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 evaluate the detection ability and efficiency of single nucleotide polymorphisms array (SNP-array) and next generation sequencing (NGS) in preimplantation genetic testing (PGT).Methods:Totally 188 couples who carried pathogenic gene mutation and requested preimplantation genetic testing for monogenic (PGT-M) treatment were retrospectively analyzed in the Reproductive Center of Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region during January 2020 and August 2022. After ovulation induction, insemination was conducted by intracytoplasmic sperm injection (ICSI) and cultured in vitro, 995 blastocysts were harvested and biopsied. After whole genome amplification (WGA) of the genetic material from embryonic cell samples, their carrying status of mutations and chromosome copy number variations (CNVs) were analyzed by SNP-array or NGS, respectively, and along with mutation direct detection by Sanger sequencing or Gap-PCR. The relationship between female age and the number of blastocysts was analyzed, as well as the proportion of embryos carrying mutations and pathogenic CNVs. The detection success rate and accuracy of different molecular diagnostic techniques used in PGT were compared. Amniocentesis prenatal diagnosis was performed in the second trimester after successful intrauterine transfer of embryos. Results:1) A total of 924 embryo samples were successfully performed genetic testing, with a total success rate of 92.9%, and 389 embryos (42.1%) can be transferred according to these results. 2) In detecting deletional α-thalassemia, the success rate of Gap-PCR [84.9% (465/548)] was lower than that of SNP-array [98.7% (81/82)] and NGS [92.5% (431/466)]. However, the success rate of direct mutation detection by Sanger sequencing [98.5% (440/447)] was not significantly different from that by SNP-array [95.6% (110/115)] and NGS [96.1% (319/332)]. There were 38 embryo samples with direct mutation detection results inconsistent with those based on SNP haplotyping. In addition, 4 embryo samples failed SNP haplotyping due to chromosomal recombination. 3) Compared with NGS, SNP-array had a lower success rate [83.7% (165/197)] in detecting CNVs, but it could find out more types of chromosomal abnormalities. 4) A total of 152 embryo transfers were performed, 107 patients got clinical pregnancies, 69 patients completed amniocentesis prenatal diagnosis, and 42 healthy infants were delivered.Conclusion:In considering the detection efficiency, SNP-array is suitable for analyzing embryos which carry multiple pathogenic genes, rare monogenic or deletion mutations, whereas NGS is suitable for detecting common types of mutations. Meanwhile, using Sanger sequencing and Gap-PCR to directly detect the mutations can improve the success rate and accuracy of PGT. Our findings would provide a basis for PGT technicians to select appropriate detection platforms based on the type of mutations and the situation of patients.

Objective:To evaluate the detection ability and efficiency of single nucleotide polymorphisms array (SNP-array) and next generation sequencing (NGS) in preimplantation genetic testing (PGT).Methods:Totally 188 couples who carried pathogenic gene mutation and requested preimplantation genetic testing for monogenic (PGT-M) treatment were retrospectively analyzed in the Reproductive Center of Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region during January 2020 and August 2022. After ovulation induction, insemination was conducted by intracytoplasmic sperm injection (ICSI) and cultured in vitro, 995 blastocysts were harvested and biopsied. After whole genome amplification (WGA) of the genetic material from embryonic cell samples, their carrying status of mutations and chromosome copy number variations (CNVs) were analyzed by SNP-array or NGS, respectively, and along with mutation direct detection by Sanger sequencing or Gap-PCR. The relationship between female age and the number of blastocysts was analyzed, as well as the proportion of embryos carrying mutations and pathogenic CNVs. The detection success rate and accuracy of different molecular diagnostic techniques used in PGT were compared. Amniocentesis prenatal diagnosis was performed in the second trimester after successful intrauterine transfer of embryos. Results:1) A total of 924 embryo samples were successfully performed genetic testing, with a total success rate of 92.9%, and 389 embryos (42.1%) can be transferred according to these results. 2) In detecting deletional α-thalassemia, the success rate of Gap-PCR [84.9% (465/548)] was lower than that of SNP-array [98.7% (81/82)] and NGS [92.5% (431/466)]. However, the success rate of direct mutation detection by Sanger sequencing [98.5% (440/447)] was not significantly different from that by SNP-array [95.6% (110/115)] and NGS [96.1% (319/332)]. There were 38 embryo samples with direct mutation detection results inconsistent with those based on SNP haplotyping. In addition, 4 embryo samples failed SNP haplotyping due to chromosomal recombination. 3) Compared with NGS, SNP-array had a lower success rate [83.7% (165/197)] in detecting CNVs, but it could find out more types of chromosomal abnormalities. 4) A total of 152 embryo transfers were performed, 107 patients got clinical pregnancies, 69 patients completed amniocentesis prenatal diagnosis, and 42 healthy infants were delivered.Conclusion:In considering the detection efficiency, SNP-array is suitable for analyzing embryos which carry multiple pathogenic genes, rare monogenic or deletion mutations, whereas NGS is suitable for detecting common types of mutations. Meanwhile, using Sanger sequencing and Gap-PCR to directly detect the mutations can improve the success rate and accuracy of PGT. Our findings would provide a basis for PGT technicians to select appropriate detection platforms based on the type of mutations and the situation of patients.

Colorectal cancer (CRC) is a common malignant tumor of the digestive tract, which seriously threatens human health. In recent years, many studies have found that Fusobacterium nucleatum (Fn) is positively related to the occurrence of CRC. In the process of CRC carcinogenesis, Fn can play an important role by inducing the expression of pro-inflammatory cytokines and triggering chronic inflammation, inhibiting the function of immune cells, inducing chemotherapy resistance, promoting the expressions of tumor genes and microRNAs and regulating glycolysis.

Objective:To evaluate the effect of intrathecal insulin-like growth factor-1 (IGF-1) on chemotherapy-induced neuropathic pain (NP) in mice.Methods:Forty clean-grade healthy male C57 mice, aged 7-9 weeks, weighing 22-24 g, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), chemotherapy-induced NP group (group CIPN), low-dose IGF-1 group (group I1) and high-dose IGF-1 group (group I2). In CIPN, I1 and I2 groups, oxaliplatin 5 mg/kg was intraperitoneally injected for 5 consecutive days to establish chemotherapy-induced NP model.Normal saline 0.2 ml was given in group C. After measurement of the pain threshold at 10 days after establishment of the model, IGF-1 0.5 and 1.0 μg were intrathecally injected in group I1 and group I2, respectively.Normal saline 5 μl was intrathecally injected in C and CINP groups.Mechanical withdrawal threshold (MWT) was measured at 3, 5, 8, 10, 11, 13 and 15 days after establishment of the model.After measurement of the pain threshold at 15 days after establishment of the model, the expression of spinal IGF-1, IGF-1receptor (IGF-1R), interleukin (IL)-17A, IL-1β and tumor necrosis factor (TNF)-α was detected, and IGF-1 positive cells were counted using immunofluorescence. Results:Compared with group C, MWT was significantly decreased, the expression of spinal IGF-1 was down-regulated, the count of IGF-1 positive cells was decreased, and expression of IL-17A, IL-1β and TNF-α was up-regulated at 3-25 days after establishment of the model in CINP, I1 and I2 groups ( P<0.05). Compared with group CIPN, MWT was significantly increased at 15 days after establishment of the model in group I1, and MWT was increased, the expression of spinal IGF-1 was up-regulated, the count of IGF-1 positive cells was increased, and expression of IL-17A, IL-1β and TNF-α was down-regulated at 13 and 15 days after establishment of the model in group I2 ( P<0.05). Compared with group I1, the count of IGF-1 positive cells in spinal dorsal horn was increased in group I2 ( P<0.05). There was no significant difference in the expression of spinal IGF-1R among the 4 groups ( P>0.05). Conclusion:Intrathecal IGF-1 can alleviate chemotherapy-induced NP, and the mechanism may be related to inhibiting the inflammatory responses in spinal cord of mice.

Objective: To screen, diagnose and follow up the abnormal mutation in the gene screening of neonatal deafness. Methods: A total of 24161 newborns born in Zhuhai Maternal and Child Health Hospital from February 1, 2015 to January 31, 2008 were screened for hearing and deafness genes, and audiological screening, diagnosis and 1-3 years follow-up were carried out for the newborns with positive gene screening. Results: There were 991 cases of deafness gene mutation (533 males and 458 females), and the rate of abnormal mutation was 4.10%(991/24 161). Among them, 921 cases were single heterozygous mutation, 130 cases were failed in primary hearing screening, 11 cases were failed in secondary hearing screening, 8 cases were abnormal in audiological diagnosis finally. In these 8 cases, 3 were diagnosed as otitis media and passed audiological follow-up after cure, 2 cases of single ear sensorineural injury caused by high-risk factors, passed after close audiological follow-up, and the other 3 cases were closely audiological follow-up while none of them were successfully sequenced. All of them were moderate to severe sensorineural deafness, 1 case was heterozygous mutation at 3 loci of GJB2(c.235delC,c.408C>A,c.134G>A), 1 case was heterozygous mutation at 2 loci of GJB2(c.235delC, c.109G>A), and 1 case was single heterozygous mutation of GJB2(c.235delC). The remaining 913 cases who passed the primary screening, secondary screening or hearing diagnosis were followed up for 1 to 3 years. Three cases of multiple heterozygous mutation were found in gene screening(2 cases were SLC26A4 2168A>G, IVS7-2A>G, 1 case was GJB2 c.176_191del 16bp, c.299_300del AT), all of them passed both primary and secondary hearing screening. In these 3 cases, the final audiological diagnosis was moderate sensorineural deafness in both ears, with no improvement in the follow-up of 1-3 years. There were 9 monogenic homozygous mutations, 7 failed in primary hearing screening, 3 failed in secondary hearing screening and also failed in audiological diagnosis and 1-3 years′ audiological follow-up, all of whom were GJB2 c.235 del C homozygous mutations, and one of whom had a definite family history of deafness. The remaining 6 cases of homozygous mutation diagnosed by primary screening, secondary screening or hearing diagnosis were GJB2 c109G>A homozygous mutation, and passed the 1-3 years′ hearing follow-up. 58 children with mtDNA mutations, including 2 with 12S rRNA 1494C>T homozygous mutation, 47 with 1555A>G homozygous mutation, and 9 with 1555A>G heterozygous mutation, all passed the primary or secondary hearing screening, and were instructed to ban ototoxic drugs for the whole life, and passed the 1-3 years′ hearing follow-up. Conclusions The audiological follow-up of children with monogenic heterozygous mutations in deafness gene screening is generally normal. In case of abnormality, the influencing factors such as otitis media should be excluded at first. In case of unexplained moderate to severe sensorineural deafness, the whole-gene sequencing should be performed to find possible pathogenic factors. The children with homozygous mutation or compound heterozygous mutation in gene screening, most of whom show different degrees of hearing loss, should be followed up for a long time, and provide parents with scientific and reasonable genetic counseling according to the mutation genes and loci,. The hearing of drug-induced deafness gene carriers is normal after birth. Parents should be advised to strengthen prevention and follow-up is generally enough.

To analyze and research the number and size of public hospitals of our country at the present stage, and explore the regional health planning of public hospitals under the background of China's new medical reform, provide the scientific basis for our further layout of regional health planning for public hospitals of our country. Methods Mainly use the method of the document analysis, by collecting and analyzing the literature related to the regional health planning of public hospitals under the new health reform. And relevant data on China Health Statistics Yearbook 2011 were analyzed. Results The irrational regional health planning and layout design of public hospitals not only seriously affect the efficiency of health care resources, but also exacerbate the difficulty and high cost of people getting medical service. Conclusion Under the new health care reform, the definition of public hospitals and the positioning and functionality of public hospitals need to be re-examined. The following three aspects will solve the problem of regional health planning of public hospitals. First, to moderately reduce the number and size of public hospitals; second, to determine and adjust the number of public hospitals at all levels; Third, to reasonably lay out urban and rural public hospital.

Objective To evaluate the effect of intrathecal cardamonin on diabetic neuropathic pain (DNP) in rats.Methods Healthy adult male Sprague-Dawley rats,aged 2 months,weighing 180-220 g,were included in the study.Diabetes mellitus was produced by intraperitoneal injection of streptozotocin 60 mg/kg after intrathecal catheterization.When decrease in pain threshold＞50％ of the baseline at 21 days after diabetes mellitus was produced,the induction of DNP was considered successful.Twenty-four rats with DNP were divided into 4 groups (n=6 each) using a random number table:group DNP,rapamycin group (group R),cardamonin 50 μg group (group D50) and cardamonin 100 μg group (group D100).Another 6 healthy age-matched rats were used as normal control (group C).In DNP,R,D50 and D100 groups,dimethyl sulfoxide 10 μl,rapamycin 5 μg and cardamonin 50 μg and 100 μg were intrathecally injected,respectively,once a day for 7 consecutive days starting from 21 days after successful estabiishment of the model.Mechanical paw withdrawal threshold (MWT) was measured before establishment of the model,on 7,14 and 21 days after establishment of the model,and on 1,4 and 7 days after intrathecal injection.The rats were sacrificed after the last MWT measurement,and their L3-5 segments of the spinal cord were removed for determination of the expression of S6K,p-S6K and synapsin Ⅱ by Western blot.Results Compared with group C,MWT was significantly decreased,and the expression of spinal S6K,p-S6K and synapsin Ⅱ was up-regulated in group DNP (P＜0.05 or 0.01).Compared with group DNP,MWT was significantly increased,and the expression of spinal S6K,p-S6K and synapsin Ⅱ was down-regulated in R,D50 and D100 groups (P＜0.05 or 0.01).Compared with group D50,MWT was significantly increased,and the expression of spinal S6K,p-S6K and synapsin Ⅱ was down-regulated in group D100 (P＜0.05).Conclusion Intrathecal cardamonin can relieve DNP in rats,and the mechanism is related to inhibiting spinal mammalian target of rapamycin activity and down-regulating the expression of synapsin Ⅱ.

AIM:To investigate the potential role of Sonic hedgehog (Shh) signaling pathways in the radioresistance of esophageal cancer.METHODS:Radioresistant cell line Eca109R was established by repeating X-ray irradiation at dose of 60 Gy in total using Eca109 cells as parental cells.The radiosensitivity of the parental and radioresistant cells was confirmed by colony formation assay.The cell viability was detected by CCK-8 assay.The intracellular protein levels of Shh and Gli1 were determined by Western blot and immunofluorescence.RESULTS:The survival fractions at dose of 2 Gy for Eca109R cells and Eca109 cells were 0.937±0.013 and 0.499±0.042, respectively.The inhibitory rate of cell viability decreased gradually in the Eca109R cells (P<0.05), suggesting that the radioresistant cell line was successfully established.The results of Western blot indicated that the protein expression of Shh and Gli1 was much higher in the Eca109R cells than that in the Eca109 cells (P<0.05).Immunofluorescence staining showed that Gli1 was expressed in the cytoplasm and nucleus, and presented nuclear clustering in the Eca109R cells.The positive rate of Gil1 expression in Eca109 cells was 52.3%± 0.035%, while that in Eca109R cells was 87.6%±0.021% (P<0.05).CONCLUSION:The radioresistance of esophageal cancer may be related to the activation of Shh signaling pathways with over-expression of Gli1 and other related proteins.

Objective To investigate the effect of propofol on human renal tubule epithelial cell (HK-2 cells) fibrosis induced by ATP depletion/recovery and the role of transforming growth factor β activated kinase 1 (TAK1) in it.Methods HK-2 cells were seeded in 96-well plates,and randomly divided into 4 groups (n =36 each) using a random number table:control group (group C),ATP depletion/recovery group (group D/R),propofol group (group P),and TAK1 over-expression group (group T).HK-2 cells were exposed to antimycin A for 1 h and then returned to normal culture medium to establish the model of ATP depletion/recovery-induced injury.At 1 h before ATP depletion,the cells were incubated for 1 h in the DMEM liquid culture medium containing propofol with the final concentration of 20 μmol/L in group P,and the cells were incubated for 1 h in the DMEM liquid culture medium containing propofol with the final concentration of 20 μmol/L and TAK1 with the titer of 2× 107 TU/ml in group T,and the other treatments were similar to those previously described in group D/R.At 12 h after ATP recovery,the cell viability was evaluated by methyl thiazolyl tetrazolium assay,and cell apoptosis was detected using TUNEL and scored.The expression of TAK1 was detected using Western blot at 12,24 and 48 h after ATP recovery.The expression of α-smooth muscle actin (αSMA),fibronectin (FN),and collagen protein 1 (COL1) was measured at 48 h after ATP recovery.Results Compared with group C,the cell viability was significantly decreased,the apoptosis score was increased,and the expression of TAK1,COL1,αSMA and FN was up-regulated after ATP recovery in D/R,P and T groups (P＜0.05).Compared with group D/R,the cell viability was significantly increased,the apoptosis score was decreased,and the expression of TAK1,COL1,αSMA and FN was down-regulated after ATP recovery in P and T groups (P＜0.05).Compared with group P,the cell viability was significantly decreased,the apoptosis score was increased,and the expression of TAK1,COL1,αSMA and FN was up-regulated after ATP recovery in group T (P＜ 0.05).Conclusion Propofol can reduce HK-2 cell fibrosis induced by ATP depletion/recovery,and the mechanism may be related to down-regulation of TAK1 expression.