BACKGROUND: Periodontitis is characterized by alveolar bone resorption, aggravated by osteoblast dysfunction, and associated with intracellular oxidative stress linked to the nuclear factor erythroid 2-related factor 2 (NRF2) level. We evaluated the molecular mechanism of periodontitis onset and development and the role of NRF2 in osteogenic differentiation. METHODS: Primary murine mandibular osteoblasts were extracted and exposed to Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) or other stimuli. Reactive oxygen species (ROS) and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining were used to detect intracellular oxidative stress. Alkaline phosphatase staining and alizarin red S staining were used to detect the osteogenic differentiation of osteoblasts. Immunofluorescence and western blotting were used to determine the changes in the mitogen-activated protein kinase (MAPK) pathway and related molecule activities. Immunofluorescence colocalization and co-immunoprecipitation were performed to examine the nuclear translocation of NRF2 and its interaction with dual-specific phosphatase 1 (DUSP1) in cells. RESULTS: Ligated tissue samples showed higher alveolar bone resorption rate and lower NRF2 level than healthy periodontal tissue samples. Pg-LPS increased intracellular oxidative stress levels and inhibited osteogenic differentiation, whereas changes in NRF2 expression were correlated with changes in the oxidative stress and osteogenesis rate. NRF2 promoted the dephosphorylation of the MAPK pathway by nuclear translocation and the upregulation of DUSP1 expression, thus enhancing the osteogenic differentiation capacity of mandibular osteoblasts. The interaction between NRF2 and DUSP1 was observed. CONCLUSIONS: NRF2 and its nuclear translocation can regulate the osteogenic differentiation of mandibular osteoblasts under Pg-LPS conditions by interacting with DUSP1 in a process linked to the MAPK pathway. These findings form the basis of periodontitis treatment.
Animals ; NF-E2-Related Factor 2/physiology* ; Lipopolysaccharides/pharmacology* ; Osteoblasts/drug effects* ; Mice ; Porphyromonas gingivalis/chemistry* ; Cell Differentiation ; Osteogenesis ; Dual Specificity Phosphatase 1/metabolism* ; Mandible/cytology* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Periodontitis/metabolism* ; Cells, Cultured ; Male ; Cell Nucleus/metabolism*

Objective:To explore the expression levels and the clinical significance of serum secreted frizzled-related protein 5 (SFRP5) and miR-124-3p in patients with hypertension during pregnancy.Methods:Ninety-eight patients with hypertension during pregnancy diagnosed from Jan. 2019 to Feb. 2022 were selected as the observation group. According to the degree of the condition of patients, they were divided into 41 cases of pregnancy hypertension, 32 cases of mild preeclampsia, and 25 cases of severe preeclampsia, and 80 healthy subjects during the same period were selected as the control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression level of serum SFRP5 in patients, real-time fluorescence quantitative method (qRT-PCR) was used to detect the expression level of miR-124-3p. The relationship between SFRP5, miR-124-3p levels and clinicopathological indicators in patients with hypertension in pregnancy was analyzed, Pearson correlation analysis was used to analyze the correlation between SFRP5 and miR-124-3p. Multivariate Logistic regression was used to analyze the risk factors of hypertension in pregnancy.Results:Compared with the control group, the serum SFRP5 expression level of the observation group [ (33.78±5.21) ng/L vs (43.34±8.56) ng/L] was down-regulated, while the miR-124-3p level [ (2.16±0.41) vs (1.01±0.17) ] was up-regulated, and the serum SFRP5 level of the observation group decreased with the severity of the disease[ (38.43±6.37) ng/L (33.18±5.14) ng/L (26.94±3.38) ng/L], while the level of miR-124-3p increased with the severity of the disease[ (1.62±0.24) (2.19±0.43) (3.01±0.69) ], the difference was statistically significant ( P<0.05) . The expression levels of SFRP5 and miR-124-3p in the serum of patients with hypertension in pregnancy were related to the age, pregnancy, pre-pregnancy BMI, and fasting blood glucose level of patients ( P<0.05) , but not related to the gestational age of patients ( P>0.05) . Bioinformatics TargetScan website showed that SFRP5 and miR-124-3p had binding sites. Pearson correlation analysis showed that SFRP5 and miR-124-3p were negatively correlated ( r=-0.610, P<0.05) . Multivariate Logistic regression analysis showed that SFRP5 was a protective factor for pregnancy-induced hypertension in pregnant women, and miR-124-3p was a risk factor ( P<0.05) . Conclusion:The serum levels of SFRP5 and miR-124-3p are abnormally expressed in patients with hypertension during pregnancy, and there is a certain relationship with the degree of disease. Both are involved in the occurrence and development of hypertension during pregnancy.

COVID-19 and its causative pathogen SARS-CoV-2 have rushed the world into a stag-gering pandemic in a few months, and a global fight against both has been intensifying. Here, we describe an analysis procedure where genome composition and its variables are related, through the genetic code to molecular mechanisms, based on understanding of RNA replication and its feed-back loop from mutation to viral proteome sequence fraternity including effective sites on the replicase-transcriptase complex. Our analysis starts with primary sequence information, identity-based phylogeny based on 22,051 SARS-CoV-2 sequences, and evaluation of sequence variation patterns as mutation spectra and its 12 permutations among organized clades. All are tailored to two key mechanisms: strand-biased and function-associated mutations. Our findings are listed as follows: 1) The most dominant mutation is C-to-U permutation, whose abundant second-codon-position counts alter amino acid composition toward higher molecular weight and lower hydropho-bicity, albeit assumed most slightly deleterious. 2) The second abundance group includes three negative-strand mutations (U-to-C, A-to-G, and G-to-A) and a positive-strand mutation (G-to-U) due to DNA repair mechanisms after cellular abasic events. 3) A clade-associated biased muta-tion trend is found attributable to elevated level of negative-sense strand synthesis. 4) Within-clade permutation variation is very informative for associating non-synonymous mutations and viral pro-teome changes. These findings demand a platform where emerging mutations are mapped onto mostly subtle but fast-adjusting viral proteomes and transcriptomes, to provide biological and clinical information after logical convergence for effective pharmaceutical and diagnostic applica-tions. Such actions are in desperate need, especially in the middle of the War against COVID-19.

Objective To explore the occurrence of fetal chromosomal abnormalities among pregnant women with an adverse reproductive history using traditional karyotyping and single nucleotide polymorphism microarray(SNP-array)technology.Methods Totally 94 in 2 163(4.35%)cases of singleton pregnant women with an adverse reproductive history were performed amniocentesis in Jinhua Maternal and Child Health Care Hospital from June 2015 to June 2017. Traditional karyotyping and SNP-array were employed simultaneously for prenatal diagnosis,and the detection rates of the two methods were compared. Results All of the 94 specimens were successfully analyzed, 11 cases were found with chromosomal anomaly, the overall detection rate was 11.7%(11/94). Seven (7.4%,7/94) abnormalities cases were detected by karyotyping,and 7(7.4%)by SNP-array.The karyotyping results of trisomy 21,and 45,X and the deletion of chromosome 13 were consistent with SNP-array.Only 3(3.2%,3/94)microdeletion/duplications (the sizes of duplications and deletions were between 422.4-1 708.4 kb)and 1(1/4)loss of heterozygosity were detected by SNP-array,but were missed by karyotyping.Furthermore, 2 cases′copy number variation were found pathogenic gene related, while the other 2 were considered benign or variant of uncertain significance. Four cases(4/7)of abnormalities were detected by karyotyping, while confirmed balanced translocation and inversion by SNP-array.All patients were informed and chosen to continue the pregnancy.Conclusions The rate of abnormal fetal chromosomes in pregnant women with an adverse reproductive history is still high.SNP-array is a new molecular genetic technique,and combined with use of traditional karyotyping,it could improve the detection rate of fetal chromosomal abnormalities and reduce abortion rate, thus providing a basis for genetic counseling and prenatal diagnosis.

Objective To systematically evaluate and analyze the evidence level of randomized controlled trials (RCT) of preoperative skin preparation for emergency percutaneous coronary intervention (PCI), and to understand the current research status and evidence level of preoperative skin preparation randomized controlled trials for emergency PCI, and provide reference for skin preparation for emergency PCI. Methods PubMed, EMbase, The Cochrane Library, CINAHL, JBI, CBM, CNKI, Wanfang DATA were searched by computer from inception to March, 2018 for emergency PCI preoperative skin preparation randomized controlled trials. Two evidence panel members searched and selected articles independently and the quality was assessed in accordance with Cochrane Manual. The articles were analyzed with Review Manager 5.3, and the evidence quality was assessed with GRADE profiler 3.6.1 software. Results A total of 5 RCTs were included, of which the number of RCTs with grade A quality was 1 and the number of RCTs with grade B was 4. The results of the Meta analysis showed that there was no significant difference in the incidence of skin infections at the postoperative puncture site by conventional methods for routine removal of surgical wild hair and no removal of hair prior to emergency PCI (P＜0.05). In addition, regular removal of hair before surgery may result in prolonged preoperative preparation and may cause psychological discomfort to the patient. After the GRADE system rating, the quality of the evidence body was of a lower level. Conclusions It is more beneficial to shorten the treatment time without routine removal of all the hair at the puncture site and the surrounding patients. The evidence included is not yet certain whether the incomplete removal of hair can reduce the infection rate. In the future, more large-scale, multi-center, high-quality research should be carried out to provide more credible evidence for this study.

Objective To improve the traditional treatment of retrograde pulpitis, using Periocline adjuvant therapy, to evaluate its clinical effect.Methods From January 2015 to 2017 in January, our hospital 70 patients treated with retrograde pulpitis.The patients were randomly divided into two groups.The observation group of 35 cases, adopt the traditional treatment methods (periodontal treatment and dental pulp treatment), 35 cases in the control group based on conventional therapy, the adjuvant treatment of periocline.The related indexes and treatment effects were observed.Results After treatment, the indexes of the two groups of patients were significantly decreased compared with the control group[(1.57±0.50),(3.37±1.88),(4.89±1.60),(5.31±1.39)],the observation group decreased much more[(0.79±0.24),(2.01±1.14),(4.01±1.38),(4.11±0.62)], the difference was significant (P<0.05).At the same time, the effective rate of the observation group was 94.29% (33 cases), and the effective rate of the control group was 74.29% (26 cases), the difference was significant (P<0.05).Conclusion Based on conventional therapy, using Periocline adjuvant therapy, can improve the therapeutic effect of retrograde pulpitis, has significant value of application and promotion.

Objective To investigate the effects of minocycline hydrochloride ointment on collagenase in gingival crevicular fluid.Methods 60 patients with chronic periodontitis treated in our hospital from January 2015 to December 2016 were selected as the research object, the patients were divided into two groups according to their intervention methods, 30 cases in each group.The control group was treated with ultrasound clean governance and iodine glycerol, the observation group was treated with ultrasound clean governance and minocycline hydrochloride ointment The experimental data of the two groups were compared.Results The index change of gingival crevicular fluid volume plaque index,,depth of exploration and clinical attachment loss in the observation group were better than those in the control group, the difference between the two groups was statistically significant (P<0.05);The clinical therapeutic effect of the observation group(93.3%)was better than that of the control group(73.3%), and the difference between the two groups was statistically significant (P<0.05).The incidence of adverse reactions in the observed group(10.0%)was lower than that in the control group(26.7%), and the difference between the two groups was statistically significant (P<0.05).Conclusion Minocycline hydrochloride ointment can affect the level of collagenase in gingival crevicular fluid, and the clinical effect of the treatment of chronic periodontal disease is significant.

Objective To study the effect of minocycline hydrochloride ointment and ibuprofen on serum concentration of chronic periodontitis . Methods 86 patients with chronic periodontitis treated in our hospital from June 2014 to June 2016 were selected and randomly divided into two groups:observation group 43 cases, using minocycline hydrochloride ointment combined with ibuprofen treatment , the control group 43 cases, only the use of minocycline hydrochloride ointment for treatment.After treatment, the clinical efficacy of the two groups were observed, the level of plaque, the level of attachment, the level of gingival sulcus bleeding and the probing depth of periodontal pocket were recorded, the levels of IL-10, TNF-α, hs-CRP and IL-8 in serum and the incidence of adverse reactions were measured.Results The total effective rate was 90.7% in the observation group and 74.4%in the control group, which was significantly higher than that in the control group, the difference was statistically significant (P<0.05).The probing depth of the periodontal pocket, gingival sulcus bleeding index, attachment level and plaque index decreased to varying degrees in the two groups before and after treatment, the difference was statistically significant (P<0.05), patients in the observation group were significantly lower than those in the control group, the difference was statistically significant (P<0.05).After treatment, the levels of IL-8, hs-CRP and TNF-αin serum of the two groups decreased, IL-10 levels increased in different degrees, the difference was statistically significant (P<0.05).The observation group was better than the control group, the difference was statistically significant ( P<0.05 ) .Conclusion Minocycline hydrochloride ointment combined with ibuprofen has a good effect on patients with chronic periodontitis.It can effectively relieve the patient's condition and improve the serum concentration of patients.

Objective To explore and analyze the clinical efficacy and adverse reactions of total glucosides of paeony (TGP) and vitamin B2 in the treatment of recurrent aphthous ulcers (RAU) . Methods 120 patients of RAU were randomly divided into TGP group and vitamin B2 group, 60 cases in each group. The TGP group received TGP capsules after meals, three times a day, 0.6g/d. Vitamin B2 group received vitamin B2 tablets, three times a day, 5mg/d, 8 weeks for one course. The ulcer change, visual analogue scale (VAS) and efficacy were observed. Results After treatment, the VAS scores were significantly reduced in two groups(P<0.05), and the above indicators of TGP group were better than vitamin B2 group(P<0.05). The total efficacy in TGP group was higher than that in vitamin B2 group (P<0.05). There was minor adverse reactions in TGP group and no significant adverse reactions in vitamin B2 group.Conclusion TGP has good efficacy and safety in the treatment of recurrent aphthous ulcers. The TGP has significant effect than that of vitamin B2.

Objective To observe the effects of adiponectin on mRNA and protein expressions of connective tissue growth factor (CTGF) in hepatic stellate cells (HSCs) and the levels of procollagen type Ⅲ (PC Ⅲ) and hyaluronic acid (HA).Methods Cultured rat HSCs were treated with different concentrations of adiponectin.CTGF mRNA and protein expressions were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Western Blot.The levels of PCⅢ and HA were detected by enzymelinked immunosorbent assay (ELISA).Results Compared with the control group,the result of RT-PCR showed that the four groups had different degrees of inhibitory effect,of which group D exhibited the strongest inhibitory effect.The absorbance ratio was 1.54 ±0.18,1.21 ±0.14,0.96 ±0.10,and 0.79 ± 0.08,respectively (t =2.42,P ＜0.05;t =2.73,P ＜0.05;t =3.28,P ＜0.01;t =4.67,P ＜0.01).Western Blot also indicated that four groups had different degrees of inhibitory effect,of which D group exhibited the strongest inhibitory effect.The ratio of integral absorption was 1.54 ± 0.18,1.21 ±0.14,0.96±0.10,and 0.79 ±0.08,respectively (t =2.84,P ＜0.01;t =4.05,P ＜0.01;t =6.25,P ＜0.01;t =9.72,P ＜0.01).The levels of PCⅢ and HA secreted in culture media were also decreased.It was significantly decreased with the concentration of adiponectin increased.Conclusion Adiponectin can inhibit the levels of PC Ⅲ and HA,which may be achieved through reducing CTGF mRNA and protein expressions.