N6-methyladenosine(m6A)is the most common mRNA modification in eukaryotes,and fat mass and obesity-related protein(FTO),are its demethylases,which efficiently remove the modification of m6A mRNA,and is strongly associated with obesity.Atherosclerosis is a chronic inflammatory lesion of the blood vessel wall driven by lipids.It was found that FTO-mediated m6A may influence the process of atherosclerosis through lipid metabolism,oxidative stress,mitochondrial dysfunction,and macrophage foaminess.

Objective To investigate the molecular mechanism by which receptor activator of nuclear factor-κB ligand(RANKL)regulates autophagy and osteoclast differentiation through the ROS-HIF-1α signaling axis.Methods Mouse monocytic/macrophage RAW264.7 cells were randomly divided into control group,RANKL group,and 3 combined intervention groups,that is,RANKL+CQ group(intervention with autophagy inhibitor,CQ),RANKL+FG-4592 group(intervention with HIF-1α stabilizer,FG-4592),and RANKL+NAC group(intervention with ROS scavenger,NAC).The number of mature multinucleated osteoclasts was quantitatively detected with tartrate-resistant acid phosphatase(TRAP)staining;the protein levels of HIF-1α and LC3 were detected by Western blotting and the mRNA levels of osteoclast differentiation-related genes(TRAP,Cath K and MMP-9)were analyzed by qRT-PCR;autophagy flux and activity were observed by adenovirus mRFP-GFP-LC3 labeling system combined with confocal laser microscopy;and the production of intracellular reactive oxygen species(ROS)was measured by DCFH-DA probe.Results Compared with the control group,the RANKL group obtained significantly increased number of TRAP-positive multinucleated osteoclasts(P<0.05),up-regulated mRNA levels of osteoclast differentiation-related genes,activated autophagy pathway,as evidenced by the increased LC3-Ⅱ/LC3-Ⅰ ratio(P<0.05)and number of autophagic lysosomes(P<0.05),elevated intracellular ROS generation(P<0.05),and down-regulated HIF-1α protein level(P<0.05).NAC intervention significantly inhibited intracellular ROS accumulation(P<0.05),reversed the lowered expression of HIF-1α protein(P<0.05),decreased the LC3-Ⅱ/LC3-Ⅰ ratio(P<0.05)and autophagy flux and activity(P<0.05),and reduced expression levels of osteoclast differentiation-related genes and the number of mature osteoclasts(P<0.05).In the RANKL+FG-4592 group,HIF-1α protein level was significantly increased(P<0.05),autophagy activation was inhibited[with decreased LC3-Ⅱ/LC3-Ⅰ ratio(P<0.05)and autophagy flux and activity(P<0.05)],and the expression of osteoclast differentiation-related genes and number of mature osteoclasts were decreased(P<0.05)when compared with the RANKL group.While CQ treatment resulted in inhibited autophagy flux and activity(P<0.05),declined expression levels of osteoclast differentiation-related genes,and reduced number of mature osteoclasts(P<0.05).Conclusion RANKL activates autophagy through ROS-mediated down-regulation of HIF-1α,and thereby promotes osteoclast differentiation.

N6-methyladenosine(m6A)is the most common mRNA modification in eukaryotes,and fat mass and obesity-related protein(FTO),are its demethylases,which efficiently remove the modification of m6A mRNA,and is strongly associated with obesity.Atherosclerosis is a chronic inflammatory lesion of the blood vessel wall driven by lipids.It was found that FTO-mediated m6A may influence the process of atherosclerosis through lipid metabolism,oxidative stress,mitochondrial dysfunction,and macrophage foaminess.

Objective To investigate the mechanisms that mediate the neuroprotective effect of the intestinal microbial metabolite sodium butyrate(NaB)in a mouse model of Parkinson's disease(PD)via the gut-brain axis.Methods Thirty-nine 7-week-old male C57BL/6J mice were randomized equally into control group,PD model group,and NaB treatment group.In the latter two groups,PD models were established by intraperitoneal injection of 30 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)once daily for 5 consecutive days,and normal saline was injected in the control group.After modeling,the mice received daily gavage of NaB(300 mg/kg)or an equal volume of saline for 14 days.Behavioral tests were carried out to assess the changes in motor function of the mice,and Western blotting was performed to detect the expressions of tyrosine hydroxylase(TH)and α-synuclein(α-syn)in the striatum and nuclear factor-κB(NF-κB),tumor necrosis factor(TNF-α),interleukin 6(IL-6),and the tight junction proteins ZO-1,Occludin,and Claudinin the colon.HE staining was used to observe inflammatory cell infiltration in the colon of the mice.RNA sequencing analysis was performed to identify the differentially expressed genes in mouse colon tissues,and their expressions were verified using qRT-PCR and Western blotting.Results The mouse models of PD with NaB treatment showed significantly increased movement speed and pulling strength of the limbs with obviously upregulated expressions of TH,Occludin,and Claudin and downregulated expressions of α-syn,NF-κB,TNF-α,and IL-6(all P<0.05).HE staining showed that NaB treatment significantly ameliorated inflammatory cell infiltration in the colon of the PD mice.RNA sequencing suggested that Bmal1 gene probably mediated the neuroprotective effect of NaB in PD mice(P<0.05).Conclusion NaB can improve motor dysfunction,reduce dopaminergic neuron loss in the striatum,and ameliorate colonic inflammation in PD mice possibly through a mechanism involving Bmal1.

Objective To investigate the mechanisms that mediate the neuroprotective effect of the intestinal microbial metabolite sodium butyrate(NaB)in a mouse model of Parkinson's disease(PD)via the gut-brain axis.Methods Thirty-nine 7-week-old male C57BL/6J mice were randomized equally into control group,PD model group,and NaB treatment group.In the latter two groups,PD models were established by intraperitoneal injection of 30 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)once daily for 5 consecutive days,and normal saline was injected in the control group.After modeling,the mice received daily gavage of NaB(300 mg/kg)or an equal volume of saline for 14 days.Behavioral tests were carried out to assess the changes in motor function of the mice,and Western blotting was performed to detect the expressions of tyrosine hydroxylase(TH)and α-synuclein(α-syn)in the striatum and nuclear factor-κB(NF-κB),tumor necrosis factor(TNF-α),interleukin 6(IL-6),and the tight junction proteins ZO-1,Occludin,and Claudinin the colon.HE staining was used to observe inflammatory cell infiltration in the colon of the mice.RNA sequencing analysis was performed to identify the differentially expressed genes in mouse colon tissues,and their expressions were verified using qRT-PCR and Western blotting.Results The mouse models of PD with NaB treatment showed significantly increased movement speed and pulling strength of the limbs with obviously upregulated expressions of TH,Occludin,and Claudin and downregulated expressions of α-syn,NF-κB,TNF-α,and IL-6(all P<0.05).HE staining showed that NaB treatment significantly ameliorated inflammatory cell infiltration in the colon of the PD mice.RNA sequencing suggested that Bmal1 gene probably mediated the neuroprotective effect of NaB in PD mice(P<0.05).Conclusion NaB can improve motor dysfunction,reduce dopaminergic neuron loss in the striatum,and ameliorate colonic inflammation in PD mice possibly through a mechanism involving Bmal1.

Objective To explore clinical outcomes of extracorporeal shock wave and therapeutic ultrasound in the treatment of stenosing tenosynovitis of thumb flexor tendon.Methods A total of 138 patients with stenosing tenosynovitis of thumb flexor tendon admitted to the PLA General Hospital from January 2019 to December 2022 were enrolled in this study.They were divided into research group and control group,with 69 patients in each group.Patients in the control group were given injection of medication,and the patients in the research group were treated with extracorporeal shock wave combined with therapeutic ultrasound.Clinical effects,Quinnell grade and visual analogue scale(VAS)score before and 3 months after treatment were recorded.Results All the patients were followed up for 3 months.The total effective rate of the research group was 95.65%,which was significantly higher than that of the control group(69.56%,P<0.05).Quinnell grade was significantly decreased in both groups after treatment,especially in the research group(P<0.05).The pain was decreased in both groups after treatment,and the VAS score of the research group was significantly lower than that of the control group one week,one month,and three months after treatment(P<0.05).Conclusion The therapy of extracorporeal shock wave combined with ultrasound is safe,acceptable,effective and non-invasive in the treatment of stenosing tenosynovitis of thumb flexor tendon which is worthy of popularization and application.

The aim of this study was to evaluate the roles of interleukin (IL)-17A in risk stratification and prognosis of patients with sepsis-associated acute kidney injury (SAKI). Methods: We enrolled 146 sepsis patients (84 non-SAKI and 62 SAKI patients) admitted to the emergency department from November 2020 to November 2021. Patients with SAKI were differentiated based on the severity of acute kidney injury. All clinical parameters were evaluated upon admission before administering antibiotic treatment. Inflammatory cytokines were assessed using flow cytometry and the Pylon 3D automated immunoassay system (ET Healthcare). In addition, a receiver operating characteristic (ROC) curve was utilized to determine the prognostic values of IL-17A in SAKI. Results: The levels of creatinine, IL-2, IL-4, IL-6, IL-17A, tumor necrosis factor alpha, C-reactive protein, and procalcitonin (PCT) were significantly higher in the SAKI group than in the non-SAKI group (p < 0.05). The level of IL-17A revealed significant differences among stages 1, 2, and 3 in SAKI patients (p < 0.05). The mean levels of PCT, IL-4, and IL-17A were significantly higher in the non-survival group than in the survival group in SAKI patients (p < 0.05). In addition, the area under the ROC curve of IL-17A was 0.811. Moreover, the IL-17A cutoff for differentiating survivors from non-survivors was 4.7 pg/mL, of which the sensitivity and specificity were 77.4% and 71.0%, respectively. Conclusion: Elevated levels of IL-17A could predict that SAKI patients are significantly prone to worsening kidney injury with higher mortality. The usefulness of IL-17A in treating SAKI requires further research.

ObjectiveTo analyze the mental health status and its influencing factors in middle school students under the regular prevention and control of COVID-19， so as to provide references for the intervention and management of their mental health problems. MethodsFrom March 7 to 21， 2021， a stratified random sampling method was used to select 19 352 students from 17 schools in 3 districts and 9 counties of Linyi City， Shandong Province. Basic data were collected through a self-designed questionnaire. All students completed the Symptom Checklist 90 （SCL-90） to assess their mental health status. Then the factors affecting the mental health status of middle school students were screened using independent sample t-test， one-way ANOVA test and multiple stepwise regression analysis. Results① A total of 6 350 （32.81%） middle school students were found to have mental health problems. ② Each SCL-90 factor score and total average score yielded statistical difference among middle school students of different genders， relationships with classmate， closeness to friends， concerns about the epidemic， and pressure exerted by schoolwork （P<0.01）. Each SCL-90 factor score and total average score of middle school students were significant different in terms of the hours of smartphone usage for recreation per day， sleep duration per night in hours and exercise frequency （P<0.01）. ③ Multiple stepwise regression analysis denoted that female gender， poor relationship with classmate， no close friend and long hours of smartphone usage for recreation were the risk factors for mental health of middle school students （β=0.096， 0.183， 0.064， 0.232， P<0.01）. ConclusionThe prevalence rate of mild mental health problems is quite high among middle school students under the regular epidemic prevention and control. Additionally， female gender， poor relationship with classmate， no close friend and long hours of smartphone usage for recreation have a negative impact on middle school students' mental health.

Objective:To investigate the effects of intravenous thrombolysis combined with Xingnaojing injection on hemodynamic indexes and neurological function in patients with cerebral infarction. Methods:A total of 142 patients with cerebral infarction who were treated in Xing An Meng Hospital from April 2020 to May 2021 were included in this study. They were randomly divided into a control group ( n = 71, intravenous thrombolysis) and a Xingnaojing injection group ( n = 71, intravenous thrombolysis + Xingnaojing injection). Intracranial arterial hemodynamic indexes, National Institutes of Health Stroke Scale score, Fugl-Meyer Assessment Scale score, serum inflammatory factors, oxidative stress indexes, brain injury markers, and the incidence of adverse reactions were compared between the two groups. Results:After treatment, serum levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were significantly lower in the Xingnaojing injection group than the control group [interleukin-1β: (4.05 ± 0.83) ng/L vs. (6.85 ± 1.02) ng/L, interleukin-6: (43.61 ± 5.14) ng/L vs. (60.31 ± 7.04) ng/L, tumor necrosis factor-α: (35.93 ± 4.25) ng/L vs. (20.93 ± 3.11) ng/L, t = 17.94, 16.14, 15.37, all P < 0.001]. After treatment, the mean blood flow velocities of the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery in the Xingnaojing injection group were significantly higher than those in the control group [anterior cerebral artery: (49.36 ± 5.28) cm/s vs. (41.15 ± 5.12) cm/s, middle cerebral artery: (61.27 ± 7.02) cm/s vs. (50.19 ± 6.08) cm/s, posterior cerebral artery: (44.92 ± 5.63) cm/s vs. (37.26 ± 4.93) cm/s, t = 9.40, 10.05, 8.62, all P < 0.001]. After treatment, the National Institutes of Health Stroke Scale score and Fugl-Meyer Assessment Scale score in the Xingnaojing injection group were superior to those in the control group [National Institutes of Health Stroke Scale score: (10.36 ± 1.52) points vs. (14.62 ± 2.05) points, Fugl-Meyer Assessment Scale score: (76.19 ± 8.08) points vs. (65.28 ± 7.14) points, t = 14.06, 8.52, both P < 0.05]. After treatment, the serum level of malondialdehyde in the Xingnaojing injection group was significantly higher than that in the control group [(6.35 ± 1.02) μmol/L vs. (10.05 ± 1.63) μmol/L), t = 16.21, P < 0.001]. The serum level of superoxide dismutase in the Xingnaojing injection group was significantly lower than that in the control group [(114.31 ± 13.69) U/L vs. (92.25 ± 10.16) U/L), t = 10.90, P < 0.001]. Serum levels of neuron-specific enolase and S100β in the Xingnaojing injection group were significantly lower than those in the control group [neuron-specific enolase: (24.01 ± 3.24) IU/L vs. (30.31 ± 4.02) IU/L, S100β: (0.73 ± 0.17) ng/L vs. (1.13 ± 0.22) ng/L, t = 10.28, 12.12, both P < 0.001). There was a significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Intravenous thrombolysis combined with Xingnaojing injection for the treatment of cerebral infarction can improve intracranial hemodynamics, reduce the inflammatory response and oxidative stress, and alleviate brain tissue injury. The combined therapy is beneficial to protect the neurological function of patients with cerebral infarction and is highly safe.

ABSTRACT: Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. REGISTRATION Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.
Humans ; Meningioma/pathology* ; Consensus ; Neurosurgical Procedures ; Meningeal Neoplasms/pathology*