The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Objective To explore the correlation of CPNE3 expression with long-term prognosis of patients with gastric cancer(GC)and the possible mechanism.Methods We retrospectively collected the data of 104 GC patients undergoing radical surgery in our hospital from February,2013 to October,2017.TCGA database and immunohistochemistry were used to analyze CPNE3 expression level in GC tissues and its effects on tumor progression and long-term prognosis of the patients.GO analysis was performed to predict the biological role of CPNE3 in GC.We also conducted cell experiments with MGC803 cells and observed the effects of CPNE3 knockdown,CPNE3 overexpression and LY294002(a PI3K/AKT inhibitor)treatment on cell apoptosis and cellular expressions of apoptotic proteins using flow cytometry and Western blotting.Results TCGA analysis and immunohistochemistry both showed high expressions of CPNE3 in GC(P<0.05).The patients with high CPNE3 expressions had a reduced 5-year survival(P<0.01),and a high CPNE3 expression,CEA level≥5 μg/L,CA19-9 level≥37 kU/L,T3-T4 stage,and N2-N3 stage were all independent risk factors for a lowered 5-year survival rate after surgery.The sensitivity and specificity of CPNE3 for predicting 5-year mortality was 79.59%and 74.55%,respectively(P<0.05).GO analysis predicted that CPNE3 negatively regulated GC cell apoptosis.In MGC803 cells,CPNE3 knockdown significantly increased cell apoptosis,enhanced Bax and Cleaved Caspase-3 expressions and decreased Bcl-2 expression,while CPNE3 overexpression produced the opposite results(P<0.05).The cellular expressions of p-PI3K and p-AKT were significantly decreased following CPNE3 knockdown and increased following CPNE3 overexpression(P<0.05).Treatment with LY294002 obviously attenuated the inhibitory effect of CPNE3 overexpression on apoptosis of MGC803 cells(P<0.05).Conclusion CPNE3 is highly expressed in GC tissues and affects the long-term prognosis of the patients possibly by inhibiting GC cell apoptosis through activation of PI3K/AKT signaling.

Objective To explore the correlation of CPNE3 expression with long-term prognosis of patients with gastric cancer(GC)and the possible mechanism.Methods We retrospectively collected the data of 104 GC patients undergoing radical surgery in our hospital from February,2013 to October,2017.TCGA database and immunohistochemistry were used to analyze CPNE3 expression level in GC tissues and its effects on tumor progression and long-term prognosis of the patients.GO analysis was performed to predict the biological role of CPNE3 in GC.We also conducted cell experiments with MGC803 cells and observed the effects of CPNE3 knockdown,CPNE3 overexpression and LY294002(a PI3K/AKT inhibitor)treatment on cell apoptosis and cellular expressions of apoptotic proteins using flow cytometry and Western blotting.Results TCGA analysis and immunohistochemistry both showed high expressions of CPNE3 in GC(P<0.05).The patients with high CPNE3 expressions had a reduced 5-year survival(P<0.01),and a high CPNE3 expression,CEA level≥5 μg/L,CA19-9 level≥37 kU/L,T3-T4 stage,and N2-N3 stage were all independent risk factors for a lowered 5-year survival rate after surgery.The sensitivity and specificity of CPNE3 for predicting 5-year mortality was 79.59%and 74.55%,respectively(P<0.05).GO analysis predicted that CPNE3 negatively regulated GC cell apoptosis.In MGC803 cells,CPNE3 knockdown significantly increased cell apoptosis,enhanced Bax and Cleaved Caspase-3 expressions and decreased Bcl-2 expression,while CPNE3 overexpression produced the opposite results(P<0.05).The cellular expressions of p-PI3K and p-AKT were significantly decreased following CPNE3 knockdown and increased following CPNE3 overexpression(P<0.05).Treatment with LY294002 obviously attenuated the inhibitory effect of CPNE3 overexpression on apoptosis of MGC803 cells(P<0.05).Conclusion CPNE3 is highly expressed in GC tissues and affects the long-term prognosis of the patients possibly by inhibiting GC cell apoptosis through activation of PI3K/AKT signaling.

DNA/metabolism* ; Gene Editing ; HEK293 Cells ; Humans

Objective To investigate the health-related quality of life and its relative factors in children with leukemia during maintenance treatment period. Therefore, the basis for effective individualization intervention can be provided. Methods A total of 224 leukemia children in maintenance treatment were collected in Affiliated Children′s Hospital of Chongqing Medical University from October 2015 to January 2016 by convenience sampling methods, questionnaire was used to assess the physical status, emotional status, social status, school status of the children. Results Single factor and generalized linear regression analysis were used to conclude that patient′s age (F=5.841-36.343, all P<0.01), parenting pattern (F=4.006-4.288, all P<0.05), family economic status (F=3.277-15.865, P<0.05 or 0.01) and the caregivers′information mastery level household location (F=2.044-2.661, P<0.05 or 0.01) had significant influence on the quality of life of children with leukemia in maintenance treatment. Conclusions The health-related quality of life and its relative factors in children with leukemia during maintenance treatment period should be analysis comprehensively. At the same time, take intervention should be taken from physiology, psychology, society, and school, to improve the social adaptability of children with leukemia and help them return to society as soon as possible.

Objective To evaluate the role of neuron-restrictive silencer factor (NRSF) in the spinal cord in remifentanil-induced hyperalgesia in a mouse model of incisional pain (IP) .Methods Fifty-six male Kunming mice were randomly divided into 7 groups (n=8 each):control group (group C) ,IP group (group I) ,IP +remifentanil group (group IR ) , NRSF antisense oligonucleotide group (NAS group ) , IP + NRSF antisense oligonucleotide group (I+NAS group ) ,IP + remifentanil + NRSF mismatch oligonucleotide group (IR+NMS group) , and IP + remifentanil + NRSF antisense oligonucleotide group (IR + NAS group ) . Artificial cerebrospinal fluid 5 μl was injected intrathecally once a day for 3 consecutive days in C ,I and IR groups .NRSF antisense oligonucleotide NAS 10μg was injected intrathecally once a day for 3 consecutive days in NAS ,I+NAS and IR + NAS groups . NRSF mismatch oligonucleotide 10 μg was injected intrathecally once a day for 3 consecutive days in IR+NMS group .A 1-cm longitudinal incision was made through skin ,fascia and muscle of the plantar aspect of the right hindpaw to establish the model of incisional pain in sevoflurane-anesthetized rats .At 30 min after the last injection ,normal saline 0.4 ml was infused subcutaneously in C and NAS groups ,the model was established and normal saline 0.4 ml was subcutaneously infused simultaneously in I and I+NAS groups ,and the model was established and remifentanil 0.04 mg/kg was subcutaneously infused simultaneously in IR ,IR+NMS and IR+NAS groups .At 3 days before operation (T0 ) ,4 h before operation (T1 ) and 4 ,12 ,24 and 48 h after operation (T1-5 ) ,mechanical paw withdrawal threshold to von Frey stimuli (PMWT ) and paw withdrawal latency to thermal nociceptive stimulus (PTWL ) were measured .Results Compared with C group ,the PWMT and PWTL were significantly decreased at T2-5 in I ,IR ,I+NAS ,IR+NMS and IR+NAS groups ( P<0.05) ,and no significant change was found in the PWMT and PWTL at each time point in NAS group ( P>0.05 ) .Compared with I group ,the PWMT and PWTL were significantly decreased at T2-5 in IR and IR+NMS groups ( P<0.05) , and no significant change was found in the PWMT and PWTL at each time point in I +NAS group ( P>0.05) . Compared with IR group ,no significant change was found in the PWMT and PWTL at each time point in IR+NMS group ( P>0.05) ,and the PWMT and PWTL were significantly increased at T2-5 in IR+NAS group ( P<0.05) . Conclusion NRSF in the spinal cord is involved in the development and maintenance of hyperalgesia induced by remifentanil in a mouse model of IP .

Objective To investigate the effects of repeated intrathecally kinesin superfamily protein 17 (KIF17) antisense oligodeoxynucleotide (ODN) on the expression of mLin10 and NR2B in spinal cord in a mouse model of bone cancer pain.Methods Fifty-six male C3H/HeJ mice,aged 4 ～ 6 weeks,weighting 20 ～ 25 g,were randomly divided into two groups:sham operation group (group S,n=20) and bone cancer pain group (group T,n=36).20μl α-minimal essence medium (α-MEM) which containing 2× 105 NCTC2472 osteosarcoma cells was injected into the intramedullary space of the right femur in group T.In group S,no cancer cell was instead.The number of spontaneous flinches (NSF) and the paw withdrawal mechanical threshold (PWMT) were measured at the day before (base) and the days 4,7,10 and 14 after inoculation.According to the corresponding time points,twenty-four mice were sacrificed for determination the expression of KIF17,mLin10 and NR2B using Western blot.Then,the mice of group T were randomly divided into three groups (n=8,T1,T2,T3,group).In group S and group T1,Saline 5 μl was injected intrathecally.KIF17 sense ODN and antisense ODN,5 μg/5μl were respectively injected in group T2 and T3 for 6 consecutive days.Pain behaviors were assessed at the days 2-6 after the first injection.And determinated the KIF17,mLin10 and NR2B expression,again.Results Compared with group S,the NSF was increased and the PWMT was decreased at the days 7,10 and 14 after inoculation in group T (P＜0.05).Compared with the base ((0.65±0.15),(1.06±0.06),(1.01±0.14)),the expression of KIF17,mLin10 and NR2B (14d:(1.13 ±0.06),(2.17 ± 0.37),(1.85 ± 0.32)) were increased at the days 7,10 and 14 after inoculation in group T(P＜0.05).During the course of the injection,compared with group T1 and T2,the NSF was decreased and the PWMT was increased significantly in the group T3(P＜0.05),the expression of KIF17,mLin10 and NR2B((0.88±0.08),(0.96±0.11),(1.03±0.08)) were reduced in group T3 (P＜0.05).Conclusion Intrathecal KIF 17 antisense ODN in the mice of bone cancer pain improves the pain behaviors,and inhibits the up-regulated of KIF17,mLin10 and NR2B during the course of the injection.

Objective To investigate the effects of intrathecal injection of α-cyano-4-hydroxy-cinnamate (4-CIN) in rats with neuropathic pain induced by chronic constriction injury of sciatic nerve (CCI).Methods Eighteen male SD rats were divided randomly into 3 groups(n=6):sham group (group S),CCI model group (group C0) and 4-CIN group (group C1).Group C0 and C1 were operated with the model of neuropathic pain induced by chronic constriction injury of sciatic nerve ; and group S were treated as sham operated rats.Two days after operation,group C1 received intrathecal injection of 100 μmol 4-CIN dissolved in 10％ DMSO 10 μl,while group C0 received intrathecal injection of 10％ DMSO 10 μl only.The paw withdrawal thermal latency(PWTL) and paw withdrawal mechanical threshold(PWMT) were tested 1 d before operation and 1 d,3 d,7 d,10 d,14 d after operation(T0-5).Results The basic values of PWMT and PWTL before operation showed no statistically significant differences among the three groups.On T1-5,the PWMT((11.71 ±2.81) g,(9.76± 1.00) g,(8.22± 1.33) g,(6.50± 1.48) g,(4.67± 1.03) g) and PWTL((11.36±2.18) s,(11.60±2.54) s,(8.54± 1.42) s,(7.59± 1.00) s,(6.88± 0.42) s) in group C0 were significantly lower than those in group S (P＜0.05).However,there were no significant differences between group S and C1 on T2-5(P＞0.05).Conclusion Intrathecal administration of 4-CIN can attenuate neuropathic pain in rats induced by CCI.

OBJECTIVE: To determine the changes of Mu-opioid receptor (Mor) and neuron-restrictive silencer factor (NRSF) in periaquductal gray (PAG) in mouse models of remifentanil-induced postoperative hyperalgesia. METHODS: Thirty-two Kun-Ming mice were randomly divided into 4 groups (8 mice in each group): Group C (mice underwent a sham procedure and saline was infused subcutaneously over a period of 30 min), Group I (mice underwent a surgical incision and the same volume of saline), Group R (mice underwent a sham procedure and remifentanil was infused subcutaneously at the moment of surgical incision over a period of 30 min), and group IR (mice underwent a surgical incision and remifentanil). Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) tests were performed 24 h before the operation and 2, 6, 24, and 48 h after the operation. The specimens were collected after behavioral testings at 48 h. The expressions of Mor and NRSF in mice's PAG neurons were determined by Western blot. RESULTS: Mechanical allodynia and thermal hyperalgesia developed in Group I, R and IR (P<0.01). Intraoperative infusion of remifentanil enhanced mechanical allodynia and thermal hyperalgesia in mice with planta incision (P<0.01). In Group R and Group IR, the expression of Mor was significantly lower (P<0.01) and NRSF was significantly higher (P<0.01) when compared with Group C and Group I. CONCLUSION Intraoperative infusion of remifentanil induces postoperative hyperalgesia in mouse models, accompanied with decreased expressions of Mor and increased of NRSF level in PAG neurons, which may be involved in remifentanil induced hyperalgesia.
Animals ; Disease Models, Animal ; Hyperalgesia ; chemically induced ; Mice ; Pain, Postoperative ; Periaqueductal Gray ; drug effects ; metabolism ; Piperidines ; administration & dosage ; Receptors, Opioid, mu ; metabolism ; Remifentanil ; Repressor Proteins ; metabolism

Identification of the function of all genes in the mammalian genome is critical in understanding basic mechanisms of biology. However, the diploidy of mammalian somatic cells has greatly hindered efforts to elucidate the gene function in numerous biological processes by mutagenesis-based genetic approaches. Recently, mouse haploid embryonic stem (haES) cells have been successfully isolated from parthenogenetic and androgenetic embryos, providing an ideal tool for genetic analyses. In these studies, mouse haES cells have already shown that they could be used in cell-based forward or reverse genetic screenings and in generating gene-targeting via homologous recombination. In particular, haES cells from androgenetic embryos can be employed as novel, renewable form of fertilization agent for yielding live-born mice via injection into oocytes, thus showing the possibility that genetic analysis can be extended from cellular level to organism level.
Animals ; Embryonic Stem Cells ; cytology ; metabolism ; Genetic Techniques ; Genome ; Haploidy ; Models, Animal ; Mutagenesis ; Parthenogenesis