BACKGROUND:There is a very close relationship between osteoporosis and periodontal disease in postmenopausal women, but the mechanism remains unclear. OBJECTIVE:To investigate the expression of nuclear factor-κB in the alveolar bone andinterleukin-17 in the serum and gingiva in the mouse model of osteoporosis caused by ovariectomy. METHODS:Female mice aged 3 months were randomly divided into ovariectomy and sham operation groups. At 6 months after surgery, the mouse models were evaluated histologically on the submandibular bone and thigh bone stained with hematoxylin and eosin. In the submandibular bone, the expression levels of OCN and Runx2 were detected by RT-PCR, and the expression level of nuclear factor-κB was detected by immunohistochemical staining and western blot assay. Besides, the expression level of interleukin-17 in the serum and gingival homogenate was evaluated using Cytometric Beads Array. RESULTS AND CONCLUSION:The thigh bone in the ovariectomy group revealed the thin cortical bone, enlarged marrow cavity, and increased resorption lacunae, as well as fewer, thinner trabeculae with lower density and irregular structure. Compared with the sham operation group, the expression levels of OCN and Runx2 in the alveolar bone were decreased in the ovariectomy group. The activation of nuclear factor-κB (P65)appeared with P65 positive expression in the submandibular bone in the ovariectomy group, and the relative expression level was higher than that in the sham operation group. The serum level of interleukin-17 in the ovariectomy group was higher than that in the sham operation group, but the level in the gingival tissue showed no significant difference between the two groups. These results indicate that estrogen deficiency after ovariectomy can activate nuclear factor-κB signal pathway to play a role in periodontal osteolysis. However interleukin-17 in the local periodontal tissue may not be a key cytokine to damage the periodontal tissue.

Objective To investigate the relationship between nodular goiter and thyroid cancer and the causes of postoperative recurrence in patients with nodular goiter(NG) undergoing operative treatment. Methods The clinical date of 199 cases of NG were retrospectively analysed. Results Pathological examination revealed that 7 cases were accompanied by thyroid cancer including 2 micro-cancer, all the 7 cases were papillary carcinomas. The postoperative recurrent rate of NG was 11.5%(18 cases).Thyroid nodule reccurrence rate in patients received - operative thyroxin replacement therapy was significantly lower than that in patients not received thyroxin therapy( P

T cells engineered with chimeric antigen receptor (CAR) have been successfully applied to treat advanced refractory B cell malignancy.However,many challenges remain in extending its application toward the treatment of solid tumors.The immunosuppressive nature of tumor microenvironment is considered one of the key factors limiting CAR-T efficacy.One negative regulator of T cell activity is lymphocyte activation gene-3 (LAG-3).We successfully generated LAG-3 knockout T and CAR-T cells with high efficiency using CRISPR-Cas9 mediated gene editing and found that the viability and immune phenotype were not dramatically changed during in vitro culture.LAG-3 knockout CAR-T cells displayed robust antigen-specific antitumor activity in cell culture and in murine xenograft model,which is comparable to standard CAR-T cells.Our study demonstrates an efficient approach to silence immune checkpoint in CAR-T cells via gene editing.

Objective To explore the clinical characteristics of rotavirus associated mild encephalopathy/encephalitis with reversible splenial lesion(RAMERS).Methods RAMERS cases were collected from December 2017 to January 2018 at the Department of Neurology,Jiangxi Children's Hospital.The clinical and electroencephalogram characteristics of 14 patients with RAMERS were retrospectively investigated.Data was analyzed by using SPSS 19.0 software.Results Fourteen cases of RAMERS were tested,9 males,and 5 females,with the average age of (27.00 ±6.45) months,and all cases suffered from the generalized tonic-clonic seizures,57.14％ (8/14 cases) had cluster seizure (at lest 2 times/day),convulsions occurred (3.14 ± 1.29) days after gastroenteritis,and 64.29％ (9/14 cases) had pathologic fever (38 ℃ or higher).The background of electroencephalogram(EEG) was characterized by nonspecific rhythmic slow waves in 10 cases (71.43 ％,10/14 cases),normal in 3 cases (21.43 ％,3/14 cases),and interictal EEG performed in 1 case(7.14％,1/14 cases) which was characterized by focal discharges of spikes in the forehead,central,and all of the EEG manifestations go back to normal after 2 weeks.Twelve patients' brain MRI showed solitary splenium of corpus callosum lesion,and two showed splenium of corpus callosum and bilateral symmetry white matter lesion.Conclusions RAMERS is a special type of reversible splenial lesion syndrome,which occurs predominantly in infants and young children.It is characterized by gastroenteritis,benign infantile convulsion,cluster seizure and nonspecific rhythmic slow waves in the background of EEG.Prognosis is usually excellent.Head MRI reexamination is not recommended as a routine procedure to avoid overtreatment.

Objective:To explore relationship between serum 25-hydroxy vitamin D ( 25OHD ) level and ketosis-prone in patients with newly-diagnosed type 2 diabetes mellitus(T2DM).Methods:One hundred and thirty-four patients with newly diagnosed T2DM (103 males, 31 females) admitted in The Third Affiliated Hospital, Southern Medical University from January 2017 to January 2019 were enrolled into this study, including 36 patients with ketosis-prone (KPDM group) and 98 patients without ketosis(NKPDM group). Clinical characteristics, including height, weight, and history of hypertensive disease were collected. Serum 25OHD levels, lipid profile, islet function and glycosylated hemoglobin (HbA 1C)levels, ICA, IAA, GAD-Ab, etc., were measured. Results:Among the 134 patients, the patients with vitamin D deficiency, insufficiency, and sufficiency were 71 cases(52.99%), 52 cases(38.81%), and 11 cases(8.20%), respectively. KPDM group had significantly lower serum 25OHD level than NKPDM group[(44.12±9.77) nmol/L vs (55.35±15.31) nmol/L, P<0.01]. The rate of vitamin D deficiency was significantly higher in KPDM group compared to that in NKPDM group [(77.78% vs 43.88%), P<0.01]. The prevalence of KPDM varied significantly in different vitamin D status groups( P<0.01). Logistic regression analysis suggested that low serum 25OHD, younger age, high HbA 1C, and triglyceride were risk factors to ketosis-prone in newly diagnosed T2DM( P<0.01). Conclusion:Vitamin D deficiency is a common problem in newly diagnosed T2DM, especially in KPDM. Low serum 25OHD level seems to be an independent risk factor for ketosis-prone in patients with newly diagnosed T2DM.

Objective:To analyze the association between the pre-pregnancy oral microbiota of women and fetal overgrowth, and the possible mechanisms involved.Methods:A nested case-control study design based on a pre-pregnancy cohort was used to select 51 mothers who delivered macrosomia and/or large-for-gestational-age (LGA) infants from the population recruited at the Maternal and Child Health Care Hospital of Jiading District in Shanghai from October 2016 to December 2021 as the case group. A control group was formed by selecting 204 mothers who delivered infants with normal birth weight and appropriate for gestational age during the same period, in a 1:4 ratio. The LGA subgroup consisted of 48 mothers who delivered LGA infants from the total population, and a corresponding control group of 192 was randomly selected from the remaining mothers who delivered non-LGA infants in a 1∶4 ratio for the LGA subgroup analysis. The 16S rRNA gene sequencing technique was utilized to detect pre-pregnancy saliva samples to compare the characteristics of the oral microbiota, differential microorganisms, and differential functional pathways between groups. Nonparametric Wilcoxon rank-sum tests, two independent samples t-tests, or Chi-square (or Fisher's exact) tests were used for statistical analysis. Factor analysis was conducted on the pre-pregnancy diet data of women, and the primary dietary pattern of each study subject was identified based on the highest score of the dietary pattern factors. For microbiota count data, α and β diversity indices were calculated using R and QIIME2 software, and the corresponding microbiota functional count data were acquired through PICRUSt2. Results:(1) General data: There was no significant difference in the time interval from pre-pregnancy sampling to pregnancy and from sampling to delivery between the two groups. In the case group, there were three cases of macrosomia and 48 cases (94.1%) of LGA. The corresponding control group for the LGA subgroup consisted of 192 cases. There were no significant differences in dietary patterns between the case group and the control group. (2) α diversity analysis: The species richness index of the case group was lower than that of the control group [(367.27±84.57) vs. (408.71±93.08), multivariate analysis, P=0.009], while no significant differences were found between the two groups in the Shannon and Simpson indices; the species richness index of the LGA subgroup was also lower than that of the corresponding control group [(371.04±83.92) vs. (408.04±94.21), multivariate analysis, P=0.033], with no significant differences in the Shannon and Simpson indices. (3) β diversity analysis: There was a statistically significant difference in the unweighted UniFrac distance of the oral microbiota between the case group and the control group ( R2=0.006, F=1.479, P=0.048). No significant differences were found in the β diversity indices of the oral microbiota between the LGA subgroup and the corresponding control group. (4) Differential microbiota analysis: There were 14 differential microbiotas from phylum to genus between the case group and the control group. At the genus level, members of the G1 genus of the Streptococcaceae were enriched in the case group, while the Lautropia, Dialister, Leptotrichia, and Rothia were enriched in the control group. In the LGA subgroup and its corresponding control group, there were 14 differential microbiota from phylum to genus; at the genus level, Leptotrichia, Rothia, G6 genus of the Saccharibacteria, and Selenomonas were enriched in the control group (all LDA value>2, and all P<0.05). (5) Differential functional analysis: In the case group, metabolic pathways such as nicotinate degradation [log 2 fold change ( FC)=3.510, q=0.005], de novo synthesis of pyrimidine nucleotides (log 2FC=0.078, q=0.005), and L-tyrosine degradation pathway (log 2FC=0.710, q=0.034) were enriched in the oral microbiota of women. In the LGA subgroup, compared to the corresponding control group, metabolic pathways related to nicotinate degradation were enriched in the oral microbiota (log 2FC=3.660, q=0.012). Conclusions:There are differences in the structure of the pre-pregnancy oral microbiota of mothers with overgrown fetuses compared to those with normally grown fetuses, and mothers of normally grown fetuses show higher diversity in their pre-pregnancy oral microbiota. The enrichment of certain pathogenic bacteria and the reduction of symbiotic bacteria in the pre-pregnancy oral microbiota are associated with fetal overgrowth, and this association may be mediated by functional pathways such as nicotinate degradation.

As a member of the AFF (AF4/FMR2) family, AFF4 is a transcription elongation factor that is a component of the super elongation complex. AFF4 serves as a scaffolding protein that connects transcription factors and promotes gene transcription through elongation and chromatin remodelling. Here, we investigated the effect of AFF4 on human dental follicle cells (DFCs) in osteogenic differentiation. In this study, we found that small interfering RNA-mediated depletion of AFF4 resulted in decreased alkaline phosphatase (ALP) activity and impaired mineralization. In addition, the expression of osteogenic-related genes (DLX5, SP7, RUNX2 and BGLAP) was significantly downregulated. In contrast, lentivirus-mediated overexpression of AFF4 significantly enhanced the osteogenic potential of human DFCs. Mechanistically, we found that both the mRNA and protein levels of ALKBH1, a critical regulator of epigenetics, changed in accordance with AFF4 expression levels. Overexpression of ALKBH1 in AFF4-depleted DFCs partially rescued the impairment of osteogenic differentiation. Our data indicated that AFF4 promoted the osteogenic differentiation of DFCs by upregulating the transcription of ALKBH1.
Biomarkers ; metabolism ; Cell Differentiation ; Cells, Cultured ; Dental Sac ; drug effects ; metabolism ; Gene Expression Regulation ; Humans ; Osteogenesis ; genetics ; Repressor Proteins ; Transcription Factors ; genetics ; metabolism ; Transcriptional Elongation Factors ; metabolism