RNA interference-based osteoanabolic therapy for osteoporosis by a bone-formation surface targeting delivery system.

RNA interference (RNAi)-based gene therapy that promotes anabolic bone formation is an effective approach for addressing osteoporosis. However, the selection of target gene and tissue-specific delivery systems has hindered the progression of this strategy. In this study, we identified casein kinase-2 interacting protein-1 encoding gene (Ckip-1), a negative regulator of bone formation, as an effective target of small interfering RNAs (siRNAs) for improving bone mass. Moreover, an impressive (DSS)6-Liposome (Lipos) nanoparticle system that could target the bone formation surface was synthesized to enhance the delivery of Ckip-1 siRNA to osteogenic lineage cells. The in vitro results confirmed that the (DSS)6-Lipos system could efficaciously improve the intracellular delivery of Ckip-1 siRNA without obvious cell toxicity. The in vivo application of the delivery system showed specific accumulation of siRNA in osteogenic cells located around the bone formation surface. Bone-related analysis indicated increased bone mass and improved bone microarchitecture in mice with ovariectomy-induced osteoporosis. Moreover, the biomechanical characteristics of the tibia were enhanced significantly, indicating increased resistance to fragile fracture induced by osteoporosis. Thus, (DSS)6-Lipos-Ckip-1 siRNA-based osteoanabolic therapy may be a promising option for the treatment of osteoporosis.

Use of a digitally guided triple technique for bone reduction, implant placement, and immediate interim prostheses in complete-arch implant surgery.

A digitally guided triple technique for bone reduction, implant placement, and immediate interim prostheses in complete-arch implant surgery is presented. This technique integrates bone reduction and implant placement information into a dual-function surgical template and introduces a digital approach to fabricating immediate interim implant-supported fixed dental prostheses with the same occlusal relationship as the one evaluated with diagnostic removable prostheses.

Actinomyces qiguomingii sp. nov., isolated from the Pantholops hodgsonii.

Two previously undescribed, Gram-stain-positive, rod-shaped strains, 410T and 553, were isolated from faeces of the Tibetan antelope (Pantholops hodgsonii) from the Tibet-Qinghai Plateau, PR China. The optimum growth conditions of the two novel strains were 1 % (w/v) NaCl, 37 °C and pH 7. The end products from glucose fermentation included ethanol and lactic acid. Based on results of 16S rRNA gene sequence comparison and phylogenetic and phylogenomic analyses, strains 410T and 553 were classified into the genus Actinomyces, and were closely related to Actinomyces ruminicola (97.6 %), Actinomyces oricola (93.5 %) and Actinomyces dentalis (90.8 %). The genomic G+C content of strain 410T was 67.4 mol%. Digital DNA-DNA hybridization values between strain 410T and each of the closely related species were under 70 %. The respiratory quinones were MK-10 (68 %) and MK-9 (32 %). The main cellular fatty acids of the isolates were C16 : 0, followed by C18 : 1 ω9c. The major polar lipids were diphosphatidylglycerol and phosphatidylinositol-mannoside. The whole-cell sugars contained rhamnose, ribose and glucose. The diagnostic amino acids of cell-wall peptidoglycan included alanine, glutamic acid, lysine and ornithine. The results of biochemical, chemotaxonomic and genotypic analyses revealed that the two novel strains represent a novel species of genus Actinomyces, for which the name Actinomyces qiguomingii sp. nov. is proposed. The type strain is 410T (=CGMCC 1.16361T= DSM 106201T).

Actinomyces marmotae sp. nov. and Actinomyces procaprae sp. nov. isolated from wild animals and reclassification of Actinomyces liubingyangii and Actinomyces tangfeifanii as Boudabousia liubingyangii comb. nov. and Boudabousia tangfeifanii comb. nov., respectively.

Four Gram-stain-positive, catalase-negative, non-spore-forming, rod-shaped bacterial strains (zg-325T, zg329, dk561T and dk752) were isolated from the respiratory tract of marmot (Marmota himalayana) and the faeces of Tibetan gazelle (Procapra picticaudata) from the Qinghai-Tibet Plateau of PR China. The results of 16S rRNA gene sequence-based phylogenetic analyses indicated that strains zg-325T and dk561T represent members of the genus Actinomyces, most similar to Actinomyces denticolens DSM 20671T and Actinomyces ruminicola B71T, respectively. The DNA G+C contents of strains zg-325T and dk561T were 71.6 and 69.3 mol%, respectively. The digital DNA-DNA hybridization values of strains zg-325T and dk561T with their most closely related species were below the 70 % threshold for species demarcation. The four strains grew best at 35 °C in air containing 5 % CO2 on brain heart infusion (BHI) agar with 5 % sheep blood. All four strains had C18:1ω9c and C16:0 as the major cellular fatty acids. MK-8 and MK-9 were the major menaquinones in zg-325T while MK-10 was predominant in dk561T. The major polar lipids included diphosphatidylglycerol and phosphatidylinositol. On the basis of several lines of evidence from phenotypic and phylogenetic analyses, zg-325T and dk561T represent novel species of the genus Actinomyces, for which the name Actinomyces marmotae sp. nov. and Actinomyces procaprae sp. nov. are proposed. The type strains are zg-325T (=GDMCC 1.1724T=JCM 34091T) and dk561T (=CGMCC 4.7566T=JCM 33484T). We also propose, on the basis of the phylogenetic results herein, the reclassification of Actinomyces liubingyangii and Actinomyces tangfeifanii as Boudabousia liubingyangii comb. nov. and Boudabousia tangfeifanii comb. nov., respectively.

Actinomyces gaoshouyii sp. nov., isolated from plateau pika (Ochotona curzoniae).

Two strains (pika_113T and pika_114) of a previously undescribed Actinomyces-like bacterium were recovered from the intestinal contents of plateau pika (Ochotona curzoniae) on the Tibet-Qinghai Plateau, China. Results from biochemical characterization indicated that the two strains were phenotypically homogeneous and distinct from other previously described species of the genus Actinomyces. Based on the comparison of 16S rRNA gene sequences and genome analysis, the bacteria were determined to be a hitherto unknown subline within the genus Actinomyces, being most closely related to type strains of Actinomyces denticolens and Actinomyces timonensis with a respective 97.2 and 97.1 % similarity in their 16S rRNA gene sequences. Phylogenetic analyses confirmed that pika_113T was well separated from any other recognized species of the genus Actinomyces and within the cluster with A. denticolens and A. timonensis. The genome of strain pika_113T displayed less than 42 % relatedness in DNA-DNA hybridization with all the available genomes of existing species of the genus Actinomyces in the NCBI database. Collectively, based on the phenotypic characteristics and phylogenetic analyses results, we propose the novel isolates as representatives of Actinomyces gaoshouyii sp. nov. The type strain of Actinomyces gaoshouyii is pika_113T (=CGMCC 4.7372T=DSM 104049T), with a genomic DNA G+C content of 71 mol%.

A smart ratiometric fluoresence and colorimetry dual-responsive sensor for morin determination based on the complex between carbon quantum dots and polyethyleneimine.

As a representative flavonoid, morin exhibits multi-biological activities, but its abuse endangers human health. Developing advanced technology for morin determination is urgently needed. In this study, a dual-responsive approach was reported for morin based on the complexing of carbon quantum dots (CQDs) and polyethyleneimine (PEI). The CQDs were fabricated via an improved hydrothermal method employing tyrosine and malic acid. Binding with PEI induced an 8-fold emission enhancement and a slight red-shift to 445 nm of CQDs because of the complexing of PEI and CQDs. Further morin introduction led to the blue emission (445 nm) quenching of CQDs-PEI and a yellow emission (560 nm) generation, which contributed a ratiometric fluorescence approach for morin determination between 2.0 and 32 µM, with a limit of detection (LOD) of 45 nM. Meanwhile, under sunlight the color of CQDs-PEI became yellow upon morin addition, which developed a colorimetric method for morin determination in a wide range between 2.0 and 100 µM (LOD = 69 nM). The developed dual-responsive method either displayed accurate results for morin in diluted human and bovine serum, being potential for actual sample analysis. Finally, a visual detection based on the smartphone was constructed and applied for the real-time determination of morin.

Biomimetic Mineralized Fiber Bundle-Inspired Scaffolding Surface on Polyetheretherketone Implants Promotes Osseointegration.

The stress shielding effect caused by traditional metal implants is circumvented by using polyetheretherketone (PEEK), due to its excellent mechanical properties; however, the biologically inert nature of PEEK limits its application. Endowing PEEK with biological activity to promote osseointegration would increase its applicability for bone replacement implants. A biomimetic study is performed, inspired by mineralized collagen fiber bundles that contact bone marrow mesenchymal stem cells (BMMSCs) on the native trabecular bone surface. The PEEK surface (P) is first sulfonated with sulfuric acid to form a porous network structure (sP). The surface is then encapsulated with amorphous hydroxyapatite (HA) by magnetron sputtering to form a biomimetic scaffold that resembles mineralized collagen fiber bundles (sPHA). Amorphous HA simulates the composition of osteogenic regions in vivo and exhibits strong biological activity. In vitro results show that more favorable cell adhesion and osteogenic differentiation can be attained with the novelsurface of sPHA than with SP. The results of in vivo experiments show that sPHA exhibits osteoinductive and osteoconductive activity and facilitates bone formation and osseointegration. Therefore, the surface modification strategy can significantly improve the biological activity of PEEK, facilitate effective osseointegration, and inspire further bionic modification of other inert polymers similar to PEEK.

[Oral dexketoprofen tromethamine for preemptive analgesia in extraction of impacted teeth: a randomized controlled double-blind trial].

PURPOSE: To study the preemptive analgesic effect of dexketoprofen tromethamine in extraction of impacted teeth. METHODS: Twenty patients with bilateral mandibular impacted teeth were selected, and were randomly divided into dexketoprofen tromethamine group(experimental group) and placebo group(control group). The pain scores of patients at 0.5, 2, 4, 8, 12, and 24 hours after tooth extraction were counted by numeric rating scale(NRS), and the total dosage of emergent analgesic drugs used in 24 hours was recorded. COX analysis method was used to compare the interval time and the number of cases of first application of emergent analgesic drugs after two operations, and the survival curve was drawn. SPSS 20.0 software package was used for data analysis. RESULTS: The NRS scores of postoperative pain in the experimental group were significantly lower than those in the control group at 2, 4, 8 and 12 hours after operation (P＜0.05). The dose of emergent analgesics used in the experimental group for 24 h was significantly lower than that in the control group (P＜0.05). Survival curve showed that the interval time between the first application of analgesics in the experimental group was significantly longer than that in the control group(P＜0.05). CONCLUSIONS: Dexketoprofen tromethamine can achieve obvious analgesic effect within 12 hours, but the analgesic effect is not obvious after 12 hours.

[Study on the thickness and morphology of lingual bone of impacted mandibular third molar based on CBCT and Simplant 3D reconstruction].

PURPOSE: The potential relationship between impacted mandibular third molar and lingual bone thickness was investigated by quantitative measurement of lingual bone thickness, and a three-dimensional visualization model of lingual bone was established. METHODS: Image data of 200 cases of mandibular impacted third molar were collected from the database of Hefei Stomatological Hospital. Thickness measurement and three-dimensional reconstruction of lingual bone at different measurement sites were performed by Simplant Pro software. Statistical analysis was performed using SPSS 22.0 software package, and the comparison of lingual thickness at different measurement sites was performed using rank sum test. Whether the thickness of bone plate was "high-risk type" was taken as the result variable, different related factors were analyzed by logistic regression. RESULTS: The lingual bone at the middle point of the root of the third molar was the thinnest. Multiple teeth, mesio-inclined and dial-inclined teeth, and Class Ⅱ and Ⅲ impacted teeth had thin lingual bone(P＜0.05). The mesial and distal inclines were observed, and the lingual bone was thin in the root apical region of the teeth in Class Ⅱ and Class Ⅲ(P＜0.05). In the lower impacted teeth, the thin lingual bone at the central crown site was more likely to be found in Class Ⅲ teeth(P＜0.05). CONCLUSIONS: The thickness of lingual bone was related to the number of impacted tooth roots, tilt direction and impacted type. In the extraction of impacted teeth, the above factors should be considered, and the injury of lingual nerve, lingual bone and surrounding soft tissue should be vigilant.

[Evaluation of the effect of digital crown extension guide in aesthetic restoration of anterior teeth].

PURPOSE: To evaluate the clinical effect of three-dimensional digital smile design (3D-DSD) combined with double positioning crown extension guide in aesthetic restoration of anterior teeth. METHODS: Twenty patients who needed aesthetic crown lengthening and full crown restoration of upper anterior teeth were selected and randomly divided into the experimental group and control group, with 10 cases in each group. The experimental group carried out 3D-DSD, after confirming the plan, 3D printed double positioning crown extension guides were used to guide aesthetic crown lengthening, and full crown was completed 3 months after operation. The control group used traditional aesthetic crown lengthening and full crown restoration. PES/WES evaluation was performed before operation, three months and six months after operation. Visual analogue scales(VAS) were used to evaluate patient satisfaction 6 and 7 months after surgery, and the repeatability evaluation of VAS was conducted. The correlation between PES/WES score and overall satisfaction was analyzed 6 months after operation. SPSS 23.0 software package was used for statistical analysis. RESULTS: The PES/WES scores of the two groups of patients at 3 months and 6 months after operation were higher than those before operation(P＜0.05). The two groups showed that the scores of the experimental group were significantly higher than those of the control group for PES 3 months after operation, PES and WES 6 months after operation(P＜0.05).Satisfaction survey results showed that the intra-group correlation coefficient of the two VAS results was 0.956(P＜0.05),and crown length-to-width ratio, smile curve, personality characteristics, patient participation and overall satisfaction in the experimental group were better than those of the control group(P＜0.05).The results of Speraman correlation analysis showed that PES and WES scores at 6 months after operation were positively correlated with overall satisfaction (rs1=0.905, P＜0.001; rs2=0.460, P=0.041). CONCLUSIONS: 3D digital smile design combined with double positioning crown extension guide guides the anterior aesthetic crown lengthening and restoration treatment, which can improve the effect of pink and white aesthetics after treatment and patient satisfaction.

[The relationships between different surgical approaches for maxillary sinus augmentation and implant failure and complications: a retrospective cohort study].

PURPOSE: To investigate the 5-year survival and complication rates of implants placed in grafted sinuses with different surgical approaches and analyze the causes for failure. METHODS: This study retrospectively observed the prognosis of patients who underwent maxillary sinus augmentation by means of lateral window technique(LWT) or transalveolar osteotomy technique (TOT) and simultaneously installed implants performed, in Hefei Stomatological Hospital. The primary predictor variables were surgical approaches, including LWT and TOT. The primary outcome measurement was the 5-year implant survival rate, complication rates and failure causes. Potential confounders included diabetes, age at surgery, gender, smoking habit, oral hygiene, tooth position, length and diameter of implants and type of prosthesis. Chi-square test and logistic regression analysis were performed with SPSS 21.0 software package. RESULTS: Fifty-nine patients (31 males and 28 females), installed with 93 implants, with a mean age of (61.3±10.1) years old, were enrolled. Over (5±1.2) years of follow-up, five implants failed, with a total survival rate of 94.6%. In detail, there were 3 failed implants in the LWT group and 2 failed implants in the TOT group, for a survival rate of 85.7% and 97.2%, respectively. Chi-square test showed that smoking habit (P=0.010), oral hygiene(P=0.037) as well as operative approach(P=0.040) were significantly associated with the final survival rates, multivariate logistic regression analysis displayed that smoking habit (OR=0.030, 95%CI: 0.002-0.493, P=0.014) was still associated with the finial survival rates. Surgical approach(P=0.025) was markedly related to causes for the failed implants. Of which, three (100%) failed implants in the LWT group was due to poor osseointegration and implant mobility 3 months after sinus augmentation, and 2(100%) in the TOT group was because of persistent peri-implantitis and loss of the graft or alveolar bone 4 years after sinus augmentation. Smoking habit was also significantly relevant to complication rates(P=0.014), and the occurrence incidence of controllable peri-implantitis in patient having a smoking habit was relatively higher, accounting for 6.8%(6/88), compared with patients without smoking habit. Significant relationship between surgical approaches and implant complications was not observed(P=0.051). CONCLUSIONS: Different surgical approaches for maxillary sinus augmentation do not significantly correlate with implant survival rates and implant complications. However, surgical approach is markedly related to the causes of failed implants. Smoking will lead to a decreased implant survival rate and controllable peri-implantitis.

[Different concentration of lidocaine used for an exodontia of the impacted mandibular third molar].

PURPOSE: To investigate the anesthesia outcomes of 1% lidocaine with 1∶100 000 epinephrine (EPI) for inferior alveolar nerve, lingual nerve and buccal nerve block, compared with 2% lidocaine with 1∶100 000 EPI. METHODS: A study with a cross-over design, with each patient also serving as their own control, was implemented to estimate the clinical outcomes. Predictor variable was 1% lidocaine with 1∶100 000 EPI versus 2% lidocaine with 1∶100 000 EPI. Outcome variables were patients' responses to pain on injection, onset time of anesthetizing, efficacy of anesthesia, and the time to sensation return for the lower lip and tongue. Patients reported pain level at every experimental stage with a 10-point Numerical Rating Scale(NRS). Three weeks later, the patients were tested with the alternate drug combinations. The same outcomes were assessed. A verification of treatment difference was performed using SPSS 17.0 software package. RESULTS: Twenty-one patients were recruited and completed the study protocol. Sixty-two percent of the patients were women and 38% were men with a median age of 24 years [interquartile range (IQR), 20-30 yr]. Patients reported significantly lower pain scores with 1% lidocaine (1.09,95%CI，0.77-1.41) on injection, compared with 2% lidocaine (1.66, 95%CI, 1.33-1.99) (P=0.010). Patients undergoing 1% lidocaine with 1∶100 000 EPI (52-63 s) had a markedly quicker onset time of anesthetizing than those using 2% lidocaine with 1∶100 000 EPI (259-335 s, P=0.000). The efficacy of anesthesia between 2 groups was not significantly different (P=0.751). Among the patients with the pain values of 1~3, there were 9 patients(100%) perceiving slight pain when splitting teeth was performed in 1% lidocaine group, while 4 patients(57%) felt slight pain when elevating soft flaps was performed and 3 patients(43%) perceived mild pain when splitting teeth was performed in 2% lidocaine group (P=0.019). The time to sensation return for the lower lip and tongue was significantly different between the 2 drug formulations (P=0.000), with an extended period of average 61 min (52-69 min) in 2% lidocaine group. CONCLUSIONS: 1% lidocaine with EPI plays a similar role in clinical outcomes for inferior alveolar nerve, lingual nerve and buccal nerve block as 2% lidocaine with EPI, which produces lower pain on injection as well as a relatively short time to sensation return. The reasons for slight pain during surgical operation are a relative lower efficacy of anesthesia on the inferior alveolar nerve in 1% lidocaine group, and on the buccal nerve anesthesia in 2% lidocaine group.

[Clinical analysis of impacted supernumerary teeth in 115 patients].

PURPOSE: To retrospectively analyze the clinical characteristics of impacted supernumerary teeth in 115 patients. METHODS: One hundred and fifteen patients with im-pacted supernumerary teeth who were admitted to the Department of Oral and Max-illofacial Surgery of Hefei Stomatological Hospital were selected randomly. The age, sex, number of teeth, location, direction, clinical manifestation, anaes-thesia method and operation time were analyzed retrospectively, T test and Chi-square test were used to determine the statistical differences with SPSS 19.0 software package. RESULTS: Among 115 patients, there were 176 impacted supernu-merary, most of them were in mixed dentition period (66.96%), the sex ratio was 2.29:1, and Most patients (59.1%) had one supernumerary tooth, followed by two supernumerary teeth(33.9%). Most supernumerary teeth were located in the middle of the maxilla (68.2%). Inverted ones were the most common (52.8%). The most common symptoms were delayed eruption, displacement, crowding, torsion and space of the adjacent teeth. 92.2% of patients underwent general anesthesia. The dee-per the locations of impacted supernumerary were, the longer the operation time was. CONCLUSIONS: There are regional characteristics of supernumerary teeth in Hefei City, which can provide a reference for clinical diagnosis and treatment.

Can Platforms Affect the Safety and Efficacy of Drug-Eluting Stents in the Era of Biodegradable Polymers?: A Meta-Analysis of 34,850 Randomized Individuals.

OBJECTIVE: In the era of bare metal stents (BMSs), alloys have been considered to be better materials for stent design than stainless steel. In the era of biodegradable polymer drug-eluting stents (BP-DESs), the safety and efficacy of BP-DESs with different metal platforms (stainless steel or alloys) have not yet been reported, although their polymers are eventually absorbed, and only the metal platforms remain in the body. This study sought to determine the clinical safety and efficacy of BP-DESs with different platforms compared with other stents (other DESs and BMSs). METHODS: PubMed, Embase and Clinical Trials.gov were searched for randomized controlled trials (RCTs) that compared BP-DESs with other stents. After performing pooled analysis of BP-DESs and other stents, we performed a subgroup analysis using two classification methods: stent platform and follow-up time. The study characteristics, patient characteristics and clinical outcomes were abstracted. RESULTS: Forty RCTs (49 studies) comprising 34,850 patients were included. Biodegradable polymer stainless drug-eluting stents (BP-stainless DESs) were superior to the other stents [mainly stainless drug-eluting stents (DESs)] in terms of pooled definite/probable stent thrombosis (ST) (OR [95% CI] = 0.76[0.61-0.95], p = 0.02), long-term definite/probable ST (OR [95% CI] = 0.73[0.57-0.94], p = 0.01), very late definite/probable ST (OR [95% CI] = 0.56[0.33-0.93], p = 0.03) and long-term definite ST. BP-stainless DESs had lower rates of pooled, mid-term and long-term target vessel revascularization (TVR) and target lesion revascularization (TLR) than the other stainless DESs and BMSs. Furthermore, BP-stainless DESs were associated with lower rates of long-term death than other stainless DESs and lower rates of mid-term myocardial infarction than BMSs. However, only the mid-term and long-term TVR rates were superior in BP-alloy DESs compared with the other stents. CONCLUSION: Our results indirectly suggest that BP-stainless DESs may offer more benefits than BP-alloy DESs in the era of BP-DESs. Further well-designed RCTs comparing BP-stainless with BP-alloy DESs are needed to confirm which platform is better.

[Application of nitrous oxide / oxygen inhalation sedation in tooth extraction of elderly patients with hypertension].

PURPOSE: To investigate the safety and efficacy of nitrous oxide/oxygen inhalation sedation assisted in elderly hypertensive patients under local anesthesia during tooth extraction. METHODS: Forty elderly patients (age≥70 years) with hypertension who needed tooth extraction with electrocardiographic monitoring were selected, and divided into experimental and control groups randomly, with 20 patients in each group. The experimental group was treated with nitrous oxide/oxygen inhalation sedation and local anesthesia for surgery, the control group underwent tooth extraction under local anesthesia. Heart rate, blood pressure, as well as differences of operative time in all groups before surgery, during operation and after surgery were observed and compared. SPSS 11.0 software package was used for statistical analysis. RESULTS: The intraoperative HR, BP of patients in the control group was significantly higher than those of patients in the experimental group (P<0.05). HR, BP were relatively stable during the whole procedure in the experimental group. Compared with the control group, surgery was significantly longer in the experimental group (P<0.05). The difference was statistically significant. CONCLUSIONS: Nitrous oxide/oxygen inhalation sedation assisted local anesthesia can be a safe and effective anesthetic method in tooth extraction of elderly patients with hypertension. Supported by Medical Science and Technology Progress Project of Nanjing City(YKK11040).

[Supernumerary teeth: report of a rare case and review of the literature].

Supernumerary teeth is a well-recognized clinical phenomenon. Multiple supernumerary teeth are commonly associated with variable syndromes. However the multiple supernumerary teeth reported in mandibular and maxilla premolar region of an 14-year-old female patient without any associated systemic condition/syndrome is a rare case. A review of the literature relating to supernumerary teeth is presented including possible presentations, diagnostic features and treatment options.