BACKGROUND:Inflammation affects the osteogenic differentiation of periodontal ligament stem cells,and the osteogenic ability and autophagy level of periodontal ligament stem cells are closely related.However,there are no relevant reports on whether inflammation affects the osteogenic ability and autophagy level of periodontal ligament stem cells at different stages of osteogenic differentiation. OBJECTIVE:To explore alkaline phosphatase expression and autophagy periodontal ligament stem cells levels in periodontitis and normal conditions. METHODS:Periodontal ligament stem cells from normal and periodontitis patients were isolated and cultured,and underwent Vimentin,pan-CK,and Stro-1 fluorescence staining.At 3,7,and 14 days of osteogenic differentiation,western blot assay was used to detect the protein expression levels of alkaline phosphatase,LC3B,Beclin1,and ATG5 in normal and inflammatory periodontal ligament stem cells.The mRNA expression levels of alkaline phosphatase,bone sialoprotein,osteocalcin,Runx2,LC3B,Beclin1,and ATG5 were detected by real-time PCR. RESULTS AND CONCLUSION:(1)Stro-1 was positive,Vimentin was positive,and pan CK was negative in periodontal ligament stem cells.(2)At 3,7,and 14 days after osteogenic differentiation,compared with normal periodontal ligament stem cells,the mineralization nodules formed by periodontal ligament stem cells from inflammatory sources were significantly reduced(P<0.01);the expression of alkaline phosphatase protein and mRNA was significantly lower(P<0.05);the mRNA expression levels of bone sialoprotein,osteocalcin,and Runx2 were significantly decreased(P<0.05).(3)At 7 and 14 days after osteogenic differentiation,compared with normal periodontal ligament stem cells,the expression levels of ATG5,LC3B,and Beclin1 proteins and mRNA of periodontal ligament stem cells were downregulated(P<0.05).These findings suggest that inflammation reduces the activity of periodontal ligament stem cells in mineralizing nodule formation and the expression of alkaline phosphatase and weakens the autophagy potential of periodontal ligament stem cells at 7 and 14 days after osteogenic differentiation.

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

ObjectiveTo systematically evaluate the safety of interferon β-1a for treatment of corona virus disease 2019 （COVID-19）， and to provide references for interferon β-1a's clinical application. MethodsThis study was conducted with the database from US Food and Drug Administration adverse event reporting system （FAERS） from January 1， 2015 to March 31， 2021. Information component （IC） and reporting odds ratio （ROR） methods were applied for signal mining. ResultsA total of 463 700 records of COVID-19 were selected for analysis， and 45 positive drug adverse event signals were detected. Headache （IC₀₂₅=1.09， ROR₀₂₅=2.28）， pyrexia （IC₀₂₅=0.51， ROR₀₂₅=1.51） and multiple sclerosis relapse （IC₀₂₅=3.67， ROR₀₂₅=14.71） were positive adverse events with higher frequency. Autoimmune disorder （IC₀₂₅=4.42， ROR₀₂₅=24.03）， streptococcal infection （IC₀₂₅=4.12， ROR₀₂₅=19.82）， and multiple sclerosis relapse （IC₀₂₅=3.67， ROR₀₂₅=14.71） were positive adverse events. Acute lung injury， cardio-respiratory arrest and metabolic acidosis were associated with a higher proportion and frequency of death. ConclusionThere are certain safety issues with interferon β-1a in the treatment of COVID-19， and some adverse events with high frequency and high death rate deserve further attention by medical staffs.

Objective:To evaluate the feasibility of indocyanine green fluorescence imaging technology applied in thyroid surgery to identify parathyroid gland.Methods:From Oct 2021 to May 2022, data of 42 patients undergoing thyroidectomy via gasless unilateral axillary approach in Zhejiang Provincial Hospital of Traditional Chinese Medicine were retrospectively analyzed. Cases using intraoperative fluorescence imaging technology(42 cases) were compared with conventional laparocopic approach.Results:The number of parathyroid glands dissected in the study group 1.57±0.61 was higher than that in the control group 0.56± 0.59 ( t=-5.472, P<0.05). The PTH value of the study group was (2.88±1.23)pmol/L on the first day after operation, which was higher than that of the control group (2.16±0.10)pmol/L ( t=-1.844, P<0.05). The blood parathyroid hormone value on the third day(3.22±1.31)pmol/L was higher than that of the control group (2.55±0.81) pmol/L ( t=-2.041, P<0.05). There were 2 cases of hypoparathyroidism in the study group, less than 5 cases in the control group, but there was no significant difference between the two groups( χ2=0.942, P>0.05). There was 1 case of hypocalcemia in the study group and 3 cases in the control group ( χ2=0.731, P>0.05). Conclusion:Using indocyanine green fluorescence imaging technology to identify parathyroid gland is feasible, simple, fast, safe and effective.

Objective To investigate the effect of imatinib on the growth of A549 non-small cell lung cancer transplanted tumors and the expression of PDGFB and PDGFRβ proteins in tumor tissues and stroma in nude mice and to explore the underlying tumor suppression mechanism. Methods A transplantation tumor model of A549 non-small cell lung cancer was established in nude mice. The mice were then randomly divided into four groups: control group (0.9%NaCl), low-dose imatinib group (50 mg/(kg·d)), medium-dose imatinib group (100 mg/(kg·d)), and high-dose imatinib group (200 mg/(kg·d)). The effect of different concentrations of imatinib administered by continuous gavage on tumor growth was observed for 28 days. HE staining was performed to observe the pathological changes of tumor tissues. The expression of PDGF/PDGFR pathway-related proteins and the phosphorylation levels of AKT and ERK1/2 proteins in tumor tissues were detected by Western blot analysis. Double immunofluorescence staining was used to detect the expression of PDGFB and PDGFRβ proteins in the tumor stroma. Results Imatinib inhibited the growth of A549 non-small cell lung cancer cells in nude mice, suppressed the expression of PDGFB in tumor tissues, and decreased the phosphorylation levels of PDGFRβ, AKT, and ERK1/2. The expression of PDGFB and PDGFRβ in tumor stromal fibroblasts of the administered group was significantly lower than that of the control group. Conclusion Imatinib exhibits a pronounced inhibitory effect on A549 xenografts of nude mice with non-small cell lung cancer, and its antitumor mechanism may involve the downregulation of PDGFB and PDGFRβ expression in tumor stromal fibroblasts.

Objective: To understand the parenting styles of junior high school students in Beijing, to explore the relationship between parenting styles with students academic performance and the role of mental health in this association. Methods: From October 2019 to January 2020, a stratified random cluster sampling method was used to select 5 196 students in the first and second grades of 11 public junior high schools in urban and rural areas in Beijing, and Slort Egna Minnenar Barndoms Uppfostran-China,Middle School Students Mental Health Scale-60 and self designed questions were used in the questionnaire survey. Results: The average score of parenting style rejection dimension was (9.44±3.88), and the average score of emotional warmth dimension was (19.85±5.66). The average score of comprehensive score of students mental health was ( 1.92 ±0.73). Mental health score of girls was higher than boys (1.97±0.74)(1.87±0.71), and the differences were of statistical significance( t=5.06, P <0.01). Parental rejection and emotionally warm parenting styles were significantly correlated with students academic performance （ β =-0.54，1.15， P <0.01). Mental health played a negative moderating role between parenting style and students academic performance. The better students mental health were, the greater the influence of parenting style on academic performance. Conclusion Parenting style is related to children s academic performance. Parents should give their children more affirmation, encouragement and praise, in order to improve their academic performance.

Objective:To investigate the clinical efficacy of induced membrane technique in the staged treatment of adult chronic hematogenous osteomyelitis (CHOM) of long bone.Methods:The clinical data were retrospectively analyzed of the 22 adult patients with CHOM of long bone who had been admitted to the 920th Hospital, Joint Logistics Support Force of PLA from January 2016 to December 2019. There were 18 males and 4 females, aged from 16 to 56 years (average, 31.81 years). Their disease duration ranged from 0.6 to 42.0 years, averaging 18.4 years. By the Cierny-Mader anatomical classification, 4 cases were type Ⅰ, 6 cases Type Ⅲ, and 12 cases type Ⅳ. In the first stage, the bone defects were filled with antibiotic bone cement after thorough debridement. In the second stage when the infection had been controlled, the bone defects were repaired with bone grafts after removal of the bone cement. Bone healing time and complications were followed up. The treatment effects were evaluated by comparisons of the infection control indexes [including clinical manifestations like local redness, swelling, pus, and pain, and blood white blood cell count, C-Reactive protein (CRP), and erythrocyte sedimentation rate (ESR) as well] before the primary surgery, before the secondary surgery and at the last follow-up.Results:The volumes of the bone defects after stage-one debridement ranged from 54 cm 3 to 176 cm 3 (mean, 90.9 cm 3). All patients were followed up for 20 to 51 months (mean, 30.1 months) after surgery. All bone defects healed after 4 to 11 months (mean, 6.6 months). Postoperatively, infection developed at the bone extraction site of the posterior superior iliac spine in 3 cases and pain was observed at the donor site in one case, but the conditions were relieved after symptomatic treatment. Fracture and plate breakage occurred at the bone defect site in one case who had fallen down 7 months after operation, but responded to reoperation. The last follow-up revealed such symptoms as redness, swelling and pus discharge in none of the patients. The white blood cell count [(5.70 ± 1.57) × 10 9/L and (5.65 ± 1.58) × 10 9/L], CRP [(7.56 ± 2.57) mg/L and (7.25 ± 3.83) mg/L] and ESR [(9.64 ± 2.90) mm/h and (10.55 ± 5.23) mm/h] before the secondary surgery and at the last follow-up were significantly lower than those before the primary surgery [(8.24 ± 2.18) × 10 9/L, (49.54 ± 19.56) mg/L, and (42.68 ± 13.77) mm/h] (all P < 0.05). However, there were no significant differences between the indexes before the secondary surgery and at the last follow-up ( P > 0.05). Conclusion:In the staged treatment of adult CHOM of long bone, the induced membrane technique can effectively control infection, achieve repair of bone defects, and reduce complications.

Objective:To analyze the clinical teachers′ cognitive evaluation of the residency training system and faculty competency through a survey , which in the standardized residency training bases of Zhejiang province, in the hope of providing a basis for exploring and reforming the training and the mechanism.Methods:A web-based questionnaire survey was made from December 2017 to December 2019 on clinical teachers at training bases in Zhejiang province. Data cleaning and statistical analysis were made under Anaconda1 9.7, multiple groups of numerical variables were analyzed by one-way ANOVA, and classified variables were subject to χ2 analysis, while the analysis was carried out after binarization in the statistical calculation of multi-choice items. Results:3 141 of valid questionnaires were received. The clinical teachers at large highly recognize the competency degree expected of the teachers, while those items of relatively lower recognition were " the ability to regularly publish research papers" " the ability to guide the trainees′ living style" , and " the ability to use multimedia teaching materials" (41.13%, 46.23%, and 47.02% respectively). 77.36% of the teachers reported that they need coordination and management ability training, while 83.38% need teaching ability training. The proportion of teachers in need of teaching ability training was influenced by both professional title( χ2=18.703, P < 0.001)and seniority( χ2=14.471, P=0.006). For the subjective criteria by the teachers on faculty competency assessment criteria, the scoring ranks from high to low were clinical ability, medical ethics, and teaching awareness(8.91±1.35, 8.86±1.52 and 8.64±1.47 respectively). For the operability criteria, the scoring ranks from high to low were professional title, education, and faculty training(8.47±1.80, 8.36±1.86 and 8.19±1.91 respectively), while the outcomes were influenced by the administrative title, professional title and seniority( P < 0.05). Only 39.03% and 33.37% of clinical teachers were satisfied or somewhat satisfied with the existing incentives for residency training. Conclusions:The teachers′ recognition of the criteria for faculty competency evaluating and the need for teacher training were influenced by their characteristics, and they were unsatisfied with the existing incentive policies. These suggest comprehensive factors in formulating the evaluation standards, and measures for progressive faculty training and for improved incentive policies.

Based on observing the cytological characteristics of the flower buds of the functional male sterile line (S13) and the fertile line (F142) in eggplant, it was found that the disintegration period of the annular cell clusters in S13 anther was 2 days later than that of F142, and the cells of stomiun tissue and tapetum in F142 disintegrated on the blooming day, while it did not happen in S13. The comparative transcriptomic analysis showed that there were 1 436 differential expression genes (DEGs) (651 up-regulated and 785 down-regulated) in anthers of F142 and S13 at 8, 5 days before flowering and flowering day. The significance analysis of GO enrichment indicated that there were more unigene clusters involved in single cell biological process, metabolism process and cell process, and more catalytic activity and binding function were involved in molecular functions. Through KEGG annotation we found that the common DEGs were mainly enriched in the biosynthesis of secondary metabolites, metabolic pathway, protein processing in endoplasmic reticulum, biosynthesis of amino acids, carbon metabolism and plant hormone signal transduction. The fifteen genes co-expression modules were identified from 16 465 selected genes by weighted gene co-expression network analysis (WGCNA), three of which (Plum2, Royalblue and Bisque4 modules) were highly related to S13 during flower development. KEGG enrichment showed that the specific modules could be enriched in phenylpropanoid biosynthesis, photosynthesis, porphyrin and chlorophyll metabolism, α-linolenic acid metabolism, polysaccharide biosynthesis and metabolism, fatty acid degradation and the mutual transformation of pentose and glucuronic acid. These genes might play important roles during flower development of S13. It provided a reference for further study on the mechanism of anther dehiscence in eggplant.
Flowers/genetics* ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Humans ; Infertility, Male ; Male ; Metabolic Networks and Pathways/genetics* ; Solanum melongena/genetics* ; Transcriptome/genetics*