BACKGROUND:Studies have found that probiotics have a certain preventive and therapeutic effect on peri-implantitis,and there are further explorations in the mechanism against peri-implantitis.OBJECTIVE:To review the mechanism and clinical application of probiotics in the treatment of peri-implantitis.METHODS:Relevant literature was searched on PubMed,Web of Science,CNKI,and WanFang Data,using the search terms of"probiotics,peri-implantitis,flora imbalance,immunoregulation,inflammatory reaction,mechanism of action"in Chinese and English.A total of 90 articles were finally included.RESULTS AND CONCLUSION:Probiotics have the following mechanisms.They can activate the anti-inflammatory mechanism by inhibiting the secretion of inflammatory factors and promoting the production of anti-inflammatory factors.They can destroy the cell wall of pathogenic bacteria by secreting microbial complexes and bacteriocins,reduce the pH value of biofilms,improve the composition of microorganisms in microecology,induce the change of bacterial community structure,and restore the balance of microbial population around implants.They have immunomodulatory effects and can enhance the resistance of the host oral mucosa to pathogenic bacteria in the surrounding area of the implant.In addition,probiotics can produce antibacterial compounds,offset the adhesion of pathogenic microorganisms,and regulate immune function.Through the above mechanisms,probiotics have certain potential in the adjuvant treatment of peri-implantitis,which can improve the clinical parameters of peri-implantitis and affect the microbiota.Probiotic therapy provides a new treatment option,but more long-term prospective studies are needed to further verify its effect.

BACKGROUND:In previous studies,glass materials were infiltrated into 5Y-PSZ ultra-translucent zirconia by a double sintering method to prepare 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia materials that can maintain high transparency and high flexural strength.OBJECTIVE:To evaluate the in vitro biocompatibility of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia materials.METHODS:(1)Glass materials were infiltrated into 5Y-PSZ ultra-translucent zirconia by double sintering to prepare 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia.5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia(or 5Y-PSZ ultra-translucent zirconia,3Y-TZP transparent zirconia)was placed in DMEM culture medium containing 10％fetal bovine serum for 12,24 and 72 hours,and the surface area ratio of culture medium to sample was 3 mL/cm2,and the 12-,24-and 72-hour material extracts were obtained.(2)After culturing mouse fibroblast L929 for 24 hours,the original culture medium was discarded and divided into 7 groups for culture:the control group was replaced with DMEM culture medium containing 10％fetal bovine serum by volume,and the other 6 groups were replaced with 24-hour extract of 3Y-TZP transparent zirconia,24-hour extract of 5Y-PSZ ultra-translucent zirconia,24-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,72-hour extract of 3Y-TZP transparent zirconia,72-hour extract of 5Y-PSZ ultra-translucent zirconia,and 72-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia.After 1,3,and 5 days of culture,cell growth was observed under a microscope,and the cell proliferation rate was obtained by CCK-8 assay to determine cytotoxicity.(3)Human anticoagulated blood was mixed with 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,5Y-PSZ ultra-translucent zirconia,and 3Y-TZP transparent zirconia,and the hemolysis rate was detected after 0.5 hours.Human anticoagulated blood was mixed with 12-hour extract of 3Y-TZP transparent zirconia,12-hour extract of 5Y-PSZ ultra-translucent zirconia,and 12-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,and the hemolysis rate was detected after 0.5 hours.RESULTS AND CONCLUSION:(1)Under the microscope,it could be seen that the number of cells in each group increased with the extension of culture time,and the cell morphology of each experimental group was basically the same as that of the control group.The cytotoxicity grade of the 24-hour extract of 3Y-TZP transparent zirconia group on the first day of culture was grade 0,and the cytotoxicity grade of the other experimental groups at each time period was grade 1.(2)Neither the material nor the material extract caused obvious hemolytic reaction,and the hemolytic rate was less than 5％.(3)The results showed that 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia had no significant effect on the growth and proliferation of mouse fibroblasts L929,and did not cause hemolytic reaction with human blood,and had good in vitro biocompatibility.

BACKGROUND:Studies have found that probiotics have a certain preventive and therapeutic effect on peri-implantitis,and there are further explorations in the mechanism against peri-implantitis.OBJECTIVE:To review the mechanism and clinical application of probiotics in the treatment of peri-implantitis.METHODS:Relevant literature was searched on PubMed,Web of Science,CNKI,and WanFang Data,using the search terms of"probiotics,peri-implantitis,flora imbalance,immunoregulation,inflammatory reaction,mechanism of action"in Chinese and English.A total of 90 articles were finally included.RESULTS AND CONCLUSION:Probiotics have the following mechanisms.They can activate the anti-inflammatory mechanism by inhibiting the secretion of inflammatory factors and promoting the production of anti-inflammatory factors.They can destroy the cell wall of pathogenic bacteria by secreting microbial complexes and bacteriocins,reduce the pH value of biofilms,improve the composition of microorganisms in microecology,induce the change of bacterial community structure,and restore the balance of microbial population around implants.They have immunomodulatory effects and can enhance the resistance of the host oral mucosa to pathogenic bacteria in the surrounding area of the implant.In addition,probiotics can produce antibacterial compounds,offset the adhesion of pathogenic microorganisms,and regulate immune function.Through the above mechanisms,probiotics have certain potential in the adjuvant treatment of peri-implantitis,which can improve the clinical parameters of peri-implantitis and affect the microbiota.Probiotic therapy provides a new treatment option,but more long-term prospective studies are needed to further verify its effect.

BACKGROUND:In previous studies,glass materials were infiltrated into 5Y-PSZ ultra-translucent zirconia by a double sintering method to prepare 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia materials that can maintain high transparency and high flexural strength.OBJECTIVE:To evaluate the in vitro biocompatibility of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia materials.METHODS:(1)Glass materials were infiltrated into 5Y-PSZ ultra-translucent zirconia by double sintering to prepare 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia.5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia(or 5Y-PSZ ultra-translucent zirconia,3Y-TZP transparent zirconia)was placed in DMEM culture medium containing 10％fetal bovine serum for 12,24 and 72 hours,and the surface area ratio of culture medium to sample was 3 mL/cm2,and the 12-,24-and 72-hour material extracts were obtained.(2)After culturing mouse fibroblast L929 for 24 hours,the original culture medium was discarded and divided into 7 groups for culture:the control group was replaced with DMEM culture medium containing 10％fetal bovine serum by volume,and the other 6 groups were replaced with 24-hour extract of 3Y-TZP transparent zirconia,24-hour extract of 5Y-PSZ ultra-translucent zirconia,24-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,72-hour extract of 3Y-TZP transparent zirconia,72-hour extract of 5Y-PSZ ultra-translucent zirconia,and 72-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia.After 1,3,and 5 days of culture,cell growth was observed under a microscope,and the cell proliferation rate was obtained by CCK-8 assay to determine cytotoxicity.(3)Human anticoagulated blood was mixed with 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,5Y-PSZ ultra-translucent zirconia,and 3Y-TZP transparent zirconia,and the hemolysis rate was detected after 0.5 hours.Human anticoagulated blood was mixed with 12-hour extract of 3Y-TZP transparent zirconia,12-hour extract of 5Y-PSZ ultra-translucent zirconia,and 12-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,and the hemolysis rate was detected after 0.5 hours.RESULTS AND CONCLUSION:(1)Under the microscope,it could be seen that the number of cells in each group increased with the extension of culture time,and the cell morphology of each experimental group was basically the same as that of the control group.The cytotoxicity grade of the 24-hour extract of 3Y-TZP transparent zirconia group on the first day of culture was grade 0,and the cytotoxicity grade of the other experimental groups at each time period was grade 1.(2)Neither the material nor the material extract caused obvious hemolytic reaction,and the hemolytic rate was less than 5％.(3)The results showed that 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia had no significant effect on the growth and proliferation of mouse fibroblasts L929,and did not cause hemolytic reaction with human blood,and had good in vitro biocompatibility.

ObjectiveTo explore the role of cucurbitacin B （CuB） in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB（0.2， 0.4， 0.8 μmol·L^-1）on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium （MTT） assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay， and the levels of lactate dehydrogenase （LDH） in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species （ROS） levels in 4T1 cells were detected by flow cytometry， and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells， solute carrier family 7 member 11 （SCL7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， transferrin receptor protein 1 （TFR1）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with that in the blank group， the survival rate of 4T1 cells in CuB groups was significantly decreased （P<0.05）， and the number of cell clones in CuB groups was significantly reduced （P<0.01）. In addition， compared with that in the blank group， the leakage of LDH in cells in CuB groups was significantly increased （P<0.01）， and the mitochondrial membrane potential of cells in CuB groups decreased significantly （P<0.01）. Cellular ROS levels were significantly elevated in CuB groups （P<0.01）. The mitochondria of cells in CuB groups were obviously wrinkled， and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group， the protein expression of p53， ACSL4， and TFR1 were significantly up-regulated in CuB groups （P<0.05）， and that of SLC7A11， GPX4， and FTH1 were significantly down-regulated （P<0.05）. ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53， which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe³⁺ and down-regulates the expression of FTH1 to reduce the ability of iron storage， resulting in an elevated free Fe²⁺ level. It catalyzes the Fenton reaction， generates excess ROS， imbalances the antioxidant system and iron metabolism， and then induces ferroptosis in 4T1 cells.

ObjectiveTo explore the role of cucurbitacin B （CuB） in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB（0.2， 0.4， 0.8 μmol·L^-1）on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium （MTT） assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay， and the levels of lactate dehydrogenase （LDH） in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species （ROS） levels in 4T1 cells were detected by flow cytometry， and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells， solute carrier family 7 member 11 （SCL7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， transferrin receptor protein 1 （TFR1）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with that in the blank group， the survival rate of 4T1 cells in CuB groups was significantly decreased （P<0.05）， and the number of cell clones in CuB groups was significantly reduced （P<0.01）. In addition， compared with that in the blank group， the leakage of LDH in cells in CuB groups was significantly increased （P<0.01）， and the mitochondrial membrane potential of cells in CuB groups decreased significantly （P<0.01）. Cellular ROS levels were significantly elevated in CuB groups （P<0.01）. The mitochondria of cells in CuB groups were obviously wrinkled， and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group， the protein expression of p53， ACSL4， and TFR1 were significantly up-regulated in CuB groups （P<0.05）， and that of SLC7A11， GPX4， and FTH1 were significantly down-regulated （P<0.05）. ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53， which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe³⁺ and down-regulates the expression of FTH1 to reduce the ability of iron storage， resulting in an elevated free Fe²⁺ level. It catalyzes the Fenton reaction， generates excess ROS， imbalances the antioxidant system and iron metabolism， and then induces ferroptosis in 4T1 cells.

Objective To study the seasonal distribution characteristics of polycyclic aromatic hydrocarbons (PAHs) in PM_2.5 in Lianyungang City, and analyze the sources of PAHs pollution, and to evaluate the health risks of PAHs in different seasons. Methods PM2.5 samples were collected regularly from January 2019 to December 2023, and 16 types of PAHs were determined by HPLC. Kruskal-Wallis H test was used to compare the concentrations of PM2.5 and PAHs in different years and seasons. The source of PAHs was analyzed by characteristic ratio and principal component analysis (PCA). Health risks were assessed using the BaP equivalent method and the incremental lifetime cancer risk (ILCR) model. Results The annual exceedance rates of PM_2.5 and BaP in Lianyungang showed a decreasing trend from 2019 to 2023. PM_2.5, total PAHs and PAHs monomers (except Ace, Flu and Acy) all showed significant seasonal differences, with the highest concentration in winter (P<0.001). The average proportion of 4-ring PAHs was the highest and the average proportion of 2-ring PAHs was the lowest. The proportion of 5-6 ring PAHs was relatively high in winter and spring. PM2.5and PAHs were negatively correlated with temperature, relative humidity and precipitation, and were positively correlated with atmospheric pressure. PM_2.5 was negatively correlated with wind speed, while some PAHs monomers were positively correlated with wind speed. The characteristic ratio and PCA results showed that the main sources of PAHs in Lianyungang City were mixed sources of road dust and vehicle emissions, oil pollution sources and biomass combustion sources. The results of ILCR showed that the highest risk was found in adults, with males slightly higher than females. In Lianyungang, the maximum value of ILCR in winter was more than 10-6 in people over 9 years old. Conclusion The main sources of PAHs in PM_2.5 in Lianyungang City are mixed sources of road dust and vehicle emissions, oil pollution sources, and biomass combustion sources. Under the current exposure level of PAHs in PM_2.5, residents have a certain potential carcinogenic risk.

Through consulting herbal medicine， medical books， and local chronicles from past dynasties to modern times， this paper systematically researched Spatholobi Caulis from name， origin， producing areas， harvesting， processing， usage， quality evaluation， functions and indications， providing a reference for the development and utilization of famous classical formulas containing Spatholobi Caulis. According to the research， Spatholobi Caulis was first recorded in the Annals of Shunning Prefecture from the Qing dynasty. It was originally a medicinal herb commonly used in Shunning， Yunnan， and was named from the red juice resembling chicken blood that flowed out after the vein was cut off. The mainstream original plants of each dynasty were Kadsura heteroclita and Spatholobus suberectus. Among them， K. heteroclita mainly focused on dispersing blood stasis and unblocking meridians， mainly treating rheumatic pain and injuries caused by falls or blows， and it is mostly used as the raw material of Jixueteng ointments. S. suberectus was commonly used as decoction pieces in decoction， which had the functions of promoting blood circulation and replenishing blood， activating meridians and collaterals， and mainly used for treating anemia， irregular menstruation， and rheumatic bone pain. The production area of Spatholobi Caulis recorded in the Qing dynasty was Yunnan. Currently， the main production area of S. suberectus is Guangxi， while the main production area of K. interior is Yunnan. In the Qing dynasty， the usage of Spatholobi Caulis was an individual prescription with other herbs before making ointments， which was usually composed of the juice of it， safflower， angelica， and glutinous rice. But in modern times， Spatholobi Caulis is mostly sliced and dried for use. The quality of Spatholobi Caulis is often determined by the number of reddish-brown concentric circles on the cut surface， with a higher number indicating better quality. Additionally， the presence of resinous secretions is also considered desirable. Based on the research findings， it is suggested that when developing famous classical formulas containing Spatholobi Caulis， the choice of the primary source should be S. suberectus or K. heteroclita， taking into consideration the therapeutic effects of the formula. It is also recommended that the latest plant classification be referenced in the next edition of Chinese Pharmacopoeia， adjusting the primary source of Kadsurae Caulis to K. heteroclita to avoid confusion caused by inconsistent original names， and the functions adjust to promote Qi circulation and relieve pain， disperse blood stasis and unblock collaterals， treating injuries caused by falls and bruises.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95％of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.

OBJECTIVE: To investigate the clinical phenotype and genotype features of children with Epileptic encephalopathy caused by PCDH19 mutations. METHODS: Four children with epilepsy caused by PCDH19 gene mutations who were treated at Shanghai Children's Medical Center from August 2015 to May 2024 were selected as study subjects. A retrospective study method was used to collect the clinical data of the patients. Peripheral venous blood samples (2 mL each) were collected from the patients and their parents. Genomic DNA was extracted, and whole exome sequencing (WES) was performed, followed by family verification of candidate variants by Sanger sequencing. Pathogenicity of the candidate variants was classified according to the "Genetic Variation Classification Standards and Guidelines" established by the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Shanghai Children's Medical Center (Approval No. SCMCIRB-K2020060-1). RESULTS: The patients comprised of 3 females and 1 male, all presenting symptoms before the age of 3. Patients 1-3 exhibited generalized tonic-clonic seizures, while patient 4 manifested focal seizures accompanied by impaired consciousness. In addition to epilepsy, patient 2 showed language delay and patient 3 had frequent panic attacks. WES results identified four pathogenic PCDH19 variants these patients, including 2 previously unreported frameshifting mutations,1 hotspot missense mutation, and 1 mosaic missense mutation with a 32.4% mutation rate. The pathogenic mutation in patient 2 was inherited from her father, while the remaining 3 patients had de novo pathogenic mutations. CONCLUSION Children with PCDH19 gene mutations may exhibit early-onset refractory epilepsy, cognitive impairment, and developmental delay. Females are predominantly affected by the PCDH19 mutations, although males with mosaic mutations can also be affected. The genetic and clinical heterogeneity observed among patients 1-4 indicated the diverse nature of epilepsy related to the PCDH19 gene mutations. PCDH19 gene mutations may be the genetic cause of epilepsy in these affected children, which also enriched the mutational spectrum of the PCDH19 gene.
Child, Preschool ; Female ; Humans ; Infant ; Male ; Cadherins/genetics* ; Epilepsy/genetics* ; Exome Sequencing ; Mutation ; Phenotype ; Protocadherins ; Retrospective Studies