Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Organoids,recognized as invaluable models in tumor and stem cell research,assume a pivotal role in the meticulous analysis of diverse datasets pertaining to their growth dynamics,drug screening processes and related phenomena.However,the manual scrutiny and conventional statistical methodologies employed in handling organoid data often grapple with challenges such as diminished precision and efficiency,heightened complexity,escalated human resource requirements,and a degree of subjectivity.Acknowledging the remarkable efficacy of artificial intelligence(AI)in the realms of biology and medicine,the incorporation of AI into organoid research stands poised to enhance the objectivity,precision and expediency of analyses.This integration empowers organoids to more effectively fulfill objectives such as disease modeling,drug screening and precision medicine.Notably,significant strides have been made in AI-driven analyses of organoid image data.The amalgamation of deep learning into image analysis facilitates a more meticulous delineation of the microstructural intricacies and nuanced changes within organoids,achieving a level of accuracy akin to that of experts.This not only elevates the precision of organoid morphology and growth recognition,but also contributes to substantial time and cost savings in research endeavors.Furthermore,the infusion of AI technology has yielded breakthroughs in the processing of organoid omics data,resulting in heightened efficiency in data processing and the identification of latent gene expression patterns.This furnishes novel tools for comprehending cellular development and unraveling the intricate mechanisms underlying various diseases.In addition to image data,AI techniques applied to diverse organoid datasets,encompassing electrical signals and spectra,have realized an unbiased classification of organoid types and states,embarking on a comprehensive journey towards characterizing organoids holistically.In the pivotal domain of drug screening for organoids,AI emerges as a stalwart companion,providing robust support for real-time process monitoring and result prediction.Leveraging high-content microscopy images and sophisticated deep learning models,researchers can dynamically monitor organoid responses to drugs,effecting non-invasive detection of drug impacts and amplifying the precision and efficiency of drug screening processes.Despite the significant strides made by AI in organoid research,challenges persist,encompassing hurdles in data acquisition,constraints in sample quality and quantity,and quandaries associated with model interpretability.Overcoming these challenges necessitates dedicated future research efforts aimed at enhancing data consistency,fortifying model interpretability,and exploring methodologies for the seamless fusion of multimodal data.Such endeavors are poised to usher in a more comprehensive and dependable application of AI in organoid research.In summation,the integration of AI technology introduces unparalleled opportunities to organoid research,resulting in noteworthy advancements.Nevertheless,interdisciplinary research and collaborative efforts remain imperative to navigate challenges and propel the more profound integration of AI into organoid research.The future holds promise for AI to assume an even more prominent role in advancing organoid research toward clinical translation and precision medicine.

Colorectal cancer （CRC） is a malignant tumor of the intestinal tract with changes in bowel habits， blood in the stool， and pain as the main clinical manifestations. With the change in lifestyle and diet structure in recent years， the incidence of CRC has been increasing year by year. The pathogenesis of CRC is closely related to abnormal immune response and chronic inflammation， intestinal microbial dysbiosis， and the production of oncogenic metabolites. There is a two-way communication between the intestinal microbiota and the body's immunity， which not only plays a key role in maintaining the body's health but also has a close relationship with the development of diseases. An increasing number of studies have shown that abnormal immune responses accelerate the disease process by producing inflammatory factors， causing chronic inflammation in the body， disrupting the intestinal mucosal barrier， and increasing mucosal permeability， thus resulting in dysbiosis of the intestinal microbial ecology and a large number of pathogenic microorganisms and their metabolites. In addition， dysbiosis of intestinal microbes， by suppressing the normal immune response， leads to the disruption of multiple metabolic pathways in the body， affecting the internal and external stress response of the intestine， inducing inflammation， and thus producing disease. Therefore， the complex crosstalk mechanism between the immune response and intestinal microbial axis is closely related to the development of CRC. Based on traditional Chinese medicine theory and clinical research， it was found that dietary factors are an important causative factor in the development of CRC. The deficiency of positive energy is the root cause of the disease， and damp-heat accumulation is the key pathogenesis. Through modern medical and biological research， it is believed that abnormal immune response is the microscopic manifestation of damp-heat entrapment， while intestinal microbial dysbiosis is the biological basis of toxic injection into the large intestine， and in the pathogenesis of CRC， the imbalance of immune response-intestinal microbial axis is compatible with damp-heat accumulation in traditional Chinese medicine. This study aims to explore the biological connotation of CRC due to damp-heat accumulation from the immune response-intestinal microbial axis， so as to interpret the pathogenesis of CRC due to damp-heat accumulation with objective data and provide new ideas and theoretical basis for the pathogenesis and treatment strategies of CRC due to damp-heat accumulation.

OBJECTIVE To explore the potential mechanism of the effect of Xuebijing injection （XBJ） on neurological function and survival of rats after cardiac arrest （CA）/cardiopulmonary resuscitation （CPR） based on the S-nitrosoglutathione reductase （GSNOR）/S-nitrosoglutathione （GSNO） pathway. METHODS The CA/CPR rat model was established by ventricular fibrillation. Using a sham operation group as control， high-throughput sequencing was employed to analyze and mine the differentially expressed genes （DEGs）. Enzyme-linked immunosorbent assay was used to determine the contents of GSNOR and GSNO in the hippocampus； the active components of XBJ were screened and subjected to molecular docking analysis with GSNOR. The rats successfully modeled using the same method were divided into model group （n＝30）， inhibitor （GSNOR inhibitor） group （n＝30）， XBJ group （n＝30） and XBJ+inhibitor group （n＝30）， and a sham operation group （n＝30） was set up. Neurological function was evaluated and survival status was recorded at 3 hours， 24 hours and 3 days after the first 89） drug intervention. The contents of GSNOR and GSNO in the hippocampus of rats were determined in each group at the 0191） above time points， and the relationship of the contents of GSNOR and GSNO with modified neurologic severity scale （mNSS） score was analyzed. RESULTS GSNOR coding gene was differentially expressed between the model group and the sham operation group. Compared with the sham operation group， GSNOR content increased significantly in the hippocampus of rats in model group， while GSNO content decreased significantly （P＜0.05）. The active components of XBJ， such as 4- methylenemiltirone and salviolone， could be bound to GSNOR protein， with the binding energy lower than －6 kcal/mol， mainly connected by hydrogen bonds. Animal experiments revealed that mNSS score and GSNOR levels in the hippocampus of rats in the model group were significantly higher than those in the sham operation group （P＜0.05）， while GSNO levels and survival rate were significantly lower than those in the sham operation group （P＜0.05）. The above indexes of rats were improved significantly in administration groups， the mNSS score in the XBJ group was significantly lower than that in the inhibitor group， the content changes of GSNOR and GSNO in the inhibitor group were more obvious than those in the XBJ group， and the various indicators in the XBJ+inhibitor group were significantly better than the XBJ group and the inhibitor group （P＜0.05）. GSNOR content was positively correlated with the mNSS score， and GSNO content was negatively correlated with the mNSS score （P＜0.05）. CONCLUSIONS XBJ can improve the neurological function of rats and enhance their survival rates after CA/CPR， the mechanism of which may be associated with the down-regulation of GSNOR and the up-regulation of GSNO.

BACKGROUND:Mesenchymal stem cells are susceptible to senescence during in vitro expansion,which greatly hinders their application in vivo and in vitro.How to improve the replicative senescence of mesenchymal stem cells is an urgent problem to be solved in tissue engineering. OBJECTIVE:To determine whether vascular endothelial growth factor combined with basic fibroblast growth factor can improve the aging of bone marrow mesenchymal stem cells caused by replicative passage. METHODS:Rat bone marrow mesenchymal stem cells were extracted by whole bone marrow adhesion method.Passage 2 cells were selected as normal control group.Passage 7 and later algebraic cells were selected as aging model group.Vascular endothelial growth factor(50 μg/L),basic fibroblast growth factor(10 μg/L),and their combination were administered.Cell proliferation was detected by CCK-8 assay.Cell senescence was observed by β-galactosidase activity staining.Cytoskeleton size and colony formation ability were observed by phalloidine staining and Giemsa staining,respectively,and the levels of senescence-related genes P16,P21,and P53 were detected by qRT-PCR.Gene expression levels of P16,P21,and P53 were tested by qRT-PCR. RESULTS AND CONCLUSION:(1)Vascular endothelial growth factor combined with basic fibroblast growth factor could promote the proliferation of aged bone marrow mesenchymal stem cells,which began to enter the plateau stage on day 9,and the absorbance value of the combined intervention group was significantly higher than that of the model group on day 9(P<0.05).(2)The phenotypic markers of the cells in the combined intervention group did not change,and the cell morphology changed from broad to slender.(3)Compared with the model group,the positive rate of β-galactosidase was significantly decreased(P<0.01);the number of nuclei increased(P<0.001);the total area of cytoskeleton increased(P<0.01);colony formation ability was enhanced(P<0.05);expression level of P16 was decreased(P<0.01)in the combined intervention group.These results indicate that vascular endothelial growth factor combined with basic fibroblast growth factor can improve the senescence of bone marrow mesenchymal stem cells caused by replicative passage without changing the cell phenotype.

OBJECTIVE To study the pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog. METHODS The plasma concentration of esketamine hydrochloride in rats was determined by LC-MS/ MS after intravenous injection of esketamine hydrochloride solution and nasal administration of esketamine hydrochloride； the pharmacokinetic parameters were calculated by using Phoenix WinNonlin 8.1.0 software. Using the maxillary mucosa of isolated bullfrog as a model， the morphological changes of maxillary mucosa were investigated， and the duration and recovery of ciliary oscillation were recorded after nasal administration of esketamine hydrochloride. RESULTS The peak of blood concentration occurred 2 min after nasal administration of esketamine hydrochloride； cmax was （814.58±418.80） ng/mL， AUC0－∞ was （203.75± 92.76） ng·h/mL， and the absolute bioavailability was 60.68%. After nasal administration of esketamine hydrochloride， it was observed that the cilia of bullfrog were arranged neatly， the edges were clear， the cilia tissue structure was complete and the cilia moved actively. The cilia movement time was （178.17±13.30） min for the first time， and after the cilia moved again， the ciliary movement time measured again was （24.50±9.19）min with a relative movement percentage of 53.56%. CONCLUSIONS Esketamine hydrochloride nasal spray has a rapid onset of action， high bioavailability， and low ciliary toxicity.

Most of the current research on depression focuses on neuronal regulation,while the astrocytic mechanism of depression is far from explored.Astrocytes are the most numerous and widely distributed glial cells in the central nervous system.With a complex structural morphology,astrocytes play an important role in a variety of neuropsychiatric disorders by interacting with neuronal synapses,vasculature and other glial cells.Recent studies have shown that astrocytes may be involved in depression by regulating monoamine transmitters,glutamate cycle,synaptic plasticity,energy metabo-lism,and neuroinflammation.This review is intended to inspire new ideas for the treatment of depres-sion and the development of novel drugs based on astrocyte regulation.

Objective:To construct a safe operation management path based on work chain and extension matter-element model,and to explore its application effect in clinical management of magnetic resonance imaging(MRI)equipment.Methods:The safety risk evaluation indicators was developed from the perspective of MRI equipment work chain at the levels of personnel,equipment,environment and system.The rating of safety characteristic indicators of equipment was carried out and risk control management strategy was formulated by adopting extensible matter element model.The MRI equipment in clinical use in the Imaging Department of Shucheng People's Hospital from January 2019 to December 2021 was selected,and the standard process management mode(referred to as standard process mode)and risk assessment control mode(referred to as risk control mode)were adopted respectively for equipment operation management.The safety risk event control rate,safety operation management standardization and professional capability of staff of MRI equipment under two different management modes were compared.Results:Among 62 safety risk events of MRI equipment managed by risk control mode,the control rates of extremely dangerous,highly dangerous and significant dangerous events were 1.61%(1/62),4.84%(3/62)and 8.06%(5/62),respectively,which were lower than those of the standard process mode,the difference was statistically significant(x2=5.613,4.567,9.241,P<0.05).Among 480 cases of safety operation inspection carried out by risk control mode management,the standardization of patient reception,equipment use,operating environment and management system were 96.25%(462/480),98.96%(475/480),99.17%(476/480)and 97.50%(468/480),respectively,which were higher than those of the standard process mode,the difference was statistically significant(x2=18.631,17.563,7.353,8.789,P<0.05).The annual assessment scores of MRI technicians,nurses and medical engineering engineers of the imaging department adopting risk control mode were(91.87±4.56)points,(94.54±3.27)points and(91.45±4.95)points,respectively,which were higher than those of the standard process mode,the difference was statistically significant(t=3.291,4.277,4.292,P<0.05).Conclusion:The risk control management mode based on work chain and extension matter-element model can comprehensively explore the factors affecting the safe operation of MRI equipment,effectively control the incidence of high-risk events,improve the quality of clinical operation and operation management of MRI equipment.

Objective:To investigate the feasibility of expectant management of different degrees of vaginal fluid in pregnant women with premature rupture of membranes in the second trimester.Methods:A retrospective cohort study was conducted to collect 103 pregnant women who were diagnosed with premature rupture of membranes in the second trimester of pregnancy and insisted on continuing the pregnancy in Shanxi Bethune Hospital from July 2012 to July 2022. According to the degree of vaginal fluid, pregnant women were divided into rupture group (with typical vaginal fluid, 48 cases) and leakage group (without typical vaginal fluid, 55 cases). The rupture latency (the time from rupture of membranes to termination of pregnancy), gestational weeks of termination, indications and methods of termination of pregnancy, maternal infection related indicators and perinatal outcomes were compared between the two groups. Univariate regression model was used to analyze the correlation between different degrees of vaginal fluid in pregnant women with premature rupture of membranes and maternal and neonatal outcomes.Results:(1) Obstetric indicators: there was no significant difference in the gestational age of rupture of membranes between the two groups ( P>0.05). However, the proportion of rupture latency >28 days in the leakage group was significantly higher than that in the rupture group [42% (23/55) vs 13% (6/48); χ2=33.673, P<0.001], and the incidence of pregnancy termination ≥28 weeks was significantly higher [47% (26/55) vs 19% (9/48); χ2=9.295, P=0.002]. (2) Indications and methods of termination: the incidence of progressive reduction of amniotic fluid as the indication for termination in the leakage group was significantly lower than that in the rupture group [22% (12/55) vs 42% (20/48); χ2=4.715, P=0.030], and the incidence of full-term termination in the leakage group was significantly higher than that in the rupture group [31% (17/55) vs 12% (6/48); χ2=5.008, P=0.025], while there were no significant differences in the indications of termination of pregnancy, including amniotic cavity infection, uterine contraction failure and fetal distress between the two groups (all P>0.05). The incidence of induced labor or spontaneous contraction in the leakage group was significantly lower than that in the rupture group [53% (29/55) vs 81% (39/48); χ2=9.295, P=0.002], while the cesarean section rate and vaginal delivery rate were similar between the two groups (both P>0.05). (3) Infection related indicators: the incidence of amniotic cavity infection in the leakage group was significantly higher than that in the rupture group [31% (17/55) vs 13% (6/48); χ2=4.003, P=0.045]. However, there were no significant differences in the elevation of inflammatory indicators, the positive rate of cervical secretion bacterial culture and the incidence of tissue chorioamnionitis between the two groups (all P>0.05). (4) Perinatal outcomes: the live birth rate in the leakage group was significantly higher than that in the rupture group [51% (28/55) vs 27% (13/48); χ2=5.119, P=0.024]. The proportion of live births with 1-minute Apgar score >7 in the leakage group was significantly higher than that in the rupture group [38% (21/55) vs 17% (8/48); χ2=4.850, P=0.028]. However, there were no significant differences in the birth weight of live births and the incidence of neonatal complications between the two groups (all P>0.05). (5) Univariate regression analysis showed that compared with the rupture group, the leakage group had a higher risk of pregnancy termination at ≥28 gestational weeks ( RR=2.521, 95% CI: 1.314-4.838; P=0.002), amniotic infection ( RR=2.473, 95% CI: 1.061-5.764; P=0.025), perinatal survival ( RR=1.880, 95% CI: 1.104-3.199; P=0.014). Conclusion:Compared with pregnant women with typical vaginal fluid in the second trimester of premature rupture of membranes, expectant treatment for pregnant women with atypical vaginal fluid is more feasible, which could effectively prolong the gestational weeks and improve the perinatal live birth rate.

OBJECTIVE To explore the applicablity of 'BlueScreen HC'(BSHC),a high throughput genotoxicity screening system based on human growth arrest and DNA damage inducible 45α(GADD45α)gene,in detecting the genotoxicity of migrants mixtures from food contact materials(FCM).METHODS The 2000 bp sequence upstream of the open reading frame of human GADD45α gene was used as the promoter to construct the lentiviral plasmid pEZX-LvPG04,which was double labeled by purinamycin and Gausluciferase(Gluc),and the lentiviral plasmid was infected with human lymphoblastocyte TK6 to obtain a stable transmutation cell line TK6-Gluc.Methyl methylate(MMS)at concentrations of 0,1.56,3.13,6.25,12.5,25.0 and 50.0 mg·L-1 was selected as the genotoxin without liver S9,cyclophosphamide(CTX)0,0.78,1.56,3.13,6.25,12.5,25.0 mg·L-1 was selected as the pre-genotoxin with liver S9,and dimethyl sulfoxide(DMSO)0,0.35,0.69,1.38,2.75,5.5 and 11.0 g·L-1 was selected as the non-genotoxin.The constructed BSHC was verified with the above known genetic positive and negative substance respectively.Polybutyleneadipate-co-terephthalate(MS/PBAT)was tested using 4% (V/V)acetic acid,and 10%,20%,50% and 95% (V/V)ethanol as food simulants at 40℃for 24 hours to obtain 5 multi-component migrants of MS/PBAT that were obtained by using DMSO as a solvent.TK6-Gluc cells were treated with 5 multi-component migrants of MS/PBAT at concentrations of 0,0.38,0.76,1.53,3.05,6.10 and 12.20 g·L-1 with or without liver S9.Cells were treated without liver S9 for 48 h.Cells treated with liver S9-mix were incubated for 3 h at a final concen-tration of 1% (V/V)liver S9 before being washed and re-suspended in fresh recovery media for another 45 h.After exposure,the cell viability was detected using the CCK-8 cell activity kit,and the Gluc Lumi-nescence in the medium was detected with Secrete-PairTM Gaussia Luciferase Assay Kit.In addition,the mutagenicity on Salmonella typhimurium TA98 and TA100 was detected by micro-fluctuation Ames test with 5 multi-component migrants of MS/PBAT at concentrations of 3.05 and 12.20 g·L-1.The in vitro mammalian cell chromosome aberration test was performed on CHL cells with 5 multi-component migrants of MS/PBAT at concentrations of 3.05 and 12.20 g·L-1 to detect the chromosomal aberration.The results of genotoxicity were compared with those of BSHC.RESULTS The lowest effect centra-tion(LEC;<80% relative cell viability)and the coytotoxicity(<30% relative cell viability)was defined.A positive genotoxicity result threshold was determined at 1.8-fold relative induction.For the liver S9 protocol,the same process was followed,and the decision threshold derived was 1.5-fold relative Gluc induction.It is considered as genetic substance only when a positive genotoxicity result was reached and there was no cytotoxicity.Compared with the vehicle control group,no genotoxicity was observed at all concentration of DMSO by BSHC.MMS 12.5,25.0 and 50.0 mg·L-1 produced genotoxicity without liver S9 while CTX 6.25,12.5 and 25.0 mg·L-1 produced genotoxicity with liver S9.Significant cell growth inhibition was observed in 95% ethanol migrants of MS/PBAT at concentrations of 6.10 and 12.20 g·L-1,and in 50% ethanol migrants of MS/PBAT at a concentration of 12.20 g·L-1 without liver S9.No cytotoxicity with a relative cell viability below 30% was observed in any of the treatment groups,and no high expression of Gluc was observed.Therefore,none of the 5 multi-component migrants produced genotoxicity without liver S9.Significant cell growth inhibition was observed in 95% ethanol migrants of MS/PBAT at a concentration of 12.20 g·L-1,and in 4% acetic acid migrants of MS/PBAT at concentrations of 6.10 and 12.20 g·L-1 with liver S9.No cytotoxicity with a relative cell viability below 30% was observed in any of the treatment groups.No high expression of Gluc was observed.There-fore,none of the 5 multi-component migrants produced genotoxicity with liver S9.In the micro fluctua-tion Ames test,when 5 multi-component migrants of MS/PBAT were treated with concentrations of 3.05 and 12.20 g·L-1 on TA98 and TA100 strains,there was no significant difference in the number of muta-genic positive wells compared with DMSO control group with or without liver S9,indicating that no mutagenic effect was produced.When CHL cells were treated with 5 multi-component migrants of MS/PBAT at concentration of 3.05 and 12.20 g·L-1,compared with DMSO control group,there was no signifi-cant difference in chromosome aberration rate of CHL cells with or without liver S9.CONCLUSION BSHC based on GADD45α gene has been established,which can be used for in vitro genotoxicity eval-uation of migrants mixtures of FCM,but further exploration of its minimum effective concentrations is still needed,and more types of mixtures need to be applied for further validation.