertical vibration. The control group had the same conditions except not contacting vibration. After the vibration exposure, the blood samples taken from the abnormal aorta of rats were collected, and the changes of rat serum metabolome were analyzed by ultra-performance liquid chromatography-tandem time-of-flight mass spectrometry. Principal components analysis (PCA) was used to explore changes in rat serum metabolic profile, and orthogonal partial least squares-discriminant analysis (OPLS-DA) was used to screen out differential metabolites. Combined with online databases, a metabolic pathway enrichment analysis of differential metabolites was performed. Results The PCA analysis showed that compared with the control group, the rat serum metabolic profiles in the 7 d group and the 14 d group were clearly differentiated, and the rat serum metabolic profiles in the 7 d group and the 14 d group partially overlapped. The OPLS-DA analysis showed significant differences between groups. The main parameters were: model interpretation rate R²Y=0.914, model predictive ability Q²=0.58. The OPLS-DA analysis screened out 26 and 119 differential metabolites from the 7 d group and the 14 d group respectively, and there were 24 common differential metabolites between the 7 d group and the 14 d group. The metabolomic pathway analysis showed that local vibration-induced changes in rat serum metabolism were mainly related to arachidonic acid metabolism in the 14 d group, among which the metabolites with significant effects were arachidonic acid, prostaglandin E₂, and prostaglandin D₂. Conclusion Local vibration could affect the normal metabolism in rats, and the metabolic pathway with significant influence is arachidonic acid metabolism after a 14 d exposure and the involved metabolites are arachidonic acid, prostaglandin E₂, and prostaglandin D₂.

The glymphatic system, as "waste" clearance pathway in the brain, plays a critical role in maintaining the homeostasis of the brain cell microenvironment. It has been found that changes in the glymphatic system are common in many neurological diseases. MRI is currently the only technology that can achieve human glymphatic imaging, and has the advantages of high soft tissue resolution and sensitivity to tracers. Quantitative MRI can objectively evaluate the changes of inflow and outflow of glymphatic system. Therefore, in this review, we introduce the application of quantitative MRI technology in the glymphatic system in detail, aiming to provide help for the diagnosis and treatment of diseases related to glymphatic system.

AIM: To explore the promoting effect of 2-APB on skin wound healing in mice and its potential mechanism. METHODS: KM mice were divided into 5 groups: control group, DMSO group, low (50 mg/L), medium (100 mg/L) and high (200 mg/L) concentration 2-APB group. On the back of each mouse's skin use a circular punch about 1 cm on both sides of the midline of the spine to make a skin wound with a diameter of 10 mm and as deep as the fascia. The control group was only wrapped with gauze and no drugs were applied; the DMSO group was applied 1 g DMSO/Vaseline ointment per day; in the 2-APB group, apply 1 g of 2-APB/Vaseline ointment at a corresponding concentration every day. Pictures were taken the next day to observe the healing, and the material was taken on the 21st day, HE staining was used to observe the pathological morphology of the wound and western blot to detect TRPM7, TGF-β, collagen-I and IL-1β expression. RESULTS: Compared with the control group and the DMSO group, different concentrations of 2-APB could significantly promote skin wound healing in mice (P<0.01), but there was no significant difference in wound healing rate between the DMSO group and the control group group. The results of HE staining showed that, compared with the control group group and the DMSO group, 2-APB could increase the collagen content of the wound and the thickness of the dermis (P<0.01), but there was no significant difference between the DMSO group and the control group group. At the same time, 2-APB could also significantly increase the expression of TGF-β and Col-I on the wound, and inhibit the expression of TRPM7 and IL-1β. CONCLUSION: Different concentrations of 2-APB (50, 100 and 200 mg/L) can promote skin wound healing, and its mechanism may be related to the inhibition of TRPM7.

Objective:To analyze the electrophysiological characteristics of subacute combined degeneration of spinal cord in 10 patients with nitrous oxide poisoning.Methods:Ten patients with nitrous oxide poisoning (case group) and 20 controls (control group)treated in Dalian Municipal Central Hospital Affiliated of Dalian Medical University from January 2016 to January 2020 were included in this study. MRI and electrophysiological examinations were performed on the head, cervical spine and thoracic spine, including distal motor latency (DML), motor nerve amplitude (CMAP), motor conduction velocity (MNCV), sensory conduction velocity (SNCV), sensory nerve amplitude (SNAP), N20 latency of upper limb cortical somatosensory evoked potential and P40 latency of lower limb cortical somatosensory evoked potential. The above indexes were compared between the two groups.Results:In the case group, DML of motor nerve was prolonged, MNCV was slowed down, CMAP was decreased, SNCV was slowed down and SNAP was decreased compared with the control group, the differences were statistically significant ( P<0.05). The incubation periods of N20 and P40 in the case group were longer than those in the control group: (32.70 ± 3.34) ms vs. (18.85 ± 1.37) ms, (57.00 ± 4.08) ms vs. (38.40 ± 1.54) ms, the differences were statistically significant ( t = 16.20, 18.20, P<0.01). The inverted "V" type T 2 long signal of cervical spinal cord and thoracic spinal cord could be seen on MRI of cervical or cervical and thoracic vertebrae in 5 patients. Conclusions:Nitrous oxide poisoning can cause obvious subacute combined degeneration of spinal cord, involving peripheral nerve and spinal cord damage. Peripheral nerve damage can involve motor fibers and sensory fibers, mainly axonal damage, accompanied by demyelination damage, especially in both lower limbs.

Objective:To analyze the antigenicity and genetic characteristics of two strains of Eurasian avian H1N1 swine influenza virus (EAS-H1N1) isolated from 2 human cases found in Gansu province to provide scientific reference for disease prevention and control.Methods:Two cases of human infection with EAS-H1N1 discovered in Gansu province since February 2021 were analyzed for antigenicity and genome comparison, and their genome characteristics were analyzed using software such as Mega7.0.Results:Two human infections with EAS-H1N1 had related environmental exposure history. Two strains were obtained: A/Gansu-Xifeng/1143/2021 and A/Gansu-Xifeng/1194/2021. The two strains of HA, NA genes were all from the Eurasian avian H1N1 swine influenza virus, and are closely related to the human infection EAS-H1N1 virus in Hebei and Tianjin and the EAS-H1N1 virus isolated from the mink in Shandong; the HA receptor binding sites of 2 strains E190D and D225E mutations occurred in all spots, and there were no H274Y and N294S mutations in NA protein.Conclusions:Some important molecular mutations occurred in the genome of people infected with EAS-H1N1 virus in Gansu province, which may lead to increased virulence and potential human-to-human transmission. Strengthening the research and analysis of EAS-H1N1 gene characteristics will help to monitor the mutation and mutation of the virus at the molecular level and scientifically prevent and control the epidemic.