BACKGROUND:The light curing and fluoride light curing enamel adhesives have a certain sealing effect on the etched enamel surface.The fluoride light curing enamel adhesives can also achieve the anti-caries function by releasing fluoride ions.However,the existing researches lack the long-term tracing of fluoride release effect,especially the amount of local pathogenic bacteria after 1-3 months of local fluoride application. OBJECTIVE:To analyze the changes in the expression of Porphyromonas gingivalis and Streptococcus mutans in subgingival plaque of the upper anterior teeth adhered by different components of enamel adhesives in adolescent patients with fixed appliance. METHODS:Ninety adolescent patients who received orthodontic treatment in Shanghai Stomatological Hospital from January to December 2016 were enrolled,including 43 males and 47 females,with a mean age of(13.27±1.12)years.These patients were randomly divided into three groups(n=30 per group).In the chemical curing group,Unite? bonding resin was used to bond fixed appliances.In the light curing group,Transbond XT light curing resin was used to bond the fixed appliance.In the fluoride light curing group,GC light curing orthodontic adhesive was used to bond the fixed appliance with cement.The subgingival plaque was collected on the day of bonding,1st,2nd,and 3rd month follow-up reviews.The expressions of Porphyromonas gingivalis and Streptococcus mutans in subgingival plaque were detected by PCR. RESULTS AND CONCLUSION:(1)Intragroup comparison:With the increase of bonding time,Porphyromonas gingivalis expression increased significantly in the 3rd month in the chemical curing group(P<0.05).In the light curing group,Porphyromonas gingivalis showed a significant decrease in the 1st month(P<0.05).Porphyromonas gingivalis expression decreased significantly in the 1st and 2nd months compared with initial data in the fluoride light curing group(P<0.05).The expression of Streptococcus mutans was higher in the chemical curing group in the 1st,2nd,and 3rd months compared with the initial data(P<0.05).In the fluoride light curing group,the expression of Streptococcus mutans was lower in the 1st,2nd,and 3rd months compared with the initial data(P<0.05).There was no significant difference in the proliferation and expression of Streptococcus mutans during follow-up in the light curing group compared to the initial adhesion(P>0.05).(2)Intergroup comparison:In the 1st month,the expression of Porphyromonas gingivalis was lower in the light curing group and fluoride light curing group than that in the chemical curing group(P<0.05).In the 2nd and 3rd months,the expression of Porphyromonas gingivalis was lower in the fluoride light curing group than that in the light curing group and chemical curing group(P<0.05).In the 1st,2nd,and 3rd months,the expression of Streptococcus mutans was lower in the light curing group and fluoride light curing group than that in the chemical curing group(P<0.05).The expression of Streptococcus mutans was lower in the fluoride light curing group than that in the light curing group(P<0.05).(3)The results show that in the fixed orthodontic process,the use of different components of enamel adhesives has different effects on the proliferation and expression of oral Porphyromonas gingivalis and Streptococcus mutans in the short term.Fluoride light curing enamel adhesives at the initial stage can reduce the occurrence of enamel demineralization,caries,and periodontal inflammation.

Depressive disorder ranks as a major bur-den of disease worldwide,yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects.The lateral septum(LS)is thought to control of depression,however,the cellular and circuit substrates are largely unknown.Here,we identified a subpopulation of LS GABAergic adenosine A2A receptors(A2AR)-positive neurons mediating depres-sive symptoms via direct projects to the lateral habenula(LHb)and the dorsomedial hypothalamus(DMH).Activa-tion of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipula-tion of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive pheno-types.Thus,the optogenetic modulation(stimulation or inhibition)of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH,phenocopied depressive behaviors.Moreover,A2AR are upregulated in the LS in two male mouse mod-els of repeated stress-induced depression.This identifica-tion that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant poten-tial of A2AR antagonists,prompting their clinical transla-tion.

Humans ; Transcranial Magnetic Stimulation ; Pain Management ; Psychotic Disorders/therapy* ; Depressive Disorder, Major ; Treatment Outcome ; Transcranial Direct Current Stimulation

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint (TMJ) osteoarthritis (OA); however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4 (Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2 and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore, Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.
Aggrecans/metabolism* ; Animals ; Cartilage, Articular/metabolism* ; Chondrocytes/pathology* ; Cytoskeletal Proteins/metabolism* ; Mice ; Muscle Proteins/metabolism* ; Osteoarthritis/pathology* ; Temporomandibular Joint/pathology*

Background::The calcineurin inhibitor (CNI)-based immune maintenance regimen that is commonly used after renal transplantation has greatly improved early graft survival after transplantation; however, the long-term prognosis of grafts has not been significantly improved. The nephrotoxicity of CNI drugs is one of the main risk factors for the poor long-term prognosis of grafts. Sirolimus (SRL) has been employed as an immunosuppressant in clinical practice for over 20 years and has been found to have no nephrotoxic effects on grafts. Presently, the regimen and timing of SRL application after renal transplantation vary, and clinical data are scarce. Multicenter prospective randomized controlled studies are particularly rare. This study aims to investigate the effects of early conversion to a low-dose CNI combined with SRL on the long-term prognosis of renal transplantation.Methods::Patients who receive four weeks of a standard regimen with CNI + mycophenolic acid (MPA) + glucocorticoid after renal transplantation in multiple transplant centers across China will be included in this study. At week 5, after the operation, patients in the experimental group will receive an additional administration of SRL, a reduction in the CNI drug doses, withdrawal of MPA medication, and maintenance of glucocorticoids. In addition, patients in the control group will receive the maintained standard of care. The patients’ vital signs, routine blood tests, routine urine tests, blood biochemistry, serum creatinine, BK virus (BKV)/cytomegalovirus (CMV), and trough concentrations of CNI drugs and SRL at the baseline and weeks 12, 24, 36, 48, 72, and 104 after conversion will be recorded. Patient survival, graft survival, and estimated glomerular filtration rate will be calculated, and concomitant medications and adverse events will also be recorded.Conclusion::The study data will be utilized to evaluate the efficacy and safety of early conversion to low-dose CNIs combined with SRL in renal transplant patients.Trial registration::Chinese Clinical Trial Registry, ChiCTR1800017277.

Objective:To assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.

Objective: To compare the clinical effects of urokinase thrombolytic therapy for optic artery occlusion (OAO) and retinal artery occlusion (RAO) caused by facial microinjection with hyaluronic acid and spontaneous RAO. Methods: From January 2014 to February 2018, 22 eyes of 22 patients with OAO and RAO caused by facial microinjection of hyaluronic acid who received treatment in Xi'an Fourth Hospital were enrolled in this retrospective study (hyaluronic acid group). Twenty-two eyes of 22 patients with spontaneous RAO were selected as the control group. The BCVA examination was performed using the international standard visual acuity chart, which was converted into logMAR visual acuity. FFA was used to measure arm-retinal circulation time (A-Rct) and filling time of retinal artery and its branches (FT). Meanwhile, MRI examination was performed. There were significant differences in age and FT between the two groups (t=14.840, 3.263; P=0.000, 0.003). The differecens of logMAR visual acuity, onset time and A-Rct were not statistically significant between the two groups (t=0.461, 0.107, 1.101; P=0.647, 0.915, 0.277). All patients underwent urokinase thrombolysis after exclusion of thrombolytic therapy. Among the patients in the hyaluronic acid group and control group, there were 6 patients of retrograde ophthalmic thrombolysis via the superior pulchlear artery, 6 patients of retrograde ophthalmic thrombolysis via the internal carotid artery, and 10 patients of intravenous thrombolysis. FFA was reviewed 24 h after treatment, and A-Rct and FT were recorded. Visual acuity was reviewed 30 days after treatment. The occurrence of adverse reactions during and after treatment were observed. The changes of logMAR visual acuity, A-Rct and FT before and after treatment were compared between the two groups using ttest. Results: At 24 h after treatment, the A-Rct and FT of the hyaluronic acid group were 21.05±3.42 s and 5.05±2.52 s, which were significantly shorter than before treatment (t=4.569, 2.730; P=0.000, 0.000); the A-Rct and FT in the control group were 19.55±4.14 s and 2.55±0.91 s, which were significantly shorter than before treatment (t=4.114, 7.601; P=0.000, 0.000). There was no significant difference in A-Rct between the two groups at 24 h after treatment (t=1.311, P=0.197). The FT difference was statistically significant between the two groups at 24 h after treatment (t=4.382, P=0.000). There was no significant difference in the shortening time of A-Rct and FT between the two groups (t=0.330, 0.510; P=0.743, 0.613). At 30 days after treatment, the logMAR visual acuity in the hyaluronic acid group and the control group were 0.62±0.32 and 0.43±0.17, which were significantly higher than those before treatment (t=2.289, 5.169; P=0.029, 0.000). The difference of logMAR visual acuity between the two groups after treatment was statistically significant (t=2.872, P=0.008). The difference in logMAR visual acuity before and after treatment between the two groups was statistically significant (t=2.239, P=0.025). No ocular or systemic adverse reactions occurred during or after treatment in all patients. Conclusions Urokinase thrombolytic therapy for OAO and RAO caused by facial microinjection with hyaluronic acid and spontaneous RAO is safe and effective, with shortening A-Rct, FT and improving visual acuity. However, the improvement of visual acuity after treatment of OAO and RAO caused by facial microinjection with hyaluronic acid is worse than that of spontaneous RAO.

Objective To assess the occurrence of CNV in patients presenting with flat irregular pigment epithelial detachments (FIPED).Methods Forty-five patients (49 eyes) with FIPED on OCT were enrolled in this retrospective study.There were 25 males (28 eyes) and 20 females (21 eyes).The mean age was 61.022±9.292 years.FFA,ICGA,spectral domain OCT and OCT angiography (OCTA) were performed in all patients during the same period.The FIPED was defined as an irregular elevation of the RPE allowing distinct visualization of Bruch's membrane on OCT B-scan.The abnormal vascular signals from the deep retinal layer to the choroid layer on OCTA was defined as CNV.The CNV was classified into a type 1 CNV and a type 2 CNV according to the OCT characteristics.The CNV was classified into a typical and occult CNV according to the characteristics of the FFA image.Of all 49 eyes,fundus angiography revealed 18 eyes (36.7％) with CNV,and 31 eyes (63.3％) with no characteristic signs of CNV.FFA examination found that CNV in 8 eyes (classic CNV in 1 eyes,occult CNV in 7 eyes),which confirmed by OCT were type 1 CNV;transmitted fluorescence in 41 eyes.ICGA examination showed that CNV-like hyperfluorescence spots in 18 eyes,suspicious hyperfluorescence spots in late stage in 20 eyes,and choroidal high permeability in 11 eyes,respectively;and 18 CNV eyes were confirmed to be type 1 CNV by OCT.To compare the detection of CNV by OCTA and fundus angiography.Results Of the 49 eyes with FIPED,OCTA detected 36 eyes (73.5％) of type 1 CNV,and full or partial strong reflex signals were seen in FIPED;13 eyes (26.5％) were not associated with CNV,and some strong reflection signals were found in FIPED in 9 eyes,4 eyes with weak reflection signal.The FFA was examined for 1,7 eyes of the classic and occult CNV,which confirmed to be type 1 CNV by OCTA.Among the 18 eyes with CNV which detected by ICGA,OCTA also found type 1 CNV.Among the 20 eyes with ICGA's late suspicious strong fluorescent spots,OCTA showed 17 eyes of type 1 CNV;in 11 eyes with high choroidal permeability,OCTA showed type 1 CNV in 1 eye.Among the 36 eyes with CNV which detected by OCT,there were SRD in 32 eyes,no SRD in 2 eyes and retinal interlamellar cavities in 2 eyes.Conclusion OCTA can detect 73.5％ of FIPED eyes with CNV.Compared with traditional fundus angiography,OCTA has a higher detection rate of CNV under FIPED.The FIPED of the internal strong reflection signal has a certain diagnostic value for the type 1 CNV.

Objective? To explore the effects of symposium involving patients and their family members on health education in patients with acute myocardial infarction after percutaneous transluminal coronary intervention (PCI). Methods? Totally 86 patients with acute myocardial infarction receiving PCI in Ningbo First Hospital from January 2017 to June 2018 were selected continuously and divided into the control group (n=43) and the observation group (n=43). Patients in the control group received conventional health education which combined oral education and education manuals, while patients in the observation group symposium-based health education which involved both patients and their family members on the basis of conventional education after PCI. Both groups received health education for 4 weeks. Health knowledge about acute myocardial infarction, rehabilitation initiative, postoperative complication and satisfaction with overall nursing were compared between the two groups before and after intervention. Results? The health-related knowledge of the patients with acute myocardial infarction in the observation group 4 weeks after intervention scored (94.3±4.0), higher than that of the control group, which was (78.4±5.1), and there was statistically significant difference (t=8.285, P＜ 0.05). The scores of five dimensions of rehabilitation initiative (coordination with therapy, compliance, needs for rehabilitation, emotions post frustration and encouragement from family members and nurses) of the observation group were higher than those of the control group (t=4.726, 5.114, 3.975, 7.116, 5.893; P＜0.05). The incidence rate of postoperative complication in the observation group was 9.30%, lower than that of the control group, which was 30.23%, and there was statistically significant difference (χ2=5.939, P＜0.05). The nursing satisfaction of the observation group was 96.73%, higher than that of the control group, which was 83.78%, and there was statistically significant difference (χ2=4.904, P＜0.05). Conclusions? The symposium involving patients and their family members for patients with acute myocardial infarction after PCI can improve the patients' disease-related knowledge, satisfaction with overall nursing and rehabilitation initiative, and reduce the postoperative complications effectively.

Objective: To analyze the quantitative relationship between the number of layers of laser pulses and the amount of step in ultra-short pulse laser cutting of cortical bone, optimize the robot's vertical single stepping parameters, and to explore the feasibility of automatic preparation of dental implant cavity using robot controlling ultra-short pulse laser, in order to lay the foundation for automated dental implant surgery. Methods: Eight pig ribs were segmented into to make 16 specimens. Using the robotic surgical system and path planning software independently developed by our group, circular holes with a diameter of 4 mm were cut two-dimensionally in the rib segments to obtain the quantification relationship of the number of laser pulse layers (n) and the depth of two-dimensional (2D) cutting (d). When conducting the three-dimensional (3D) cutting procedure, the number of pulse layers were set to 5, 10, 15, 20, 25, 30, 35, 40, 45, 50 layers, the vertical single step amount was an integer value corresponding to the results of 2D cutting depth, and the number of pulses (n') corresponding to the minimum difference between the theoretical depth of cut and the actual depth of cut was obtained. The n' was taken as the most suitable single step pulse layer, the rib segment was cut, and the depth of single cut was measured while the integer value was taken as the most appropriate vertical single step amount (d'). The vertical parameters of laser single stepping were set as n' layer pulse and d′ μm step size. The 3D cutting produces a cylindrical cavity with a diameter of 4 mm and a height of 2 mm to evaluate the 3D cutting accuracy (the difference between the measured value and the theoretical value of cutting diameter or depth). Ten 4 mm×3 mm implant holes were automatically prepared on the bilateral femurs of 5 Japanese big white rabbits, and ten 4 mm×3 mm implants made by 3D printer were artificially implanted, and the preparation effect of the implant cavities was evaluated. Results: The quantitative relationship curve between the number of laser pulses (n) and 2D depth of cut (d) showed a linear upward trend. The linear fitting obtained the quantitative relation function formula d=9.278 4 n±26.763 0, R²=0.988 9. The optimum number of single step pulse layers was 5 layers, and the vertical single step amount was 50 μm, so as to set the vertical parameters of a single step of a 3D cutting, and the 3D cutting diameter accuracy was (3.98±2.87) μm, with a depth accuracy of (15.42±5.44) μm. Automated preparation of 10 implant cavities on the femur of the rabbit were completed. When the implants were placed into the implant cavities, there was resistance, but they were fully seated and primary stability has been achieved after seating implant placement. Conclusions The method of non-contact automatic preparation of dental implant cavities using robot controlling ultra-short pulse laser is feasible. By optimizing the single cutting process parameters, precise control of laser cutting cortical bone can be realized.