Establishment of HPLC fingerprint and content determination of multiple index components in Xiao’er resuqing oral liquid / 中国药房

OBJECTIVE To establish an HPLC fingerprint of Xiao’er resuqing oral liquid， and to determine the contents of twelve index components. METHODS HPLC method was adopted. The determination was performed on Venusil MP C18 column with mobile phase consisting of acetonitrile-0.1% phosphate aqueous solution （gradient elution） at a flow rate of 1.0 mL/min. The detection wavelength was set at 210 nm， the column temperature was 30 ℃， the injection volume was 10 μL. HPLC fingerprint of Xiao’er resuqing oral liquid was established by using the Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 edition） to evaluate the similarity. The contents of 12 components were determined， including （R， S）-goitrin， 3，5-O-dicaffeoyl quinic acid， puerarin， forsythin， forsythoside A， chlorogenic acid， baicalin， saikosaponins d， wogonoside， baicalein， emodin and chrysophanol. RESULTS The similarity of HPLC fingerprints of 13 batches of Xiao’er resuqing oral liquid was greater than 0.97， and 14 common peaks were confirmed. The contents of the above 12 index components in 13 batches of Xiao’er resuqing oral liquid were as follows： 0.078-0.172， 1.564-2.736， 1.338-2.578， 0.426-0.872， 1.477-2.628， 1.396-2.447， 4.052-9.146， 0.367- 0.692， 1.974-4.674， 1.274-2.969， 0.085-0.167 and 0.155-0.307 mg/mL. CONCLUSIONS The established HPLC fingerprint and content determination methods have high accuracy and high specificity， which can be used for the quality evaluation of Xiao’er resuqing oral liquid.

Identification of a natural PLA2 inhibitor from the marine fungus Aspergillus sp. c1 for MAFLD treatment that suppressed lipotoxicity by inhibiting the IRE-1α/XBP-1s axis and JNK signaling

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Effect of low concentration of sodium fluoride on osteogenic/odontogenic differentiation of human dental pulp cells / 口腔疾病防治

Objective@#To study the effect of low concentrations of sodium fluoride on the osteogenic/odontogenic differentiation of human dental pulp cells (hDPCs) in vitro.@*Methods@#This study was reviewed and approved by the Ethics Committee. hDPCs were cultured using a modified tissue explant technique in vitro. The effects of different concentrations of sodium fluoride on the proliferation of hDPCs were measured by methylthiazol tetrazolium (MTT) assay. Appropriate concentrations were added to the osteogenic/odontogenic differentiation induction medium, and the cells were induced in vitro. Alizarin red S staining was used to detect the osteoblastic/odontogenic differentiation ability of the cells, and the mRNA expression of the key differentiation factors was detected by RT-qPCR. Moreover, the expression of key molecules of endoplasmic reticulum stress (ERS) was detected by RT-qPCR and Western blot. The data were analyzed with the SPSS 18.0 software package.@*Results@#Low concentration of NaF (0.1 mmol/L) could stimulate cell proliferation in vitro, while a high concentration (5-10 mmol/L) could inhibit cell proliferation (P<0.05). According to the literature and the experimental data, 0.1 mmol/L NaF was selected as the following experimental concentration. The levels of alizarin red S staining were increased after NaF induction of mixed osteogenic/odontogenic differentiation in vitro. The mRNA expression levels of key molecules for osteogenic/odontogenic differentiation, dentin sialophosphoprotein (DSPP), bone sialoprotein (BSP) and osteocalcin (OCN), were increased (P<0.05). The mRNA levels of ERS markers (splicing x-box binding protein-1 (sXBP1), glucose-regulated protein 78 (GRP78) and activating transcription Factor 4 (ATF4) were increased in NaF-treated cells. The protein expression levels of key ER stress molecules (phosphorylated RNA-activated protein kinase-like ER-resident kinase (p-PERK), phosphorylated eukaryotic initiation factor-2α (p-eIF2α) and ATF4) were higher in NaF-treated cells.@*Conclusion@#A low concentration of NaF promotes the osteogenic/odontogenic differentiation of hDPCs and increases the level of ER stress.

Antimicrobial activity of Er, Cr: YSGG and Ultrasonic on E. faecalisbiofilm in the mesial root canal systems of lower molars / Atividade antimicrobiana de Er, Cr: YSGG e Ultrassônico no biofilme de E. faecalis nos sistemas de canais radiculares mesiais de molares inferiores

The internal topography of the root canal is complex, especially for the permanent molar's mesial root. In response to such issues, improved irrigation techniques have been created, which use laser pulses to agitate fluids and improve microbial deposit removal. Objective: To assess the effectiveness of the Er,Cr:YSGG laser with a wavelength of 2,780 nm via photon-induced photoacoustic streaming (PIPS) protocol which agitated of 2% chlorohexidine (CHX) in removing mature Enterococcus faecalis (E. faecalis) biofilm in root canal systems of lower molars. Material and Methods: The mesial roots of lower first and second molars were separated and inoculated with E. faecalis bacterial suspension for 30 days. The roots were irrigated with CHX, some of them were agitated with a passive ultrasonic device (PUI), while the other roots were agitated by an Er,Cr:YSGG laser in PIPS at 60 µs/pulse, 5 Hz, (0.25, 0.5, 0.75, and 1) W. An atomic force microscope (AFM) was used as a new method to get the results in the isthmus area; the obtained results from each group were compared with each other. Results: Based on the AFM and SEM analyses, laser and ultrasonic activation groups showed higher antimicrobial efficacy than the conventional syringe irrigation group (P<0.05). Conclusion: Based on the investigation's findings, the activation of 2% CHX solution by Er,Cr:YSGG laser in PIPS and PUI offers better mature bacterial biofilm removal in the mesial root of lower human molars than the same irrigant with the SI technique (AU)

A topografia interna do canal radicular é complexa, especialmente para a raiz mesial do molar permanente. Em resposta a esses problemas, foram criadas técnicas aprimoradas de irrigação, que utilizam pulsos de laser para agitar fluidos e melhorar a remoção de depósitos microbianos. Objetivo: Avaliar a eficácia do laser Er,Cr:YSGG com comprimento de onda de 2.780 nm via protocolo de streaming fotoacústico induzido por fótons (PIPS) que agitou clorohexidina a 2% (CHX) na remoção de Enterococcus faecalis maduro (E. faecalis) biofilme em sistemas de canais radiculares de molares inferiores. Material e Métodos: As raízes mesiais de 28 primeiros e segundos molares inferiores foram separadas e inoculadas com suspensão bacteriana de E. faecalis por 30 dias. As raízes foram irrigadas com CHX, sendo algumas delas agitadas com aparelho ultrassônico passivo (PUI), enquanto as demais raízes foram agitadas com laser Er,Cr:YSGG em PIPS a 60 µs/pulso, 5 Hz (0,25, 0,5, 0,75 e 1) W. Um microscópio de força atômica (AFM) foi utilizado como um novo método para obter os resultados na área do istmo; os resultados obtidos de cada grupo foram comparados entre si. Resultados: Com base nas análises de AFM e SEM, os grupos de ativação por laser e ultrassom apresentaram maior eficácia antimicrobiana do que o grupo de irrigação com seringa convencional (P<0.05). Conclusão: Com base nos achados da investigação, a ativação da solução de CHX a 2% pelo laser Er,Cr:YSGG em PIPS a (60 µs/pulso, 5 Hz, 0,75 W) oferece melhor remoção de biofilme (AU)

Vascular Endothelial Growth Factor Expression in Breast Carcinoma and its Association with Expression of Estrogen Receptors, Progesterone Receptors and HER-2/neu and Molecular Subtypes

Background: The management of breast carcinoma depends on several molecular markers and tumor stages. In the last decades, estrogen receptors (ER), progesterone receptors (PR), and HER-2/neu have shown good therapeutic responses. Among other molecular markers, vascular endothelial growth factor (VEGF) is becoming more widely used as a prognostic indicator in patients with breast carcinoma. Anti-VEGF therapy already has been proven as an effective chemotherapeutic agent in some other carcinomas. The study aimed to find out the immunohistochemical expression of Vascular Endothelial Growth Factor (VEGF) in breast carcinoma and its possible correlation with the expression of ER, PR, and HER-2/neu and molecular subtypes to evaluate its prognostic value. Material & Methods: This study was conducted in the Department of Pathology, BIRDEM General Hospital, Dhaka, from March 2018 to January 2020. In this study, 45 diagnosed cases of breast carcinoma were enrolled. Slides of all cases were stained with ER, PR, HER-2/neu, and VEGF antibodies following the avidin-biotin-peroxidase staining method. Results: Among 45 cases, 60% showed positive immunohistochemical expression of VEGF. Most of these cases (71.1%) were ER/PR positive. VEGF did not show a significant association with other molecular markers or molecular subtypes. Conclusion: Although, the potential prognostic value of VEGF has not been confirmed. Based on the findings of the current study, it can be assumed that VEGF plays an important role in the pathogenesis of breast cancer. So, it may serve as a useful biomarker for immuno-targeting therapy in patients with breast cancer.

Influence of different surface treatments on bond strength of a Self-Adhesive resin cement to CAD-CAM materials / Influencia de los diferentes tratamientos superficiales en la unión del cemento resinoso autoadhesivo a los materiales CAD-CAM

To evaluate the shear bond strength (SBS) of self-adhesive resin cement when used with two different computer-aided design (CAD)-computer-aided manufacturing (CAM) materials after various surface treatments. Nanoceramic resin Lava Ultimate (LU) and feldspathic ceramic Vita Mark II (VM) CAD-CAM block samples were prepared with 1.5-mm thickness, and a total of 90 samples were obtained (N=90), with five samples of each block. The samples were divided into the following five groups according to the surface treatments (n=9): group 1, untreated (control); group 2,5% hydrofluoric acid etching; group 3, Er: YAG laser irradiation; group 4, tribochemical silica coating (Cojet); and group 5, air-abrasion with Al2O3. After silane application, resin cement was applied on a transparent matrix (diameter, 3mm; height, 2mm) on the blocks. SBS was determined using a universal testing device at a crosshead speed of 1mm/min. Two-way analysis of variance (ANOVA) and Tukey's post hoc tests were used to analyze the SBS values. LU showed the highest SBS value in group 4. The average SBS values in groups 3 and were found to be lower than that in the control group (p<0.05). When VM was examined, while all surface treatments increased the SBS values significantly, the highest SBS value was observed in group 4 (p<0.05). This study revealed that all surface treatments used negatively affected the bond strength values of self-adhesive resin cement to LU, except for Cojet application. The SBS values of resin cement with VM increased in all surface treatment application groups.

Evaluar la resistencia de unión al corte (SBS) del cemento de resina autoadhesivo cuando se utiliza con dos materiales diferentes de diseño asistido por computadora (CAD) y fabricación asistida por computadora (CAM) después de varios tratamientos superficiales. Se prepararon muestras de bloques CAD-CAM de resina Lava Ultimate (LU) y cerámica feldespática Vita Mark II (VM) con un espesor de 1,5mm, y se obtuvieron un total de 90 muestras (N=90), con cinco muestras de cada bloque. Las muestras se dividieron en los siguientes cinco grupos según los tratamientos superficiales (n=9): grupo 1, sin tratar (control); grupo 2, grabado con ácido fluorhídrico al 5%; grupo 3, irradiación con láser Er: YAG; grupo 4, recubrimiento triboquímico de sílice (Cojet); y grupo 5, aire-abrasión con Al2O3. Después de la aplicación de silano, se aplicó cemento de resina sobre una matriz transparente (diámetro, 3mm; altura, 2mm) sobre los bloques. La SBS se determinó usando un dispositivo de prueba universal a una velocidad de cruceta de 1mm/min. Se utilizaron análisis de varianza bidireccional (ANOVA) y pruebas post hoc de Tukey para analizar los valores de SBS. LU mostró el valor más alto de SBS en el grupo 4. Los valores promedio de SBS en los grupos 3 y fueron más bajos que en el grupo de control (p<0,05). Cuando se examinó VM, mientras que todos los tratamientos superficiales aumentaron significativamente los valores de SBS, el valor más alto de SBS se observó en el grupo 4 (p<0,05). Este estudio reveló que todos los tratamientos de superficie utilizados afectaron negativamente los valores de resistencia de la unión del cemento de resina autoadhesivo a LU, a excepción de la aplicación Cojet. Los valores de SBS del cemento de resina con VM aumentaron en todos los grupos de aplicación de tratamiento de superficie.

Enfermedad relacionada con IgG4, enfermedad de Erdheim Chester y compromiso aórtico y/o sus ramas. Diagnóstico diferencial con otras vasculitis de grandes vasos / IgG4 related disease, Erdheim Chester disease and aortic involvement and/or its branches. Differential diagnosis with other large vessel vasculitis

La afección cardiovascular en entidades como Erdheim-Chester (EEC), una rara histiocitosis de células no Langerhans, y la enfermedad relacionada con IgG4 (ER-IgG4), una afección fibrinoinflamatoria inmunomediada, es muy variada y habitualmente asintomática hasta su progresión a daños irreversibles cuando no es sospechada. Ante la dificultad de realizar biopsias por el sitio anatómico, es fundamental valerse de características clínicas, demográficas o imagenológicas que puedan diferenciarlas de otras entidades, como las arteritis de grandes vasos. La población masculina, los mayores de 60 años con compromiso a nivel de la aorta abdominal infrarrenal o aneurismas a nivel de la aorta ascendente con o sin compromiso de otros órganos, son orientativos de ER-IgG4. En la EEC es característico el tejido blando concéntrico que recubre la aorta (aorta recubierta) y sobre todo ante la presencia de fibrosis retroperitoneal, compromiso de huesos largos, hidronefrosis, lesión renal aguda posrrenal e hipertensión arterial, existencia de tejido fibrótico perirrenal, engrosamiento de la fascia renal y tejido adiposo perirrenal (signo del riñón peludo).

Cardiovascular disease in entities such as Erdheim-Chester (ECD), a rare non-Langerhans cell histiocytosis, and IgG4-related disease (ER-IgG4), an immunemediated fibrinoinflammatory disease, is highly varied and usually asymptomatic until it progresses to irreversible damage if they are not taken into account. Given the difficulty of performing biopsies by the anatomical site, it is essential to use clinical, demographic or imaging characteristics that can differentiate them from other entities such as large vessel arteritis. Male population, over 60 years of age with involvement of the infrarenal abdominal aorta or aneurysms at the level of the ascending aorta with or without involvement of other organs, are indicative of ER-IgG4. In ECD, the concentric soft tissue covering the aorta (covered aorta) is characteristic, and especially in the presence of retroperitoneal fibrosis, involvement of long bones, hydronephrosis, post-renal acute kidney injury and arterial hypertension, the presence of perirenal fibrotic tissue, thickening of the renal fascia, perirenal adipose tissue (hairy kidney sign).

Study on the application of model transfer technology in the extraction process of Xiao'er Xiaoji Zhike oral liquid / 药学学报

The modernization and development of traditional Chinese medicine has led to higher standards for the quality of traditional Chinese medicine products. The extraction process is a crucial component of traditional Chinese medicine production, and it directly impacts the final quality of the product. However, the currently relied upon methods for quality assurance of the extraction process, such as simple wet chemical analysis, have several limitations, including time consumption and labor intensity, and do not offer precise control of the extraction process. As a result, there is significant value in incorporating near-infrared spectroscopy (NIRS) in the production process of traditional Chinese medicine to improve the quality control of the final products. In this study, we focused on the extraction process of Xiao'er Xiaoji Zhike oral liquid (XXZOL), using near-infrared spectra collected by both a Fourier transform near-infrared spectrometer and a portable near-infrared spectrometer. We used the concentration of synephrine, a quality control index component specified by the pharmacopoeia, to achieve rapid and accurate detection in the extraction process. Moreover, we developed a model transfer method to facilitate the transfer of models between the two types of near-infrared spectrometers (analytical grade and portable), thus resolving the low resolution, poor performance, and insufficient prediction accuracy issues of portable instruments. Our findings enable the rapid screening and quality analysis of XXZOL onsite, which is significant for quality monitoring during the traditional Chinese medicine production process.

Phosphodiesterase 5 Inhibitors Attenuate Unilateral Ureteral Obstruction-Induced Renal Fibrosis / 中山大学学报(医学科学版)

ObjectiveTo investigate whether phosphodiesterase （PDE） 5 inhibitors sildenafil （SIL） or LW1646 prevented renal interstitial fibrosis induced by unilateral ureteral obstruction （UUO）. MethodsMale C57BL/6 mice were randomly divided into four groups （n =6）， namely the Sham group， 7UUO group， 7UUO+SIL group and 7UUO+LW1646 group. Sildenafil （SIL） or LW1646， or vehicle was administered 1 hour before surgery， and the mice were continuously treated once daily （i. g.， 50 mg/kg） for 7 days. The obstructed kidneys were harvested on day 7. Hematoxylin-eosin （HE） and Masson’s staining was used to examine renal histology. Immunoblotting and RT-qPCR were used to detect the expression levels of protein and mRNA for fibrosis， apoptosis， endoplasmic reticulum （ER） stress， autophagy， and pro-fibrotic factors. Human proximal tubule epithelial cells （HK-2） were treated with TGF-β1 for 48 hours or tunicamycin for 24 hours， respectively， to evaluate whether cyclic guanosine monophosphate （cGMP） or PDE5 inhibitors prevents ER stress and pro-fibrotic responses. ResultsAt the 7th days after UUO， the body weight of the mice showed a significant decrease （P< 0.000 1） compared with that in the sham group. The obstructed kidneys showed a significant tubular dilation and interstitial inflammation. The levels of protein and mRNA expression in apoptosis， ER stress， autophagy-related protein and pro-fibrotic factors were also markedly increased in UUO mice （P <0.05）. In contrast， SIL or LW1646 treatment was associated with attenuated tubular dilation， infiltration of inflammatory cells and collagen content in the obstructed kidney of the mice. The protein and mRNA expression levels of renal TGF-β1 were markedly decreased， and the protein expression levels of apoptosis， endoplasmic reticulum stress， and autophagy markers were also significantly downregulated by PDE5 inhibitors. In HK-2 cells， TGF-β1 induced increased expression levels of fibronectin and BiP， which was at least partially reversed by cGMP， a product of PDE inhibition. Additionally， PDE5 inhibitors were found to modulate aberrant levels of autophagy and apoptosis. ConclusionIn conclusion， PDE5 inhibitors， in particular， LW1646， can alleviate the progression of fibrosis by improving ER stress， apoptosis and autophagy as well as downregulating protein and mRNA expression of TGF-β1.

Research progress of Lycium barbarum polysaccha-ride in preventing and treating Alzheimer's disease / 中国药理学与毒理学杂志

Alzheimer's disease(AD)is a neurode-generative disease with insidious onset and progressive development.In recent years,the prevalence of AD has shown a linear upward trend.At present,its pathogene-sis is not clear.Lycium barbarum polysaccharide(LBP)is one of the main effective components extracted from the dried ripe fruit of Lycium barbarum L.,a solanaceae plant.It has many pharmacological effects such as anti-aging,anti-oxidation,anti-fibrosis,anti-inflammation,neu-roprotection and immunomodulation.LBP has been widely studied in the field of prevention and treatment of AD because of its good anti-aging and neuroprotective effects.Its prevention and treatment mechanism mainly includes the following points:① Regulating the apoptosis of nerve cells.Studies have shown that the signal pathway com-posed of phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)participates in a series of processes such as the growth,proliferation and apoptosis of neurons and plays an important regulatory role.LBP can reduce the number of cell apoptosis,increase the expression levels of autophagy protein Beclin1 and microtubule-associated protein 1 light chain 3Ⅱ(LC3Ⅱ),and decrease the expres-sion levels of p-Akt and phosphorylated mammalian target protein of rapamycin(p-mTOR),which indicates that Lycium barbarum polysaccharide can prevent and treat AD by inhibiting PI3K/Akt/mTOR pathway and improv-ing the autophagy level of cells.②Inhibition of amyloid β-protein(Aβ)production.Aβ is the main component of senile plaque,which is regarded as the main biomarker of AD.It is found that the neurotoxicity of Aβ plays a role by increas-ing the influx of Ca2+ mediated by N-methyl-D-aspartate receptor in the process of signal transduction in the brain,and then generating reactive oxygen species(ROS)and apoptosis signals.LBP can promote autophagy of HT22 cells by inhibiting PI3K/Akt pathway,which has a protec-tive effect on Aβ-induced toxicity.③ Inhibit the produc-tion of inflammatory cytokines.In the pathogenesis of AD,microglia are activated when they feel pathological accumulation of Aβ,and then cell surface immune and adhesion molecules such as cluster of differentiation 45(CD45),CD40,CD36 and integrins are activated,thereby recruiting Src family kinases and activating MAPK path-way,leading to over-expression of proinflammatory fac-tors.A large number of cytokines and chemokines are produced,which may lead to synapse damage and loss.For example tumor necrosis factor-α(TNF-α)can induce neuronal apoptosis and injury.The production of interleu-kin,and other cytokines and chemokines may also lead to microglia activation,astrocyte proliferation,and further secretion of proinflammatory factors and amyloid deposi-tion,thus making the neuroinflammatory cascade perma-nent.LBP can down-regulate the expression of TNF-α and IL-1β genes,reduce the level of intracellular ROS,and improve the learning and memory ability of AD patients.In this paper,the mechanism of Lycium barbarum polysaccharide in preventing and treating AD is reviewed,in order to provide basis for drug development and clini-cal application.

Effect of dual wavelength laser in the treatment of chronic periodontitis and the influence of cytokines in gingival crevicular fluid / 中国医师进修杂志

Objective:To investigate the clinical efficacy and prognostic factors of Neodymium doped: Yttrium Aluminum Garnet (Nd:YAG ) laser combined with Erbium:Yttrium Aluminum Garnet (Er:YAG) laser assisted subgingival scaling root planing (SRP) in the treatment of periodontitis.Methods:A prospective research method was adopted. A total of 66 patients with periodontitis treated in Hebei Chest Hospital from August 2018 to August 2020 were selected and divided into experimental group and control group according to the random number table method, with 33 cases in each group. The control group was treated with SRP, and the experimental group received Er:YAG laser curettage combined with root surface leveling on the basis of SRP, and irradiated the periodontal pocket with Nd:YAG laser. The changes of periodontal clinical indicators and cytokine levels in gingival crevicular fluid were examined before treatment, 4 weeks and 12 weeks after treatment. The patients were divided into PD<3 mm group and PD ≥ 3 mm group according to the probing depth (PD) of periodontal pocket after 12 weeks of treatment, the clinical data of the two groups were compared and analyzed, and the Logistic regression analysis was performed to analyze the risk factors affecting the prognosis of patients with periodontitis after laser treatment.Results:After 4 and 12 weeks of treatment, the PD, clinical attachment loss (CAL), sulcus bleeding index (SBI) and plaque index (PLI) of the two groups were significantly lower than those before treatment ( P<0.05), and the PD, CAL, SBI and PLI in experimental group were significantly lower than those in control group, after 4 weeks of treatment: (3.36 ± 0.21) mm vs. (3.91 ± 0.39) mm, (4.14 ± 0.67) mm vs. (4.75 ± 0.73) mm, (1.83 ± 0.20) scores vs. (2.58 ± 0.17) scores, (1.29 ± 0.24) scores vs. (1.61 ± 0.52) scores; after 12 weeks of treatment: (3.04 ± 0.28) mm vs. (3.66 ± 0.54) mm, (3.91 ± 0.47) mm vs. (4.68 ± 0.66) mm, (0.88 ± 0.06) scores vs. (1.35 ± 0.14) scores, (1.05 ± 0.31) scores vs. (1.57 ± 0.56) scores, the differences were statistically significant ( P<0.05). After 12 weeks of treatment, the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-8 (MMP-8) and interleukin-1β (IL-1β) in gingival crevicular fluid in experimental group were significantly decreased compared with those in control group: (2.95 ± 0.19) μg/L vs. (4.32 ± 0.84) μg/L, (2.63 ± 0.82) μg/L vs. (3.58 ± 0.51) μg/L, (12.42 ± 1.19) μg/L vs. (13.26 ± 0.68) μg/L, (4.15 ± 1.12) ng/L vs. (5.36 ± 0.42) ng/L, (2.65 ± 0.08) ng/L vs. (4.12 ± 0.19) ng/L, the differences were statistically significant ( P<0.05), while the level of transforming growth factor-β (TGF-β) was significantly increased compared with that in control group: (51.35 ± 8.95) ng/L vs. (44.90 ± 5.84) ng/L, and the differences between the groups were statistically significant ( P<0.05). Logistic regression analysis showed that the clinical indexes PD, SBI, PLI, IL-6, IL-8, TNF- α, MMP-8, IL-1β and crown root ratio of gingival crevicular fluid were all the risk factors for prognosis of periodontitis treated with dual wavelength laser ( P<0.05). Conclusions:Nd:YAG laser combined with Er:YAG laser assisted SRP can obtain good curative effect in the treatment of periodontitis. Periodontal clinical indexes PD, SBI, PLI, gingival crevicular fluid IL-6, IL-8 and TNF-α, MMP-8, IL-1β level and crown root ratio were independent risk factors for the prognosis of periodontitis treated with dual wavelength laser.

Translocation of IGF-1R in endoplasmic reticulum enhances SERCA2 activity to trigger Ca2+ER perturbation in hepatocellular carcinoma

The well-known insulin-like growth factor 1 (IGF1)/IGF-1 receptor (IGF-1R) signaling pathway is overexpressed in many tumors, and is thus an attractive target for cancer treatment. However, results have often been disappointing due to crosstalk with other signals. Here, we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma (HCC) cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2) activity. In response to ligand binding, IGF-1Rβ is translocated into the ER by β-arrestin2 (β-arr2). Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rβ. SERCA2 activity is heavily dependent on the increase in ER IGF-1Rβ levels. ER IGF-1Rβ phosphorylates SERCA2 on Tyr990 to enhance its activity. Mutation of SERCA2-Tyr990 disrupted the interaction of ER IGF-1Rβ with SERCA2, and therefore ER IGF-1Rβ failed to promote SERCA2 activity. The enhancement of SERCA2 activity triggered Ca2+ER perturbation, leading to an increase in autophagy. Thapsigargin blocked the interaction between SERCA2 and ER IGF-1Rβ and therefore SERCA2 activity, resulting in inhibition of HCC growth. In conclusion, the translocation of IGF-1R into the ER triggers Ca2+ER perturbation by enhancing SERCA2 activity through phosphorylating Tyr990 in HCC.

The removal of three kinds of occlusal veneers by Er: Yag laser / 华西口腔医学杂志

OBJECTIVES@#This study aimed to remove occlusal veneers of varied thicknesses and compositions by Er:Yag laser in vitro and analyze the interfacial microstructure between veneers and tooth that irradiated by laser, by which experimental evidence could be provided to support the non-invasive removal of occlusal veneerby laser.@*METHODS@#Fresh mandibular premolars extracted for orthodontic requirements were collected for tooth preparation. Three kinds of ceramic materials (Vita Suprinity, Vita Mark Ⅱ, and Upcera Hyramic) were selected to fabricate occlusal veneer with different thicknesses (1.0, 1.5, and 2.0 mm). One week later, Er:Yag laser (2.5 W and 3.5 W) was used to irradiate and remove the occlusal veneer and recorded the timespan. After the removal operation, the micro-morphologies of samples were examined by scanning electron microscope.@*RESULTS@#Upcera Hyramic veneer failed to be removed (>20 min); the operation span at 2.5 W, Vita Suprinity (96.0 s±16.0 s) was longer than Vita MarkⅡ(84.5 s±19.5 s) in the 1.0 mm group (P<0.05), and Vita Suprinity (246.5 s±13.5 s) was longer than Vita MarkⅡ(170.0 s±14.0 s) in the 1.5 mm group (P<0.05). At 3.5 W, Vita Suprinity (381.0 s±24.0 s) was longer than Vita MarkⅡ(341.5 s±26.5 s) in the 2.0 mm group.@*CONCLUSIONS@#Increasing laser power could shorten the operation span and facilitate the removal of occlusal veneers with the same thickness and composition. The occlusal veneer was sustained when insufficient laser power was applied. With the same laser power and ceramic thickness, laser penetration could interfere with the integral of the ceramic structure when the laser interacted with the bonding layer. With the same ceramic composition and laser power, the operation span and laser power increased with the thickness of the occlusal veneer. However, the laser was incapable of removing occlusal resin veneer directly.

Comparison of four methods that remove calcium hydroxide from root canals / 口腔疾病防治

Objective@# To compare the efficiency of four methods that remove calcium hydroxide in root canals and to guide clinical practice. @* Methods @# Sixty-five isolated mandibular single root canal premolars were collected. After crown cutting and root canal preparation, a tooth was randomly selected as the blank control group, and the remaining 64 teeth were equally divided into Groups A and B (n = 32). Group A was injected with water-soluble calcium hydroxide, and Group B was injected with oil-soluble calcium hydroxide. After 2 weeks of drug sealing, Groups A and B were randomly divided into 4 groups (n = 8), including the lateral opening syringe group, sonic vibration group, ultrasonic group, and Er: YAG laser group. Before and after calcium hydroxide removal, the samples were scanned by cone-beam CT, and the data were imported into Mimics for 3D reconstruction. The root canal was divided into the following segments: superior root segment, middle and apical, and the calcium hydroxide volume of each segment of the root canal was calculated. The volumes of calcium hydroxide before and after removal were V1 and V2, respectively, with a clearance rate = (V1-V2)/V1×100%. Three-factor ANOVA was used for statistical analysis. After Groups A and B were reconstructed, the apical region with residual calcium hydroxide was selected, and the blank control was observed by scanning electron microscopy (SEM). @*Results @# Two types of calcium hydroxide could not be completely removed by the four flushing methods. The clearance rate of water-soluble calcium hydroxide was higher than that of oil-soluble calcium hydroxide (P<0.001). Among the three segments of the root canal, the clearance rate of the apical segment was lower (P<0.05). The Er: YAG laser treatment group showed the highest removal efficiency of two kinds of calcium hydroxide, which was higher than that of the other groups, especially in apical of the root. Compared with the sonic wave washing group and the syringe washing group, the ultrasonic wave washing group exhibited significant advantages (P<0.05). The clearance rate of the sonic wave washing group was higher in the oily calcium hydroxide root middle group than in the syringe washing group (P<0.05). SEM showed that the two kinds of calcium hydroxide could not be completely removed, but the residual rate of oil-soluble calcium hydroxide was large.@*Conclusion @# Both types of calcium hydroxide could not be completely removed, and compared to water-soluble calcium hydroxide, oil-soluble calcium hydroxide was more difficult to remove. Among the four cleaning methods, Er:YAG laser swing washing showed the higher cleaning efficiency.

Quality evaluation of Qilong Zhuang'er oral liquid based on UHPLC-Q-exactive orbitrap MS and chemometrics analysis / 药学学报

An UHPLC-Q-exactive orbitrap MS method for the simultaneous determination of 19 chemical components in Qilong Zhuang'er oral liquid was established and the quality differences between different batches of samples was compared by chemometric analysis to provide a basis for the quality evaluation of the preparation. The contents of allantoin, L-proline, pyroglutamic acid, hordenine, adenosine, L-phenylalanine, guanosine, L-tryptophan, caffeic acid, calycosin-7-glucoside, verbascoside, isoacteoside, ononin, calycosin, 3-hydroxy-9,10-dimethoxyptercarpan, formononetin, atractylenolide III, atractylenolide II and astragaloside A were analyzed by cluster heat map, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) using Hiplot platform and MarkerlynxXS software to comprehensively evaluate the quality difference of different batches of Qilong Zhuang'er oral liquid. The 19 chemical compounds showed good linearity in their respective concentration ranges (r ≥ 0.999). The RSD of precision, repeatability and stability (24 h) tests were all less than 1.94%. The average recovery was 97.24%-102.75% (RSD < 2.74%, n = 6). The 10 batches of samples were divided into two categories by cluster heat map and PCA analysis. 3-Hydroxy-9,10-dimethoxyptercarpan, atractylenolide III, calycosin, atractylenolide II, formononetin, allantoin and caffeic acid were identified as differential markers by PLS-DA. The established multi component quantitative method of Qilong Zhuang'er oral liquid combined with chemometric analysis can provide reference for the quality evaluation of the preparation.

The penetration effect of ultrasound and Er:YAG laser irrigation activation techniques on dentine of infected human root canals / 口腔疾病防治

Objective@#This ex vivo study evaluated the effect of ultrasound and Er:YAG laser irrigation activation techniques on the penetration of sodium hypochlorite solution into infected human root canal dentin, providing a reference for clinical infection control of infected root canals.@*Methods @#Thirty-six cases of infected root canals were collected and randomly divided into three groups according to the irrigation technique: 12 cases in the conventional syringe irrigation (CSI) group, 12 cases in the passive ultrasonic irrigation (PUI) group, 12 cases in the Er:YAG laser and photon-induced photoacoustic streaming (PIPS) group and 36 cases of clean root canals (12 cases in the CSI group, 12 cases in the PUI group, 12 cases in the PIPS group). All of the selected root canals were straight root canals of posterior teeth. After standardizing the root length, all canals were subjected to instrumentation and dynamic irrigation. 2% methylene blue solution was used to visualize the penetration of the irrigant. EXAKT cutting and grinding equipment was used to take transverse sections of 100-150 μm at the coronal, middle and apical thirds of the root canals. The data (maximum penetration depth, average penetration depth, and penetration percentage) were observed under a light microscope to evaluate the effect of dye penetration. @*Results @# With the three irrigation techniques, the maximum penetration depth, average penetration depth and penetration percentage of the infected root canals were significantly lower than those of clean root canals in the full length of the root canal (P<0.05). The penetration percentage, average penetration depth and maximum penetration depth of the PIPS group were significantly higher than those of the CSI group in the coronal, middle and apical thirds of the infected root canal, respectively (P<0.05). There was no significant difference in the maximum penetration depth, average penetration depth or penetration percentage between the PUI and CSI groups (P>0.05). There was also no significant difference in the maximum penetration depth, average penetration depth or penetration percentage between the PIPS and PUI groups (P>0.05). @*Conclusion @# The dentine permeability of infected root canals was weaker than that of clean root canals. Er:YAG laser-assisted irrigation activation technology could significantly improve the penetration of sodium hypochlorite solution into infected dentin, but passive ultrasonic irrigation did not significantly improve the penetration.

A novel defined risk signature of endoplasmic reticulum stress-related genes for predicting the prognosis and immune infiltration status of ovarian cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Endoplasmic reticulum (ER) stress, as an emerging hallmark feature of cancer, has a considerable impact on cell proliferation, metastasis, invasion, and chemotherapy resistance. Ovarian cancer (OvCa) is one of the leading causes of cancer-related mortality across the world due to the late stage of disease at diagnosis. Studies have explored the influence of ER stress on OvCa in recent years, while the predictive role of ER stress-related genes in OvCa prognosis remains unexplored. Here, we enrolled 552 cases of ER stress-related genes involved in OvCa from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts for the screening of prognosis-related genes. The least absolute shrinkage and selection operator (LASSO) regression was applied to establish an ER stress-related risk signature based on the TCGA cohort. A seven-gene signature revealed a favorable predictive efficacy for the TCGA, International Cancer Genome Consortium (ICGC), and another GEO cohort (P<0.001, P<0.001, and P=0.04, respectively). Moreover, functional annotation indicated that this signature was enriched in cellular response and senescence, cytokines interaction, as well as multiple immune-associated terms. The immune infiltration profiles further delineated an immunologic unresponsive status in the high-risk group. In conclusion, ER stress-related genes are vital factors predicting the prognosis of OvCa, and possess great application potential in the clinic.

Effect of cavity disinfection protocols on microtensile bond strength of universal adhesive to dentin / Efecto de los protocolos de desinfección de cavidades en la fuerza de adhesión microtensil del adhesivo universal a la dentina

Abstract The purpose of this study was to compare the effect of different disinfection protocols of dentin on bond strength of an MDP-containing universal adhesive. Twelve extracted mandibular third molars were separated horizontally at the mid-coronal of crown to get smooth and sound dentin surfaces using low-speed diamond saw. The teeth were randomly fallen into four groups: chlorhexidine (CHX), ozone, Er,Cr:YSGG laser irradiation (LASER) and no treatment (control). After cavity disinfection application, a universal adhesive (G-Premio Bond) was applied to the surface of dentin according to self-etch mode as instructed by the manufacturer. After incremental built-up of composite resin (Charisma Smart), the specimens were immersed in distilled water at 37°C for 24h. Dentin/composite beams with 1 mm² cross sectional area were produced and micro-tensile bond strength (µTBS) was applied on these beams (n=20). Failure mods were determined under a stereomicroscope at ×40. The resin penetration of samples stained with Rhodamine B fluorochrome dye was examined with a confocal laser scanning microscope. Statistical analysis was performed with SPSS-22. Test results were analyzed using One-way Anova and Tukey HSD Post-Hoc tests (p0.5). All applications of cavity disinfection procedures decreased the µTBS of the resin-dentin interface.

Resumen El propósito de este estudio fue comparar el efecto de diferentes protocolos de desinfección de la dentina sobre la fuerza de unión de un adhesivo universal que contiene MDP. Doce terceros molares mandibulares extraídos se quebraron horizontalmente en la mitad de la corona para obtener superficies de dentina lisas y sólidas utilizando una sierra de diamante de baja velocidad. Los dientes se dividieron aleatoriamente en cuatro grupos: clorhexidina (CHX), ozono, irradiación con láser Er,Cr:YSGG (LASER) y ningún tratamiento (control). Después de la aplicación de la desinfección de la cavidad, se aplicó un adhesivo universal (G-Premio Bond) a la superficie de la dentina según el modo de autograbado indicado por el fabricante. Después de la obturación con resina compuesta (Charisma Smart), las muestras se sumergieron en agua destilada a 37°C durante 24h. Se produjeron porciones de dentina/resina con un área de sección transversal de 1 mm² y se aplicó una fuerza de adhesión microtensile (µTBS) (n=20). Los modos de falla se determinaron bajo un microscopio estereoscópico a ×40. La penetración de la resina de las muestras teñidas con colorante fluorocromo rodamina B se examinó con un microscopio de barrido láser confocal. El análisis estadístico se realizó con SPSS-22. Los resultados de las pruebas se analizaron utilizando las pruebas post-hoc Anova unidireccional y Tukey HSD (p0.5). Todas las aplicaciones de procedimientos de desinfección de cavidades redujeron el µTBS de la interfaz resina-dentina.

Comparações do desempenho social de crianças submetidas à intervenção musicoterapêutica: estudo piloto / Comparisons of the social performance score of children undergoing music therapy intervention: pilot study / Comparaciones de la puntuación de desempeño social de los niños sometidos a una intervención de musicoterapia: estudio piloto

Este estudo comparou medidas de desempenho social em crianças integrantes de um programa de intervenção musicoterapêutica. Participaram sete crianças de idades entre sete a nove anos, sendo seis meninos e uma menina, e também seus pais. Os instrumentos utilizados foram SSRS para avaliar habilidades sociais e IMTAP, apenas o domínio social. Os resultados não apontaram diferenças estatisticamente significativas entre as medidas avaliadas. Na reavaliação houve aumento nos escores pela IMTAP, já pelo SSRS houve diminuição nas habilidades sociais nas duas versões - crianças e pais, além de aumento nos escores dos comportamentos problemáticos. O relato dos pais indicou melhorias na emissão de comportamentos sociais adequados.

This study compared measures of social performance in children participating in a music therapy intervention program. Seven children aged between seven and nine years participated, six boys and one girl, as well as their parents. The instruments used were SSRS to assess social skills and IMTAP, only the social domain. The results did not show statistically significant differences between the measures evaluated. In the reassessment there was an increase in the scores by the IMTAP, on the other hand by the SSRS, there was a decrease in social skills in both versions - children and parents, in addition to an increase in scores problematic behavior. The parents' report indicated improvements in the emission of appropriate social behaviors.

Este trabajo comparó medidas de desempeño social em niños participaron em un programa de intervención de musicoterapia. Participaron siete niños de entre siete y nueve años, siendo seis niños y una niña, así como sus padres. Los instrumentos utilizados fueron SSRS para evaluar habilidades sociales e IMTAP, solo el dominio social. Los resultados no apuntaran a diferencias estadísticamente significativas entre las medidas evaluadas. En la reevaluación, hubo un aumento em los puntajes por el IMTAP, por otro lado, por el SSRS, hubo una disminución en las habilidades sociales en ambas versiones, niños y padres, además de un aumento en los puntajes de comportamientos problemáticos. El informe de los padres indicó mejoras en la emisión de conductas sociales adecuadas.

Transcriptome Analysis of Entamoeba histolytica Trophozoites during in vivo Contact-independent Mediated Host-parasite Interaction: Putative Pathways Related to PCD

Aim: In the present study, we exploited DNA microarray-based transcriptome analysis and showed overall changes in gene expression in vivo of amoebic trophozoites that interact with animal soluble factors using an intraperitoneal dialysis bag model to elucidate putative molecular pathways and genes involved in this interaction. Study Design: We exploited DNA microarray-based transcriptome analysis. Results: An analysis from a network including the interactions of up-regulated genes and their neighbors revealed the presence of 11 functionally related modules. Six of the modules obtained were related to endoplasmic reticulum (ER) functions, such as degradation, stress, proteasome-ubiquitination, phosphorylation, lipid metabolism, and protein sorting. Furthermore, major transcriptional changes displayed by the parasite at the beginning of interaction were attributed to the response to the host defense. These data are consistent with the notion that the concerted expression of genes necessary for survival such as increment in protein synthesis, cytoskeleton rearrangement, vesicular traffic and genes involved in cell death including calcium imbalance and the ER signals associated with protein degradation (ERAD) is an overall landscape during the in vivo interaction between the amoebic trophozoites and animal soluble factors, and suggest that the ER stress is one of the main pathways leading to programmed cell death in E. histolytica. Conclusion: The present findings on the global transcriptional changes displayed by the parasite at the early stages of interaction with host environments in peritoneal implantation indicate that a substantial proportion of concerted changes in gene expression in amoebic trophozoites are attributable to the parasite’s response for cell death signals due to ER stress. A detailed knowledge of the underlying molecular mechanism might suggest the efficient elimination of this parasite by promoting their death pathways.