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

Objective To investigate necroptosis-related diagnostic biomarkers of bronchopulmo-nary dysplasia(BPD)and their relationships with the immune microenvironment through the analysis of necroptosis-related genes(NRGs)in BPD.Methods The dataset GSE32472 was downloaded from the Gene Expression Omnibus(GEO)database,and NRGs were obtained from the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway and Gene Cards databases.Differentially expressed necroptosis-related genes(DE-NRGs)were screened,and their biological functions and pathways were explored through functional enrichment analysis.Machine learning algorithms,inclu-ding least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE),were applied to screen feature genes.The Cell-type Ⅰdentification By Estimating Relative Subsets of RNA Transcripts(CIBERSORT)algorithm and the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues using Expression Data(ESTIMATE)algo-rithm were used to explore the immune infiltration characteristics of BPD.Spearman correlation anal-ysis between feature genes and immune cells was performed using the"corrplot"package in R lan-guage.Results A total of 19 DE-NRGs were identified.The main biological functions and path-ways of DE-NRGs included the regulation of necroptosis and inflammatory responses.Three feature genes,namely flotillin-2(FLOT2),CASP8 and FADD-like apoptosis regulators(CFLAR),and charged multivesicular body protein 7(CHMP7),were further screened to construct a nomogram.In the validation sets GSE8586 and GSE188944,the area under the curve(AUC)values were all greater than 0.7.CIBERSORT analysis revealed that BPD group presented a higher proportion of naive B cells,neutrophils,eosinophils and resting mast cells compared to control group(P＜0.05).Meanwhile,the proportion of CD8+T cells,CD4+naive T cells,CD4+resting memory T cells,regulatory T cells,resting natural killer(NK)cells,M0 macrophages,M2 macrophages and activated dendritic cells was lower than that in the control group(P＜0.05).ESTIMATE analysis showed that the stromal score in the BPD group was higher than that in the control group,while the immune score was lower,with statistically significant differences(P＜0.05).Correlation analysis between the three feature genes and ESTIMATE scores indicated that FLOT2 and CFLAR were posi-tively correlated with the stromal score and negatively correlated with the immune score,whereas CHMP7 was positively correlated with the immune score and negatively correlated with the stromal score.Conclusion The three necroptosis-related feature genes can serve as diagnostic biomarkers for BPD-related necroptosis,with high diagnostic efficacy.They may play an important roles through immune mechanisms,providing new insights and theoretical references for the early diagnosis and immune intervention of BPD.

Objective To explore the effect of cancer related anemia on the abundance of SARS-CoV-2 specific memory CD8+T cells in peripheral blood.Methods A total of 34 HLA-A*11∶01 positive patients with middle-and late-stage tumors admitted in the Rocket Force Medical Center of PLA from June to July 2023 were enrolled in this study.According to hemoglobin(HGB)level,they were divided into non anemia group(≥120 g/L,n=14),mild anemia group(90～120 g/L,n=14),and moderate to severe anemia group(＜90 g/L,n=6).After their peripheral blood mononuclear cells were isolated,memory CD8+T cells were stimulated by the epitopes of SARS-CoV-2 and then expanded.Positive epitopes were screened using enzyme-linked immunosorbent spot(ELISP OT)assay,and then MHC-peptide Tetramers were constructed.The proportion and number of Tetramer+cells and the number of ELISPOT spots were detected in the expanded cells to reflect the abundance of SARS-CoV-2 specific memory CD8+T cells.The relevance of patients'HGB level with the proportion and number of Tetramer+cells and the number of ELISPOT spots was analyzed.The differences of the proportion and number of Tetramer+cells and the number of ELISPOT spots was analyzed in different groups.Results Among the 34 patients,there were 25 males and 9 females,at an age range of 36～78(median 57)years.The proportion and number of Tetramer+cells and the number of ELISPOT spots were positively correlated with HGB level(P＜0.05).The proportion and number of Tetramer+cells and the number of ELISPOT spots were significantly decreased in patients with moderate to severe anemia than the non anemia patients(P＜0.05).Conclusion The abundance of SARS-CoV-2 specific memory CD8+T cells in peripheral blood is positively correlated with patients'HGB level,indicating that CRA may increase the susceptibility of patients to viruses by reducing the abundance of memory CD8+T cells in peripheral blood.

Objective:To explore the clinical characteristics of interleukin-6 (IL-6) and interleukin-8 (IL-8) in cerebrospinal fluid (CSF) of children with bacterial meningitis (BM) and provide reference for clinical diagnosis and treatment of BM.Methods:The clinical data of BM children hospitalized in Women and Children′s Medical Center Affiliated to Guangzhou Medical University from December 2019 to March 2022 were collected and retrospectively analyzed in this case series study.Cytokines in CSF of these children were detected at least twice during the treatment. t test, Mann-Whitney test or analysis of variance were carried out for statistical analysis. Results:There were 40 patients included in this study.The age of onset was 2(1, 8) months, ranging from 2 days to 8 years, and the length of time from onset to hospitalization was (15±17) days, ranging from 1 day to 69 days.The main symptoms at the onset were fever (40 cases, 100%), poor mental state (16 cases, 35.0%), convulsion (9 cases, 22.5%), and vomiting (9 cases, 22.5%).According to pathogens, the patients were divided into the Streptococcus agalactia group (GBS group, 9 cases), Streptococcus pneumoniae group (SP group, 9 cases), other bacteria group (9 cases), and unknown bacteria group (13 cases).The levels of cytokines in the CSF of BM children were increased, along with significantly elevated levels of IL-6 and IL-8 within 1 st week of BM, followed by the peak at 2 nd-3 rd weeks, and then levels of IL-6 and IL-8 presented an overall decreasing trend with the progression of BM.The level of IL-6 in CSF of 10 cases significantly decreased in the 4 th week of BM [within 2 weeks: 773.5(164.1, 1 781.2) ng/L vs. 4 th week: 10.8(2.2, 21.1) ng/L, P=0.005].Such statistical differences didn′t occur to the level of IL-8 [within 2 weeks 182.9(33.6, 657.7) ng/L vs. 4 th week: 92.9(22.6, 226.6) ng/L, P=0.303].After effective antibiotic therapy, 6 patients had elevated white blood cell count in CSF during the 4 th-20 th weeks, with or without repeating intermittent fever.Among them, 4 cases of GBS and 1 case of SP were negative for pathogens in CSF during the retest after treatment, and the levels of IL-6 and IL-8 [(149.1-4 218.6) ng/L and (124.2-1 890.3) ng/L, respectively] in CSF were elevated.Low-dose glucocorticoid was administered for anti-inflammatory treatment, with additional gamma globulin for 1 case and Ibuprofen instead for 1 case.Subsequently, the fever completely subsided.The white blood cell count in CSF decreased significantly ( P=0.024). Conclusions:The levels of IL-6 and IL-8 in CSF increase significantly in the acute phase of BM and generally decrease with the progression of BM.If they are still significantly elevated in the later course of BM, it should be noted that an intracranial hyperinflammatory response may occur, especially when the pathogenic bacteria are GBS or SP.

Objectives:To explore the antitumor effects of redox-responsive nanoparticles containing platinum(Ⅳ)—NP@Pt(Ⅳ) in ovarian cancer.Methods:Redox-responsive polymer carriers were synthesized. Polymer carriers and platinum(Ⅳ)—Pt(Ⅳ) can self-assemble into NP@Pt(Ⅳ). Inductively coupled plasma mass spectrometry was performed to detect the platinum release from NP@Pt(Ⅳ) in reducing environment and the platinum content in ovarian cancer cells ES2 treated with cisplatin, Pt(Ⅳ) and NP@Pt(Ⅳ). The proliferation ability of the ovarian cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was assessed by flow cytometry. Collection of primary ovarian cancer tissues from patients with primary high-grade serous ovarian cancer who were surgically treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from October to December 2022. The high-grade serous ovarian cancer patient-derived xenograft (PDX) mice were intravenously injected with Cy7.5 labeled NP@Pt(Ⅳ) followed by in vivo imaging system. Mice were treated with PBS, cisplatin and NP@Pt(Ⅳ). Tumor volume and weight were measured in each group. Necrosis, apoptosis and cell proliferation of tumor tissues were detected by hematoxylin-eosin (HE) staining, TUNEL fluorescence staining and Ki-67 immunohistochemistry staining. Body weight and HE staining of heart, liver, spleen, lung and kidney of mice in each group were measured.Results:The platinum release of NP@Pt(Ⅳ) after 48 hours in reducing environment was 76.29%, which was significantly higher than that of 26.82% in non-reducing environment ( P<0.001). The platinum content in ES2 cells after 4 hours and 7 hours of treatment with NP@Pt(Ⅳ) (308.59, 553.15 ng/million cells) were significantly higher than those of Pt(Ⅳ) (100.21, 180.31 ng/million cells) and cisplatin (43.36, 50.36 ng/million cells, P＜0.05). The half inhibitory concentrations of NP@Pt(Ⅳ) in ovarian cancer cells ES2, A2780, A2780DDP were 1.39, 1.42 and 4.62 μmol/L, respectively, which were lower than those of Pt(IV) (2.89, 7.27, and 16.74 μmol/L) and cisplatin (5.21, 11.85, and 71.98 μmol/L). The apoptosis rate of ES2 cells treated with NP@Pt(Ⅳ) was (33.91±3.80)%, which was significantly higher than that of Pt(Ⅳ) [(16.28±2.41)%] and cisplatin [(15.01±1.17)%, P＜0.05]. In high-grade serous ovarian cancer PDX model, targeted accumulation of Cy7.5 labeled NP@Pt(Ⅳ) at tumor tissue could be observed. After the treatment, the tumor volume of mice in NP@Pt(IV) group was (130±98) mm 3, which was significantly lower than those in control group [(1 349±161) mm 3, P<0.001] and cisplatin group [(715±293) mm 3, P=0.026]. The tumor weight of mice in NP@Pt(IV) group was (0.17±0.09)g, which was significantly lower than those in control group [(1.55±0.11)g, P<0.001] and cisplatin group [(0.82±0.38)g, P=0.029]. The areas of tumor necrosis and apoptosis in mice treated with NP@Pt(Ⅳ) were higher than those in mice treated with cisplatin. Immunohistochemical staining revealed that there were low expressions of Ki-67 at tumor tissues of mice treated with NP@Pt(Ⅳ) compared with cisplatin. The change in body weight of mice in NP@Pt(Ⅳ) group was not significantly different from that of the control group [(18.56±2.04)g vs.(20.87±0.79)g, P=0.063]. Moreover, the major organs of the heart, liver, spleen, lung, and kidney were also normal by HE staining. Conclusion:Redox-responsive NP@Pt(Ⅳ), produced in this study can enhance the accumulation of cisplatin in ovarian cancer cells and improve the efficacy of ovarian cancer chemotherapy.

OBJECTIVE: To explore the genetic basis for a child with myopathy and cerebellar atrophy with ataxia. METHODS: Clinical examinations and laboratory testing were carried out for the patient. The proband and the parents' genomic DNA was extracted from peripheral blood samples and subjected to trio whole-exome sequencing. Candidate variant was validated by Sanger sequencing. RESULTS: The 1-year-and-8-month-old boy manifested motor developmental delay, ataxia, hypomyotonia, increased serum creatine kinase. Cranial MRI showed cerebellar atrophy with progressive aggravation. Genetic testing revealed that the patient has harbored compound heterozygous variants of the MSTO1 gene, namely c.13delG (p.Ala5ProfsTer68) and c.971C>T (p.Thr324Ile), which were respectively inherited from his mother and father. The former was unreported previously and was predicted to be likely pathogenic, whilst the latter has been reported previously and was predicted to be of uncertain significance. CONCLUSION The compound heterozygous c.13delG (p.Ala5ProfsTer68) and c.971C>T (p.Thr324Ile) variants probably underlay the disease in the proband. Above finding has enriched the spectrum of MSTO1 gene variants underlying mitochondrial myopathy and cerebellar atrophy with ataxia.
Ataxia/genetics* ; Atrophy/genetics* ; Cell Cycle Proteins/genetics* ; Child ; Cytoskeletal Proteins/genetics* ; Humans ; Infant ; Male ; Mitochondrial Myopathies ; Mutation ; Neurodegenerative Diseases ; Whole Exome Sequencing

Objective To investigate the efficacy and safety of apatinib monotherapy as subsequent-line therapy on patients with advanced ESCC. Methods We included 56 patients with advanced ESCC who were administered with apatinib monotherapy. The initial dosage of apatinib was 500mg or 250mg daily. Clinicopathological characteristics, adverse reaction and prognosis of the patients were analyzed. The primary endpoint of this study was PFS, the secondary endpoints were ORR, DCR, OS and safety of apatinib administration. Results All the 56 patients with ESCC corresponded with the eligibility criteria and were available for the evaluation of efficacy and adverse reaction. The ORR of the 56 patients who received apatinib monotherapy was 8.9% (95%CI: 3.0%-19.6%) and DCR was 64.3% (95%CI: 50.4%-76.6%). The median PFS was 3.7 months (95%CI: 3.19-4.21) and the median OS was 6.3 months (95%CI: 3.53-9.08). The common adverse reactions were hypertension (50.0%), fatigue (41.1%), loss of appetite (35.7%), hand-foot syndrome (30.4%) and diarrhea (26.8%). Conclusion Apatinib monotherapy demonstrates potential efficacy and tolerable safety as the further-line treatment for the patients with advanced ESCC. And the conclusion should be validated in prospective clinical studies subsequently.

Objective:To explore the clinical technique and method of reconstruction large soft tissue defect of plantar by skin soft tissue dilatation combined with thigh cross leg flap to improve the weight-bearing function of plantar standing.Methods:From February 2015 to June 2019, 8 cases with plantar soft tissue defects were repaired with cross leg flap expanded from the healthy side of the thigh. Right foot in 4 cases, left foot in 3 cases and bilateral in 1 case. There were 5 males and 3 females. Ages ranged from 16 to 56, with an average age of 31. Clinical features: scar ulcer in 4 cases, bone-sticking scar in 4 cases, bone exposure in 1 case. After debridement, the area of skin and soft tissue defect was 9 cm×16 cm-12 cm×29 cm, the area of harvest expanded flap was 11 cm×18 cm-14 cm×30 cm. All flaps were fixed by cross-leg with pedicle. The pedicle division were performed one month after the skin flap transmission.Results:Of the 9 flaps transferred, 8 survived, 1 died in the distal part of the flap and was repaired by secondary expanded flap, and the donor site healed in linear scar stage. After 6-24 months follow-up, the plantar flap was in good shape and could walk with weight-bearing, without ulceration, and the protective tactile sensation was gradually restored in 12 months.Conclusions:The large-area soft tissue defect of plantar was repaired with the expanded cross leg flap in the healthy thigh, which also provide sufficient thickness of soft tissue to increase the ability of bearing weight and wearing resistance of the sole. It is a good alternative method to repair large area soft tissue defect of plantar under the condition of limited transfer of perforator flap and free flap.

Objective:To investigate the variation of T, B, NK lymphocyte subgroup in children with anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis and their clinical significance.Methods:This was a prospective and control study.Forty children primarily diagnosed with anti-NMDAR encephalitis in the department of neurology in Guangzhou Women and Children′s Medical Center from January 2017 to August 2019 served as patient group, 20 healthy children served as control group.Absolute counts and percentages of T, B and NK lymphocytes in whole blood were detected before and 1 month after treatment in patient group.Serum immunoglobulin G(IgG), IgA and IgM were measured before treatment.The blood levels of T, B, NK lymphocyte subgroup were detected with flow cytometer.NMDAR antibody titers of serum and cerebrospinal fluid were detected in patient group.The differences between patient group at different time points and control group were compared.The patients were divided into two groups according to the response to treatment after 2 weeks and the absolute counts of T, B and NK lymphocytes before treatment were compared between groups.Results:Compared with control group, the blood absolute count of B lymphocyte in patient group were significantly higher before and after treatment( P<0.05). There was no significant difference of B lymphocyte in patient group between before and after treatment.After treatment, T cells(including T inhibitory cells and T helper cells)were significantly increased compared with those before treatment and those in control group( P<0.05), but there was no significant difference between patient group and control group before treatment.These with poor response to treatment after 2 weeks had higher level of B, T lymphocyte subgroup compared to those with good response( P<0.05). The level of IgG, IgA, IgM in patient group showed no significant difference with control group.There was no significant correlation between B lymphocyte count in blood and NMDAR antibody titer in cerebrospinal fluid( r=0.282, P>0.05). Conclusion:B lymphocytes increase greatly in children with anti-NMDAR encephalitis, and the level of B lymphocyte subgroup before treatment are associated with treatment response, and T lymphocytes increase greatly after treatment.There is no significant correlation between the titer of NMDAR antibody in cerebrospinal fluid and B lymphocyte level.

Objective:To explore the clinical technique and method of reconstruction large soft tissue defect of plantar by skin soft tissue dilatation combined with thigh cross leg flap to improve the weight-bearing function of plantar standing.Methods:From February 2015 to June 2019, 8 cases with plantar soft tissue defects were repaired with cross leg flap expanded from the healthy side of the thigh. Right foot in 4 cases, left foot in 3 cases and bilateral in 1 case. There were 5 males and 3 females. Ages ranged from 16 to 56, with an average age of 31. Clinical features: scar ulcer in 4 cases, bone-sticking scar in 4 cases, bone exposure in 1 case. After debridement, the area of skin and soft tissue defect was 9 cm×16 cm-12 cm×29 cm, the area of harvest expanded flap was 11 cm×18 cm-14 cm×30 cm. All flaps were fixed by cross-leg with pedicle. The pedicle division were performed one month after the skin flap transmission.Results:Of the 9 flaps transferred, 8 survived, 1 died in the distal part of the flap and was repaired by secondary expanded flap, and the donor site healed in linear scar stage. After 6-24 months follow-up, the plantar flap was in good shape and could walk with weight-bearing, without ulceration, and the protective tactile sensation was gradually restored in 12 months.Conclusions:The large-area soft tissue defect of plantar was repaired with the expanded cross leg flap in the healthy thigh, which also provide sufficient thickness of soft tissue to increase the ability of bearing weight and wearing resistance of the sole. It is a good alternative method to repair large area soft tissue defect of plantar under the condition of limited transfer of perforator flap and free flap.