Objective Tto evaluate the effect of low intensity pulsed ultrasound(LIPUS)on the migration and phagocytosis ability of lipopolysaccharide(LPS)-induced RAW264.7 macrophages and on macrophage behavior under inflammation.Methods An in vitro activated RAW264.7 macrophage model was developed using LPS.Cell viability was assessed using a CCK-8 assay to explore the effect of LIPUS on activated and inactivated macrophages.Wound healing assays were employed to measure the effect of LIPUS on macrophage migration,and the Transwell assay was employed when LPS was used as a chemoattractant.Phagocytosis ability was examined using confocal microscopy and flow cytometry by observing the FITC fluorescence signal of internalized pHrodo Green E.coli BioParticles Conjugate.Results An activated RAW264.7 macrophage model was successfully developed using 100 ng/mL LPS.LIPUS inhibited the migration of inactivated macrophages into scratch areas as well as guided cell migration.However,cell viability and phagocytosis remained unchanged.Conclusion LIPUS may inhibit RAW264.7 migration but not affect the phagocytosis ability of the macrophages.

Background and objective Invasive mucinous adenocarcinoma(IMA)was a rare and specific type of lung adenocarcinoma,which was often characterized by fewer lymphatic metastases.Therefore,it was difficult to evaluate the prognosis of these tumors based on the existing tumor-node-metastasis(TNM)staging.So,this study aimed to develop Nomo-grams to predict outcomes of patients with pathologic N0 in resected IMA.Methods According to the inclusion criteria and exclusion criteria,IMA patients with pathologic N0 in The Affiliated Lihuili Hospital of Ningbo University(training cohort,n=78)and Ningbo No.2 Hospital(validation cohort,n=66)were reviewed between July 2012 and May 2017.The prognostic value of the clinicopathological features in the training cohort was analyzed and prognostic prediction models were established,and the performances of models were evaluated.Finally,the validation cohort data was put in for external validation.Results Univariate analysis showed that pneumonic type,larger tumor size,mixed mucinous/non-mucinous component,and higher overall stage were significant influence factors of 5-year progression-free survival(PFS)and overall survival(OS).Multivariate analysis further indicated that type of imaging,tumor size,mucinous component were the independent prognostic factors for poor 5-year PFS and OS.Moreover,the 5-year PFS and OS rates were 62.82％and 75.64％,respectively.In subgroups,the sur-vival analysis also showed that the pneumonic type and mixed mucinous/non-mucinous patients had significantly poorer 5-year PFS and OS compared with solitary type and pure mucinous patients,respectively.The C-index of Nomograms with 5-year PFS and OS were 0.815(95％CI:0.741-0.889)and 0.767(95％CI:0.669-0.865).The calibration curve and decision curve analysis(DCA)of both models showed good predictive performances in both cohorts.Conclusion The Nomograms based on clinicopathological characteristics in a certain extent,can be used as an effective prognostic tool for patients with pathologic N0 after IMA resection.

Objective: To understand and analyze the epidemiological characteristics of dental caries in children and its effects on jaw function, so as to prevent occurrence of abnormality of jaw function. Methods: In October 2020, 860 cases of children from 5 kindergartens and 3 primary schools in Beijing were selected by adopting the convenience sampling method. All of them received oral examination, and the questionnaire according to the fourth national oral health epidemiological survey standard, including demographic information, eating habits, oral hygiene habits, oral health care,etc. The epidemiological characteristics of dental caries in children and its effects on jaw function were analyzed. Results: A total of 190 children had dental caries, with a dental caries incidence rate of 22.09%. Dental caries in children s deciduous teeth or permanent teeth was related to age, residence, parents education level,whethe to eat before going to bed, whether eating sweet food, tooth brushing age, daily brushing frequency, whether parents have assisted tooth brushing, whether regular oral examination, whether parents have received oral health guidance( χ 2= 5.04 ,4.70，75.37，7.91，12.03，9.30，7.64，255.47，253.27，11.38, P <0.05). Compared with the noncaries group[(81.52±3.16， 80.54± 1.52，1.92±0.25，31.52±1.62，33.63±3.41，50.72±1.68)°], the sella nasion A point(SNA), sella nasion B point(SNB),A point nasion B point(ANB),frankfot horizontal mandibular plane angle(FH MP),skull nasion mandibular plane angle(SN MP),anteriors relationship palataplane mandibular(Ptm ANS) decreased in the dental caries group[(78.62±2.11，79.35±1.02，1.68±0.32，30.69±0.45，32.15±3.02，48.62±1.21)°](t=78.62,79.35,10.94, 30.69, 32.15, 48.62, P<0.05). Conclusion The prevalence of caries in children was high and jaw structure abnormalities and dysfunction. It is suggested that caries prevention and control work should be carried out early to strengthen the prevention and control of oral disease education work.

Long noncoding RNAs (lncRNAs) play a critical role in the regulation of atherosclerosis. Here, we investigated the role of the lncRNA growth arrest-specific 5 (lncR-GAS5) in atherogenesis. We found that the enforced expression of lncR-GAS5 contributed to the development of atherosclerosis, which presented as increased plaque size and reduced collagen content. Moreover, impaired autophagy was observed, as shown by a decreased LC3II/LC3I protein ratio and an elevated P62 level in lncR-GAS5-overexpressing human aortic endothelial cells. By contrast, lncR-GAS5 knockdown promoted autophagy. Moreover, serine/arginine-rich splicing factor 10 (SRSF10) knockdown increased the LC3II/LC3I ratio and decreased the P62 level, thus enhancing the formation of autophagic vacuoles, autolysosomes, and autophagosomes. Mechanistically, lncR-GAS5 regulated the downstream splicing factor SRSF10 to impair autophagy in the endothelium, which was reversed by the knockdown of SRSF10. Further results revealed that overexpression of the lncR-GAS5-targeted gene miR-193-5p promoted autophagy and autophagic vacuole accumulation by repressing its direct target gene, SRSF10. Notably, miR-193-5p overexpression decreased plaque size and increased collagen content. Altogether, these findings demonstrate that lncR-GAS5 partially contributes to atherogenesis and plaque instability by impairing endothelial autophagy. In conclusion, lncR-GAS5 overexpression arrested endothelial autophagy through the miR-193-5p/SRSF10 signaling pathway. Thus, miR-193-5p/SRSF10 may serve as a novel treatment target for atherosclerosis.
Humans ; Atherosclerosis/genetics* ; Autophagy/genetics* ; Cell Cycle Proteins/metabolism* ; Endothelial Cells/metabolism* ; Endothelium/metabolism* ; MicroRNAs/metabolism* ; Repressor Proteins/metabolism* ; RNA Splicing Factors ; Serine-Arginine Splicing Factors/genetics* ; RNA, Long Noncoding/metabolism*

Objective:To evaluate the effect of intraoperative individualized systolic blood pressure (SBP) management on myocardial injury after hip replacement in elderly patients at high risks of hypertension.Methods:One hundred and eighty-two patients of either sex, aged 60-89 yr, with body mass index of 18-26 kg/m 2, with a history of hypertension requiring drug treatment and stratified high risk factors of cardiovascular risk factors, scheduled for elective hip replacement under general anesthesia, were divided into 2 groups ( n=91 each) using a random number table method: routine management group and individualized SBP management group. Individualized SBP management group maintained the intraoperative SBP at 90%-110% of the baseline value, and routine management group implemented blood pressure management according to the current routine clinical pathway.The intermedian cubital venous blood samples were collected before surgery and at 24, 48, and 72 h after surgery for determination of the serum concentrations of high sensitivity cardiac troponin T. Postoperative myocardial injury and myocardial infarction were also recorded. The 30-day all-cause mortality was recorded on day 30 after surgery. Results:The incidence of postoperative myocardial injury and serum concentrations of high sensitivity cardiac troponin T at 24, 48 and 72 h after surgery were significantly decreased, and the length of hospital stay was shortened in individualized SBP management group as compared with routine management group ( P<0.05). Conclusions:Intraoperative individualized SBP management can reduce the postoperative myocardial injury in elderly patients at high risk of hypertension undergoing hip replacement.

  Objective  Different from other etiologies of early-onset scoliosis (EOS), congenital early-onset scoliosis (CEOS) is mainly linked to vertebral anomalies, such as formation failures and segmentation failures at the apex segments. So far, there is little research on CEOS patients who have completed traditional growing rods (TGR) treatment, and the initial outcomes of TGR with or without apical control technique (ACT) are different. Therefore, we compared the "final" results of CEOS patients who completed TGR treatment with or without ACT.  Methods  We conducted a retrospective study of CEOS patients who completed TGR treatment from 2007—2020. They either had final fusion or were followed up after reaching skeletal maturity. We split the patients into two groups based on whether they had ACT with TGR or not. The ACT-TGR group had apical vertebrectomy/hemivertebrectomy with short fusion and TGR. The TGR-only group had only TGR. We looked at their demographic features, radiographic measurements, and complications.  Results  This study enrolled 46 CEOS patients, of which 13 patients were in the ACT-TGR group and 33 patients in the TGR group. The ACT-TGR group had a longer distraction interval (1.17 years vs. 0.75 years). The ACT-TGR group had a larger preoperative main curve [87.00(63.50, 98.00)], but the residual curve degrees were comparable between the two groups at the last follow-up (P=0.354). At the last follow-up, the T1-12 and T1-S1 heights were similar between the two groups. The ACT-TGR group had a lower number of implant-related complications per patient (0.77 vs. 1.48). Three patients in the ACT-TGR group underwent final fusion, while 17 patients in the TGR group underwent final fusion (P=0.060).  Conclusions  Both ACT-TGR and traditional TGR coud effectively correct deformity and preserve spinal growth in CEOS patients. ACT-TGR had a better corrective effect on patients with severe deformity and did not have a significant impact on spinal height. For patients with acceptable correction, spontaneous fusion and without implant failure, retaining the implant and continuing observation could be a strategy for graduating from growing rod treatment.

Background: Chronic exposure to elevated levels of saturated fatty acids results in pancreatic β-cell senescence. However, targets and effective agents for preventing stearic acid-induced β-cell senescence are still lacking. Although melatonin administration can protect β-cells against lipotoxicity through anti-senescence processes, the precise underlying mechanisms still need to be explored. Therefore, we investigated the anti-senescence effect of melatonin on stearic acid-treated mouse β-cells and elucidated the possible role of microRNAs in this process. Methods: β-Cell senescence was identified by measuring the expression of senescence-related genes and senescence-associated β-galactosidase staining. Gain- and loss-of-function approaches were used to investigate the involvement of microRNAs in stearic acid-evoked β-cell senescence and dysfunction. Bioinformatics analyses and luciferase reporter activity assays were applied to predict the direct targets of microRNAs. Results: Long-term exposure to a high concentration of stearic acid-induced senescence and upregulated miR-146a-5p and miR- 8114 expression in both mouse islets and β-TC6 cell lines. Melatonin effectively suppressed this process and reduced the levels of these two miRNAs. A remarkable reversibility of stearic acid-induced β-cell senescence and dysfunction was observed after silencing miR-146a-5p and miR-8114. Moreover, V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa) was verified as a direct target of miR-146a-5p and miR-8114. Melatonin also significantly ameliorated senescence and dysfunction in miR-146a-5pand miR-8114-transfected β-cells. Conclusion These data demonstrate that melatonin protects against stearic acid-induced β-cell senescence by inhibiting miR-146a- 5p and miR-8114 and upregulating Mafa expression. This not only provides novel targets for preventing stearic acid-induced β-cell dysfunction, but also points to melatonin as a promising drug to combat type 2 diabetes progression.

The dorsal lingual epithelium, which is composed of taste buds and keratinocytes differentiated from K14⁺ basal cells, discriminates taste compounds and maintains the epithelial barrier. N6-methyladenosine (m⁶A) is the most abundant mRNA modification in eukaryotic cells. How METTL3-mediated m⁶A modification regulates K14⁺ basal cell fate during dorsal lingual epithelium formation and regeneration remains unclear. Here we show knockout of Mettl3 in K14⁺ cells reduced the taste buds and enhanced keratinocytes. Deletion of Mettl3 led to increased basal cell proliferation and decreased cell division in taste buds. Conditional Mettl3 knock-in mice showed little impact on taste buds or keratinization, but displayed increased proliferation of cells around taste buds in a protective manner during post-irradiation recovery. Mechanically, we revealed that the most frequent m⁶A modifications were enriched in Hippo and Wnt signaling, and specific peaks were observed near the stop codons of Lats1 and FZD7. Our study elucidates that METTL3 is essential for taste bud formation and could promote the quantity recovery of taste bud after radiation.
Animals ; Epithelium/metabolism* ; Homeostasis ; Methylation ; Methyltransferases/metabolism* ; Mice ; RNA ; Taste Buds/metabolism*

Lin28 is a highly conserved RNA-binding protein, including Lin28a and Lin28b. Lin28 is involved in many physiological processes such as cell differentiation, growth and metabolism. In recent years, it has been found that Lin28 is closely related to the pathogenesis and development of numerous major diseases. The relationships between Lin28 and related diseases such as tumor, cardiovascular disease and diabetes are reviewed in this article.

The oral cavity of each person is home to hundreds of bacterial species.While taxa for oral diseases have been studied using culture-based characterization as well as amplicon sequencing,metagenomic and genomic information remains scarce compared to the fecal microbiome.Here,using metagenomic shotgun data for 3346 oral metagenomic samples together with 808 published samples,we obtain 56,213 metagenome-assembled genomes(MAGs),and more than 64％of the 3589 species-level genome bins(SGBs)contain no publicly available genomes.The resulting genome collection is representative of samples around the world and contains many genomes from candi-date phyla radiation(CPR)that lack monoculture.Also,it enables the discovery of new taxa such as a genus Candidatus Bgiplasma within the family Acholeplasmataceae.Large-scale metagenomic data from massive samples also allow the assembly of strains from important oral taxa such as Por-phyromonas and Neisseria.The oral microbes encode genes that could potentially metabolize drugs.Apart from these findings,a strongly male-enriched Campylobacter species was identified.Oral sam-ples would be more user-friendly collected than fecal samples and have the potential for disease diagnosis.Thus,these data lay down a genomic framework for future inquiries of the human oral microbiome.