BACKGROUND:Leonurine has many biological activities such as improving microcirculation,anti-oxidation,anti-apoptosis,scavenging free radicals,anti-inflammation,and anti-fibrosis,and can promote osteogenic differentiation of bone marrow mesenchymal stem cells,which has the potential to be applied in the treatment of periodontitis. OBJECTIVE:To explore the anti-inflammatory and osteogenic effects of leonurine loading into chitosan/sodium glycerophosphate/sodium alginate hydrogel. METHODS:(1)Chitosan/sodium glycerophosphate/sodium alginate hydrogel(blank hydrogel)and chitosan/sodium glycerophosphate/sodium alginate/leonurus alkali hydrogel were prepared respectively.RAW 264.7 and MC3T3-E1 cells were inoculated with the two kinds of hydrogel.The cytotoxicity of hydrogels was detected by CCK-8 assay and live/dead cell staining.(2)RAW 264.7 cells were cultured in five groups.The blank group was cultured for 24 hours routinely.The lipopolysaccharide group was treated with lipopolysaccharide.The simple hydrogel group was treated with lipopolysaccharide and blank hydrogel.The drug-loaded hydrogel group was treated with lipopolysaccharide and drug-loaded hydrogel.The inhibitor group was treated with lippolysaccharide,drug-loaded hydrogel,and PI3K inhibitor LY294002.24 hours later,mRNA expression of inflammation-related factors was detected by qRT-PCR.Western blot assay was utilized to detect the protein expression of inflammation-related factors and PI3K/AKT signaling pathway.(3)MC3T3-E1 cells were inoculated in four groups.The blank group was cultured without any material.The simple hydrogel group was treated with blank hydrogel.The drug-loaded hydrogel group was treated with drug-loaded hydrogel.The inhibitor group was treated with drug-loaded hydrogel and PI3K inhibitor LY294002 for 7 days.Alkaline phosphatase staining was performed.mRNA expression levels of osteogenic factors were detected by qRT-PCR.The protein expression levels of the PI3K/AKT signaling pathway were detected by western blot assay. RESULTS AND CONCLUSION:(1)The results of CCK-8 assay and live/dead cell staining showed that the two kinds of hydrogels had no cytotoxic effect and had good cytocompatibility.(2)Compared with the blank group,the mRNA and protein expression levels of interleukin 6,tumor necrosis factor α,and interleukin 1β were significantly increased(P<0.05),and the protein expression levels of p-AKT,p-PI3K,p-p65,and p-IκBα were significantly increased in the lipopolysaccharide group(P<0.05).Compared with lipopolysaccharide group,mRNA and protein expression levels of the above indexes were decreased in drug-loaded hydrogel group(P<0.05).Compared with the drug-loaded hydrogel group,the mRNA and protein expression levels of the above indexes were decreased in the inhibitor group(P<0.05).(3)The activity of alkaline phosphatase in drug-loaded hydrogel group was higher than that in the blank group,simple hydrogel group,and inhibitor group(P<0.05).Compared with blank group,the mRNA expression levels of alkaline phosphatase,Runx2,osteocalcin,and type I collagen were increased(P<0.05),and the protein expression levels of p-AKT and p-PI3K were increased in the simple hydrogel group(P<0.05).Compared with the simple hydrogel group,the mRNA and protein expression levels of the above indexes were increased in the drug-loaded hydrogel group(P<0.05).Compared with the drug-loaded hydrogel group,the mRNA and protein expression levels of the above indexes were decreased in the inhibitor group(P<0.05).(4)These findings conclude that chitosan/sodium glycerophosphate/sodium alginate/leonurine hydrogel has anti-inflammatory and osteogenic effects,which may be related to the regulation of PI3K/AKT signaling pathway.

Objective:To understand and explore the incidence and influencing factors of malnutrition in patients with inflammatory bowel disease.Methods:This study was a cross-sectional study. Patients with inflammatory bowel disease hospitalized in the Department of Gastroenterology of a tertiary hospital in Shenzhen from March 1 to August 31, 2021 were enrolled. Indicators related to nutrition and clinical outcome were collected, including height, weight, body mass index (BMI), nutritional risk screening (NRS 2002) results, malnutrition diagnosis as per Global Leadership Initiative on Malnutrition (GLIM) criteria and Pittsburgh Sleep Quality Index (PSQI). Chi-square test, t-test and Wilcoxon rank sum test were used as appropriate for univariate analysis, and binary logistic regression analysis was used for multivariate analysis.Results:A total of 188 patients were included in this survey. There were 145 (77.1%) patients with no malnutrition, 38 (20.2%) with moderate malnutrition, and 5 (2.7%) with severe malnutrition according to GLIM criteria. In the subgroup of 47 ulcerative colitis patients, 12 (25.5%) were with moderate malnutrition and 3 (3.4%) were with severe malnutrition. In the subgroup of 141 Crohn's disease patients, 26 (18.4%) were with moderate malnutrition and 2 (1.4%) were with severe malnutrition. When divided by the presence or absence of malnutrition, there were statistically significant differences in age ( t = -2.237, P = 0.026), disease stage ( χ 2 = 22.299, P < 0.001), history of digestive tract resection ( χ 2 = 6.890, P = 0.009), intestinal infection ( χ 2 = 4.010, P = 0.045), gastrointestinal symptoms ( χ 2 =11.884, P = 0.001), hemoglobin ( t = 5.160, P < 0.001), serum albumin ( t = 3.96, P < 0.001), prealbumin ( t = 5.061, P < 0.001) and PSQI scores ( t = -4.744, P < 0.001). Multivariate analysis showed that the stage of disease, history of partial resection of digestive tract, gastrointestinal symptoms, hemoglobin, prealbumin and PSQI scores were the main influencing factors of malnutrition. Conclusions:IBD patients at older age, at active stage, and with history of partial digestive tract resection, intestinal infection, gastrointestinal symptoms, low hemoglobin, low serum albumin, low prealbumin and poor sleep quality are more likely to develop malnutrition. Timely intervention should be carried out to improve the nutritional status of these patients.

Anaplastic lymphoma kinase (ALK) fusions represent the second most common oncogenic driver mutation in non-small cell lung cancer (NSCLC). As the new class of 3rd generation of ALK tyrosine kinase inhibitor (TKI), lorlatinib has shown robust potency and brain-penetrant clinical activity against a wide spectrum of multiple resistance mutations within the ALK domain detected during crizotinib and 2nd generation ALK TKI treatment. Lorlatinib is generally well-tolerated with unique adverse drug reaction/adverse event, including hyperlipidemia and central nervous system effects, which are mostly mild to moderate severity and manageable through dosage modifications and/or standard medical intervention. For advanced NSCLC with ALK positivity, patients should be evaluated for baseline characteristics and pre-existing medication, informed of the potential toxicities, and periodically monitored to balance benefits and risks. Moreover, a multidisciplinary group of experts is essential to establish a comprehensive diagnostic and therapeutic strategy.
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Aminopyridines ; Carcinoma, Non-Small-Cell Lung/pathology* ; China ; Consensus ; Drug Resistance, Neoplasm/genetics* ; Drug-Related Side Effects and Adverse Reactions/drug therapy* ; Humans ; Lactams ; Lactams, Macrocyclic/adverse effects* ; Lung Neoplasms/pathology* ; Protein Kinase Inhibitors/adverse effects* ; Protein-Tyrosine Kinases/genetics* ; Pyrazoles

Objective To evaluate the role of pl20-catenin protein (p120) in mechanical stretchinduced transferring of E-cadherin to cytoplasm in mouse alveolar epithelial cells.Methods Experiment Ⅰ Mouse alveolar epithelial cells (MLE-12 cells) were seeded in 6-well cell stretch plates at a density of (1.0-1.5) ×106 cells/well and divided into 3 groups (n=12 each) using a random number table:control group (group C),cyclic stretch for 2 h group (group CS2) and cyclic stretch for 4 h group (group CS4).The cells underwent 20％ cyclic stretch at 0.5 Hz (stretch:intermittence =1 ∶ 1) for 2 and 4 h in CS2 and CS4 groups,respectively.The cells underwent no cyclic stretch in group C.The expression of p120,E-cadherin and phosphorylated Src kinase (p-Src) and expression of E-cadherin in cytomembrane and cytoplasma were detected by Western blot.Experiment Ⅱ MLE-12 cells were seeded in 6-well cell stretch plates at a density of (1.0-1.5)× 106 cells/well and divided into 4 groups (n =6 each) using a random number table:control group (group C),cyclic stretch group (group CS),p120 small interfering RNA (siRNA) transfection group (group p120 siRNA),and p120 siRNA transfection plus cyclic stretch group (group p120 siRNA+CS).The cells were transfected with scramble siRNA in C and CS groups,and 24 h later the cells underwent 20％ cyclic stretch for 2 h at 0.5 Hz (stretch:intermittence =1 ∶ 1) in group CS.The cells were transfected with p120 siRNA in p120 siRNA and p120 siRNA+CS groups,and 24 h later the cells underwent 20％ cyclic stretch for 2 h at 0.5 Hz (stretch ∶ intermittence =1 ∶ 1) in group p120 siRNA+CS.The expression of E-cadherin in cytomembrane and cytoplasm was detected by Western blot after the end of treatment in each group.Results Experiment Ⅰ Compared with group C,the expression of p120 and E-cadherin was significantly down-regulated,the expression of p-Src was up-regulated,the expression of E-cadherin in cytomembrane was down-regulated,and the expression of E-cadherin in cytoplasm was up-regulated in CS2 and CS4 groups (P ＜ 0.05).Compared with group CS2,the expression of p120 and E-cadherin was significantly down-regulated,the expression of p-Src was up-regulated,the expression of E-cadherin in cytomembrane was down-regulated,and the expression of E-cadherin in cytoplasm was upregulated in group CS4 (P ＜ O.05).Experiment Ⅱ Compared with group C,the expression of E-cadherin in cytomembrane was significantly down-regulated,and the expression of E-cadherin in cytoplasm was up-regulated in CS,p120 siRNA and p120 siRNA+CS groups (P＜ 0.05).Compared with group CS or group p120 siRNA,the expression of E-cadherin in cytomembrane was significantly down-regulated,and the expression of E-cadherin in cytoplasm was up-regulated in group p120 siRNA+CS (P＜0.05).Conclusion The degradation of p120 can promote mechanical stretch-induced transferring of E-cadherin to cytoplasm in mouse alveolar epithelial cells.

Objective:To compare the alveolar cortical bone density and thickness of jaw bones between teenagers (12-18 years of age) and adults(19-48 years of age).Methods:Spiral computed tomographic images of 60 cases were obtained from the subjects with the ages of 12 to 48 years(27 Males and 33 females,35 teenagers and 25 adults).Buccal cortical bone thickness and density in Hounsfield units were measured at 12 interradicular sites and to a depth of 14 mm.Results:The alveolar cortical bone thicknesses and densities of the jaw bones significantly increased from the crest to base of alveolar crest.The average cortical bone thicknesses rangedfrom 1.0 to 1.5 mm in the anterior part of the jaw bones,1.1 to 1.8 mm in maxillary posterior area and 1.5 to 2.8 mm in the mandible posterior areas.The cortical bone thickness and density were greater in the mandible than in the maxilla(P ＜ 0.05).The thickness values did not show difference between males and females,between adolescents and adults.Higher values of bone density were found in the adults than in the teenagers(P ＜0.05).The highest bone density in the mandible posterior area of adults was observed,and the lowest bone density in the maxillary posterior area of adolescents.Conclusion:Alveolar cortical bone density of adolescents is lower than that of adults,especially in the maxilla posterior region.

BACKGROUND:Diameter and length of mini-implant have effects on its stability, which has been reported mostly in I and II osteoid, but less in IV osteoid. OBJECTIVE:To optimize the design of mini-implant diameter and length in IV osteoid by a three-dimensional finite element analysis. METHODS:Implant-mandible solid model was established. A 2 N orthodontic force that was perpendicular to the long axis of the implant and at a 30° angle with the distal central axis was applied onto the top of the implant. The implant was designed for different diameters (1.2-2.0 mm) and lengths (6-10 mm). Peak stress and peak displacement of the mandible were mechanicaly assessed, and stress sensitivity variables were analyzed. RESULTS AND CONCLUSION:The stress and displacement of the implant were mainly concentrated in the neck of the implant. The stress of implant-bone interface mainly focused on the contact area of the implant-cortical bone interface, and the stress of the cancelous bone was relatively smal, but the stress of the cortical bone was weakened faster. When the implant length was constant, the implant diameter had a great effect on stress changes, and the stress of bone tissue was reduced with the increase of implant diameter. When the implant diameter was constant, the implant length had no significant effect on the stress of bone tissue. To sum up, the stress of bone tissue and displacement were sensitive to the change of implant diameter rather than the change of implant length. These findings indicate that implant diameter has a greater effect on stress distribution of bone tissue than the implant length, and the implants with > 1.5 mm in diameter are suitable for IV osteoid.

BACKGROUND:In the clinical orthodontics, ceramic brackets have deficiencies in the aspects of antibacterial and mechanical properties, which easily lead to the emergence of a variety of adverse events and influence the orthodontic effect. OBJECTIVE:To observe the antibacterial and mechanical properties of nano silver hydroxyapatite coating ceramic brackets. METHODS:The nano silver hydroxyapatite coating ceramic brackets were prepared. Scanning electron microscopy was used to observe the coating surface. Coating antibacterial experiment was conducted. Totaly 50 in vitro human maxilary premolars were randomly divided into two groups (n=25 per group): experimental and control groups. Premolars in the experimental group were bonded to nano silver coating hydroxyapatite ceramic brackets, and premolars in the control group were bonded to ordinary ceramic brackets. The shear strength was detected in these two groups.RESULTS AND CONCLUSION: The overall structure of nano silver hydroxyapatite coating was order, uniform and compact. Hydroxyapatite had a porous structure with a micro-nanometer aperture and there were a large number of nano-silver particles uniformly distributed. Quantitative antibacterial experiments showed that nano silver hydroxyapatite coating ceramic brackets had a strong inhibition to Escherichia coli and Staphylococcus albus, with an antibacterial rate of more than 95%. The shear strength in the experimental group was lower than that of the control group (P < 0.05). These results demonstrate that the nano silver hydroxyapatite coating ceramic brackets have good antibacterial and mechanical properties, which meet the requirement of mechanical change in the clinical orthodontics.

OBJECTIVEThis study aims to biomechanically analyze a mini-implant at different healing times before loading.

METHODSSixty-four mini-implants with (12 +/- 1) N x cm insertion torque were placed in the low jaw of eight beagle dogs. The test mini-implants remained in the low jaw for 0, 1, 3, and 8 weeks of bone healing and for an additional 10 weeks under a force of 0.98 N. The unloaded control implants were further divided into four groups (1, 3, 8, and 10 weeks). Maximum removal torque (MRT) testing was performed to evaluate the interfacial share strength of each group. Surface analysis of the removed implants was performed by scanning electric microscope (SEM).

RESULTSThe MRT for the loading implants at 0, 1, 3, and 8 weeks of healing were 4.10, 4.25, 2.42, and 4.42 N x cm, respectively. During the healing process, the removal torque values of the 3-week implants were significantly lower than those of the other healing groups (P < 0.05). The unloaded 3-week implants also had lower removal torques (P < 0.05). The implant surface of the 3-week test group showed more fibrous bone. However, the other loading implants had more lamellar-like tissue.

CONCLUSIONA stable dangerous period occurred approximately 3 weeks after mini-implant insertion. A 3-week healing is disadvantageous to the stability of the implant. Orthodontics loading occurred immediately or after 1 week as a function of the healing time. The 8-week implant appeared to have a positive effect on peri-implant bone remodeling and implant stability.

Objective To observe the effect of cervical collar on cervical hypertension. Methods 98 patients with cervical hypertension were divided into two groups. The treatment group (n=50) wore the cervical collar, and the control group accepted massage and traction. Results 52.0% of the treatment group were cured, and 92.0% improved, which were 41.7% and 75.0% in control group respectively (P<0.05). The blood pressure reduced in the treatment group after treatment, and was less than those in the control group (P<0.05). Conclusion Cervical collar is effective on cervical hypertension.

Objective This study aims to biomechanically analyze a mini-implant at different healing times before loading. Methods Sixty-four mini-implants with (12±1) N·cm insertion torque were placed in the low jaw of eight beagle dogs. The test mini-implants remained in the low jaw for 0, 1, 3, and 8 weeks of bone healing and for an additional 10 weeks under a force of 0.98 N. The unloaded control implants were further divided into four groups (1, 3, 8, and 10 weeks). Maximum removal torque (MRT) testing was performed to evaluate the interfacial share strength of each group. Surface analysis of the removed implants was performed by scanning electric microscope (SEM). Results The MRT for the loading implants at 0, 1, 3, and 8 weeks of healing were 4.10, 4.25, 2.42, and 4.42 N·cm, respectively. During the healing process, the removal torque values of the 3-week implants were significantly lower than those of the other healing groups (P<0.05). The unloaded 3-week implants also had lower removal torques (P<0.05). The implant surface of the 3-week test group showed more fibrous bone. However, the other loading implants had more lamellar-like tissue. Conclusion A stable dangerous period occurred approximately 3 weeks after mini-implant insertion. A 3-week healing is disadvantageous to the stability of the implant. Orthodontics loading occurred immediately or after 1 week as a function of the healing time. The 8-week implant appeared to have a positive effect on peri-implant bone remodeling and implant stability.