Objective This study aimed to identify PAX9 variants in non-syndromic tooth agenesis families of Chi-na,as well as to analyze the genotype-phenotype of non-syndromic tooth agenesis caused by PAX9 variants,which can provide a basis for the genetic diagnosis of tooth agenesis.Methods We collected the data of 44 patients with non-syn-dromic oligodontia who underwent treatment at Stomatological Hospital of Hebei Medical University between 2018 and 2023.Whole-exome sequencing was performed on the peripheral blood of the proband and its core family members,and the variants were verified by Sanger sequencing.Pathogenicity analysis and function prediction of the variants were per-formed using bioinformatics tools.The correlation between the genotype of PAX9 variant and its corresponding pheno-type was examined by reviewing 55 publications retrieved from PubMed.The studies involved 232 tooth agenesis pa-tients with PAX9 variants.Results A novel PAX9 c.447delG(p.Pro150Argfs*62)and a reported PAX9 c.406C>T(p.Gln136*)were identified in two Chinese families.Through bioinformatics analysis and three-dimensional structural mod-eling,we postulated that the frameshift variant was pathogenic.The outcome was the premature cessation of PAX9 pro-tein,which caused severe structural and functional deficiencies.Summarizing the PAX9 genotype-phenotype relationship revealed that patients carrying the PAX9 variant commonly led to loss of the second molars.Conclusion We identified the novel PAX9 c.447delG(p.Pro150Argfs*62)in a Chinese family of non-syndromic oligodontia,expanding the known variant spectrum of PAX9.The most susceptible tooth position for PAX9 variants of tooth agenesis was the second mo-lars and the deciduous molars during the deciduous dentition.

Objective:To evaluate the efficacy and safety of Chinese medicine Jianpi Antai formula in infertile women undergoing in vitro fertilization-embryo transfer(IVF-ET).Methods:A total of 300 infertile women who underwent 2 frozen embryo transfer procedures at the Reproductive Medicine Center,Sir Run Run Shaw Hospital were included in the study.The participants were randomly divided into study group and control group.The study group received routine medication plus the Jianpi Antai formula during the period of embryo transfer,while the control group received routine medication only.The general condition,embryo implantation rate,clinical pregnancy rate,live birth rate,and the blood routine and liver and kidney function were evaluated and compared between two groups.Results:There were 277 cases who completed the study,including 134 in the study group and 143 in the control group.The embryo implantation rate(68.7%vs.55.9%),the clinical pregnancy rate(56.7%vs.44.8%)and the live birth rate(50.7%vs.37.8%)in the study group were all higher than those in the control group(all P＜0.05).Subgroup analysis revealed that in patients of advanced age(≥35 years)and those with decreased ovarian reserve function(anti-Müllerian hormone＜1.68 ng/mL),the embryo implantation rate,clinical pregnancy rate,and live birth rate in the study group were all higher than those in the control group(all P＜0.05).During the follow-up period,there were no abnormalities in the basic vital signs of both groups,and no adverse events were reported.Conclusion:Jianpi Antai formula can safely improve the embryo implantation rate in infertile women undergoing IVF-ET,reduce the embryo miscarriage rate,increase the live birth rate as well as improve the clinical outcomes.

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.
Female ; Humans ; Pregnancy ; Blood Glucose/metabolism* ; Diabetes, Gestational/metabolism* ; Glucose/metabolism* ; Melatonin/metabolism* ; Polymorphism, Genetic ; PPAR gamma ; Receptor, Melatonin, MT2/genetics*

Based on a research on judicial cases concerning the authenticity of electronic medical records in the past three years, the authors encountered judicial dilemmas in judicial practice. The challenges arise due to the special manifestations of electronic medical records, unclear and disputable criteria for the authenticity of electronic medical records, low application level of electronic medical records identification, and inconsistent responsibility attribution. In order to effectively apply the electronic medical record system, it is recommend to promote pre-litigation prevention by unifying the construction standards of the computerized patient record system, strengthening hospital electronic medical record management and entrusting third-party storage to ensure the evidential weight. In addition, it is necessary to establish standards for authenticity of medical records, improve the electronic medical record forensic identification system and clarify the attribution of the responsibility for untrue medical records, so as to improve the handling of such medical damage cases during litigation.

With the rapid development of " Internet+ healthcare" , medical data has gained an ever important role. How to determine the reasonable use boundary of medical data and leverage its supporting role, has grown an urgent problem to be solved. The authors analyzed the characteristics of medical data, and held that medical data is not equivalent to information, as it does not have the characteristics of legal objects in nature. In addition, it lacks originality. Therefore it is difficult to protect through the existing rights system. However, due to its property interest and personality, the authors tried to establish a new right for protection. In the construction of such medical data right, the authors claimed that patients should be the subject of the right, and medical institutions can appropriately restrict the freedom of patients′ through reasonable use rules and legal licensing system. In this way, we can not only promote medical data sharing and the development of social health, but also fully protect the legitimate rights and interests of patients.

Objective: To investigate the sonographic characteristics of papillary thyroid microcarcinoma(PTMC) and the preoperative prediction value for cervical lymphatic metastasis of PTMC. Methods: Three hundred and fifty-eight PTMC patients who were confirmed by pathology and accepted partly or totally thyroidectomy and neck dissection were collected to analyze the sonographic characteristics, all patients were classified according to multifocal carcinoma nodules and solitary carcinoma nodules; cervical lymphatic metastasis or not; the maximum diameter of carcinoma nodules. Univariate analysis and Logistic regression analysis were used. Results: Compared with solitary PTMC, multifocal PTMC was prone to emerge blood flow signals, heterogeneity, cervical lymphatic metastasis(all P<0.05). By univariate analysis, the risk factors of cervical lymphatic metastasis in PTMC were multifocal lesions and the total maximum diameter >1 cm, irregular edge, irregular shape, microcalcification, capsular invasion(all P<0.05). With Logistic regression analysis, the independent risk factors of cervical lymphatic metastasis in PTMC were multifocality and capsular invasion. Combining multifocality and capsular invasion, which area under the ROC(AUC) was 0.807. Conclusions Combining multifocality and capsular invasion significantly improves the risk of cervical lymphatic metastasis in PTMC by ultrasonography.

It is difficult for the patients with low cure rate to achieve the requirements of the"but for rule"or "preponderance of evidence standard" in the traditional causal argument. In dealing with such cases ,judicial practice has tried to broaden the concept of damage ,and adopt the theories of"loss of chance" ,"expectation infringement theory"or"comparative possibility theory" ,with the purpose to make up for the applicable dilemma of traditional causality. However ,the expansion of the concept of the damage will objectively cause some problems like abuse of rights ,concrete right becoming nothing and even subjective imputation.In the current legal system ,we can analogical apply the rule of joint dangerous act ,and correct the causal relationship to resolve such incidents. It will be more fair and just .

Objective To explore the feasibility of establishing a tree shrew model of chronic gastrointestinal mucosal injury. Methods A total of 12 adult male tree shrews were randomly divided into 3 groups. The experimental groups 1 and 2 were administered with intraperitoneal injection of 2 mg/(kg·d)and 1 mg/(kg·d)of 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine(MPTP)once every day for 56 days, respectively. The control group was given the same volume of sterile saline at the corresponding time points. Changes in the body weight of the tree shrews were observed. The contents of dopamine in the cerebrospinal fluid were detected. Gastrointestinal morphology was observed by stereoscope and histopathological changes of the gastrointestinal mucosa were examined by HE staining. Results The body weight and the contents of dopamine in the cerebrospinal fluid of the tree shrews in the model group were significantly decreased(P< 0.05 for both). Pathological changes to some extent of the gastric antrum, the gastric body and the duodenum were observed, without obvious differences between the 2 mg/kg group and the 1 mg/kg group. No obvious changes were found in the control group. Conclusions Long-term intraperitoneal injection with a low dose of MPTP is a feasible method for the establishment of a tree shrew model of chronic gastrointestinal mucosal injury. The optimal dose is 2 mg/(kg·d)every day for 56 days.

Objective To establish a safe and effective method of rhesus monkey biopsy to take liver and kidney samples under B-mode ultrasound guidance. Methods A total of 4 adult monkeys(weight:8-12 kg; sex: male; age:11 -12 years old)were anaesthetized with 5 -10 mg/kg of ketamine hydrochloride for each through intramuscular injection. After successful anesthesia, abdominal shaving and iodophor disinfection, they were monitored from intercostal area of right upper quadrant or lateral waist subcostal abdomen portions to find liver or kidney organ by MyLab 30CV B-mode ultrasonography with 3.5 Hz transducer which was fixed with a guiding frame. Large vessels such as the portal vein and inferior vena cava were carefully avoided. The range of the biopsy gun was set to 15 mm. When the puncture target and the puncture needle were positioned in the guide line, the puncture target was perpendicular to the puncture needle, and then the trigger button of the puncture needle was pressed to obtain the liver or kidney tissue samples respectively. After puncture,the needle was pulled out quickly. The obtained liver and kidney tissues were used to extract RNA. Results About 13 mg of liver or kidney tissue was obtained by each puncture with volume convertion. This method was fast,reliable and safe,and the total RNA had high purity and integrity. There was no postoperative bleeding and infection. Conclusions This is a very important method for obtaining liver and kidney tissue samples of rhesus monkeys with the guidance of ultrasound. With this method, the research cost can be reduced, the life quality and animal welfare of laboratory non-human primates can be improved,and the accuracy of experimental result can be ensured.

Objective To provide reference values for bone mineral density(BMD)in different skeletal regions of female Wistar rats at different ages. Methods Thirty SPF female Wistar rats were selected. The BMD of different skeletal regions(skull,upper limbs,thighs,trunk,ribs,pelvis,spine and the whole body)was measured by dual energy X-ray absorptiometry(DXA)at 6,10,12,24 and 30 months of age. The bone mineral densities between different age groups and that of different skeletal regions in the same age groups were compared. Results The BMD of the skull,upper limbs,thighs,trunk,ribs,pelvis, spine and the whole body was increased rapidly with age, and reached a peak at 10 months of age. The BMD of the skull,upper limbs,thighs,trunk,ribs were significantly higher than the whole body BMD in the same month-age group(P< 0.05 or P< 0.01). However,there was no significant difference between the pelvic, spine and the whole body BMD(P> 0.05). There was a significant positive correlation among the three correlations(P<0.01). Conclusions Some background data are provided for the bone biology studies of female Wistar rats, and provide useful supplementary reference for the studies of bone metabolism in rats and their application in biomedicine.