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With the improvement of DNA methylation detection techniques, studies on age-related methylation sites have found more age-specific ones across tissues, which improves the sensitivity and accuracy of age estimation. In addition, the establishment of various statistical models also provides a new direction for the age estimation of tissues from different sources. This review summarizes the related studies of age estimation based on DNA methylation from the aspects of detection technology, age-related cytosine phosphate guanine site and model selection in recent years.
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DNA Methylation , Forensic Genetics/methods , CpG Islands , Forensic MedicineABSTRACT
This article reports a case of nevus trichilemmocysticus. The patient, a 48-year-old man, presented with multiple filiform keratoses and nodules. Physical examination identified multiple subcutaneous papules and nodules on the scalp, filiform keratoses on the face and bilateral ears, in addition to linear blackheads on trunk and limbs. The patient also exhibited hair loss and hypoplastic tooth. Histopathology revealed trichilemmal cyst. Nevus trichilemmocysticus is a rare organoid nevus. We reviewed literature in order to raise the awareness of the syndrome.
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This study aimed to prepare silk fibroin nanoparticles (SF-NPs) and assess the physicochemical properties and biocompatibility of the formulation. An optimized and simplified solvent displacement method was employed to obtain SF-NPs. Single-factor prescription screening, such as silk fibroin (SF) solution concentration, the ratio of SF solution to organic solvent, ultrasonication power and time, and different types of organic phases, was used to optimize the formulation. The characterization of the optimal formulation included particle size, polydispersity index (PDI), zeta potential, morphology, and stability. The in vitro cell compatibility of the nanoparticles was evaluated using CCK-8 and Calcein-AM/PI cell viability staining. The results showed that when SF concentration was 20 mg·mL-1, volume ratio of aqueous phase to acetone was 1∶6, ultrasonic power was 80 W and ultrasonic time was 3 min, the best SF-NPs was obtained. The nanoparticles prepared in this study exhibit a near-spherical shape, with a uniform size distribution, having an average size of 144.8 nm, a PDI of 0.174, and a zeta potential of -27.35 mV. Results from in vitro cell experiments demonstrate excellent cell compatibility of SF-NPs, showing the ability to promote cell proliferation. The SF-NPs which were successfully prepared in this study exhibit uniform particle size and excellent biocompatibility.
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To investigate the effects and mechanism of the combination of Morus alba L. (Sangzhi) alkaloids(SZ-A) and metformin (Met) on glucose metabolism in type 2 diabetic mice, KKAy mice were divided into four groups according to the glucose and lipid indexes: control group (control), Morus alba L. (Sangzhi) alkaloids group (SZ-A, 100 mg·kg-1), metformin group (Met, 100 mg·kg-1) and combined administration group (combination, Comb, 100 mg·kg-1 SZ-A + 100 mg·kg-1 Met). All groups were administered by gavage once daily for 7 weeks accompanied with monitoring food intake, water intake, body weight as well as glycemia. Additionally, oral glucose tolerance test (OGTT), insulin tolerance test (ITT) and oral sodium pyruvate tolerance test (OPTT) were performed at week 2, week 5, week 6, respectively. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (00004332). We determined the weight and lipid content of liver, and then performed the histopathological analysis after sacrificed. Furthermore, Western blot assay was used to detect the protein levels of key molecules of PI3K/PDK1/Akt/GLUT signaling pathway in liver, muscle and adipose tissue. Compared to the SZ-A or Met monotherapy group, SZ-A + Met significantly improved the glucose metabolism disorder, which was showed in reduced food intake, water intake, the level of fasting blood glucose, postprandial blood glucose and glycosylated hemoglobin A1c (HbA1c) of KKAy mice, as well as improved glucose tolerance, enhanced insulin sensitivity and inhibited gluconeogenesis. In addition, SZ-A + Met obviously up-regulated the protein expression levels in PI3K/PDK1/Akt/GLUT signaling pathway in liver, muscle and adipose tissue of KKAy mice. Moreover, the liver lipid accumulation and blood aminotransferase level of KKAy mice in the combined administration group were significantly reduced. Therefore, we concluded that the combination of SZ-A and Met improved glucose metabolism and inhibited the occurrence and development of T2DM via promoting glucose uptake and utilization, suggesting that the combination of SZ-A and Met is a more useful treatment for T2DM.
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Ramulus Mori (Sangzhi) alkaloids (SZ-A) are a group of polyhydroxy alkaloids extracted and isolated from the traditional Chinese medicine mulberry twig, which is mainly used for the treatment of type 2 diabetes mellitus (T2DM). In addition to acting as a glycosidase inhibitor in the small intestine after oral administration, SZ-A can also be absorbed into blood and widely distributed to target organs related to diabetes, exerting multiple pharmacological effects. It is important to elucidate the possible pharmacokinetic influences of SZ-A for its clinical rational applications, such as drug interactions, the effects of food and alcohol on the absorption of SZ-A. However, studies in this area are limited. Therefore, the pharmacokinetic interactions between orally administrated SZ-A (50 mg·kg-1) and metformin hydrochloride (Met, 200 mg·kg-1) in Sprague-Dawley (SD) rats were examined. Then, the effect of food (standard feed) on the pharmacokinetics of SZ-A was investigated using fasting administration of SZ-A (50 mg·kg-1) in rats as a control. Finally, we investigated the pharmacokinetic characteristics of SZ-A (50 mg·kg-1) in different concentrations alcohol solutions using aqueous solution of SZ-A administered to rats as a control to evaluate the effect of alcohol on the bioabsorption of SZ-A. The results showed no significant pharmacokinetic interactions between SZ-A and Met after combination treatment. The standard feed had little effect on the pharmacokinetic profile of SZ-A. Alcohol retarded the absorption of SZ-A, resulting in a significant decrease in the Cmax of SZ-A. The decrease was greater at higher alcohol concentrations; however, no significant difference was observed in the AUC0-t. These results support the clinical rational applications of SZ-A. All animal protocols were approved by the Ethics Committee of Kangtai Medical Laboratory Service Hebei Co., Ltd. (Hebei, China) (No. MDL2022-01-17-1).
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Objective:To evaluate the correlation between inflammatory diet and reflux esophagitis (RE) with the dietary inflammatory index (DII), and to provide scientific evidence for the prevention and treatment of RE at the level of dietary guidance.Methods:From December 2021 to September 2022, 145 RE patients (RE group) who visited the First Affiliated Hospital of Xinjiang Medical University were recruited. During the same period, 145 subjects who underwent check-ups at the First Affiliated Hospital of Xinjiang Medical University were selected as the healthy control group, and age and gender were matched according to the ratio of 1 to 1. The baseline data of the 2 groups, including body mass index, the history of smoking and drinking, poor dietary habits, and physical activity intensity were collected. Dietary intake of the patients was assessed by a semi-quantitative food frequency questionnaire, and the overall DII was calculated to evaluate the potential anti-inflammatory or pro-inflammatory effects of diet. According to the tertiles of the DII of the healthy control group (33.3% and 66.7% as the cut-off), dietary inflammatory potential was divided into low (<-0.06), moderate (-0.06 to 1.11) and high pro-inflammatory potential diet (>1.11). Logistic regression model was performed to analyze the correlation between DII and RE risk. Linear trend test was used to compare the overall change trend of RE risk OR value along with the increase of DII. Independent sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:The body mass index of RE group was higher than that of healthy control group( (24.11±2.57) kg/m 2 vs. (23.38 ±2.60) kg/m 2), and the difference was statistically significant ( t=-2.41, P=0.017). The proportions of smoking, drinking, over-eating, and eating within 3 h before bedtime of RE group was higher than those of the healthy control group (42.8%, 62/145 vs. 31.0%, 45/145; 31.0%, 45/145 vs. 16.6%, 24/145; 33.1%, 48/145 vs. 17.9%, 26/145; 52.4%, 76/145 vs. 13.1%, 19/145), and the differences were statistically significant ( χ2=4.28, 8.39, 8.78 and 50.86, P=0.039, 0.004, 0.003 and<0.001). While the proportions of night snacking and moderate to severe physical activity of RE group were lower than those of the healthy control group (14.5%, 21/145 vs. 24.1%, 35/145; 22.8%, 33/145 vs.37.2%, 54/145), and the differences were statistically significant ( χ2=4.34 and 7.24, P=0.037 and 0.007). The DII of RE group was higher than that of the healthy control group (1.05 (0.03, 1.62) vs. 0.34(-0.61, 1.35)), and the difference was statistically significant ( Z=8 661.50, P=0.010). Compared with the low pro-inflammatory potential diet, high pro-inflammatory potential diet had a 1.30-fold increased the risk of RE ( OR=2.30, 95% confidence interval (95% CI) 1.29 to 4.09, P=0.005). After adjusting for total energy intake, age, gender, ethnicity, body mass index, education level, and physical activity intensity, the high pro-inflammatory potential diet was still positively correlated with the risk of RE ( OR=2.58, 95% CI 1.16 to 5.76, P=0.020). In the continuous DII, the risk of RE increased by 36% for each 1 increase in DII ( OR=1.36, 95% CI 1.11 to 1.68, P=0.003). After adjusting for major confounding factors, the continuous DII was still positively correlated with the risk of RE ( OR=1.41, 95% CI 1.08 to 1.85, P=0.012; OR=1.42, 95% CI 1.05 to 1.93, P=0.023). The results of trend test showed that the higher the DII, the greater the risk of RE ( P=0.039). Conclusions:Pro-inflammatory diet is correlated with the increased risk of RE, and there is a certain dose-response relationship. Reasonable reduction of the intake of pro-inflammatory food may be beneficial to reduce the risk of RE.
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Objective:To analyze 141 cases clinically misdiagnosed as melanoma, and to improve the understanding and diagnosis of diseases.Methods:Totally, 141 cases preliminarily diagnosed as melanoma, which was finally excluded according to histopathological examination results, were collected from the pathological database of Department of Dermatology, Xijing Hospital, The Fourth Military Medical University from November 2001 to September 2019, and their clinical and histopathological data were analyzed retrospectively.Results:Among the 141 cases clinically misdiagnosed as melanoma, 64 were males and 77 were females. Their median age at the time of misdiagnosis was 51 years, and the average disease duration was 103.4 months. The patients mainly presented with patches and papules, most of which were black in color. Based on histopathological manifestations, 35 patients were diagnosed with pigmented nevi, 29 with basal cell carcinoma, 15 with seborrheic keratosis, 7 with Bowen′s disease, 6 with nail melanin spots, 5 with epidermal cysts, 4 with poroma, 4 with hemorrhage, 4 with dermatofibroma, and 23 with other skin diseases.Conclusions:In clinical practice, some diseases with characteristics of melanoma are liable to be misdiagnosed. It is necessary to grasp their clinical features and actively carry out auxiliary examinations such as dermoscopy and histopathological examinations to confirm the diagnosis and reduce the misdiagnosis rate.
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In this study, alkali-soluble polysaccharide was extracted from Poria residue, and the structure of alkali-soluble polysaccharide was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), and differential scanning calorimetry (DSC). The physical morphology of alkali-soluble polysaccharide and ethyl cellulose (EC) was investigated by scanning electron microscopy (SEM), and the focus on angle of repose, bulk density, tapped density, Carr index, interparticle porosity, cohesion index, Hausner ratio, etc. The physical fingerprints were drawn, and the powder properties were evaluated by multivariate analysis. Diclofenac sodium extended-release tablets were prepared by direct compression method using alkali-soluble polysaccharide and EC as insoluble backbone materials to evaluate the basic properties of the extended-release tablets, investigate the in vitro drug release behavior and study the release mechanism. The results showed that alkali-soluble polysaccharide is a semi-crystalline polymer with smooth lamellar structure, and its stacking and compressibility are stronger than EC. The in vitro release experiments showed that the slow release performance of alkali-soluble polysaccharide is stronger than EC, and the release behavior of the prepared slow release tablets is in accordance with the Higuchi model. The pore structure is formed inside the tablets during the release process, and the release mode is pore diffusion release. The results of this study are of great significance for the development of new slow-release materials and the rational use of resources.
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AIM: To investigate the effect of the expression of miR-375 on the proliferation and invasion of choroidal melanoma(CM)MUM-2B cells.METHODS: MUM-2B cells were cultured and were transfected with miR-375 mimic sequence(mimic group), miR-375 inhibitor sequence(inhibitor group), negative control group and no treatment(blank group). The qRT-PCR, CCK-8, apoptosis and Transwell experiments were used respectively to detect the expression of miR-375, cell proliferation activity, apoptosis, cell migration and invasion.RESULTS: Compared with the negative control group(1.01±0.10)and the blank group(1.03±0.07), the expression level of miR-375 in the cells of the mimic group(2.65±0.15)was increased, while the expression level of miR-375 in the cells of the inhibitor group(0.28±0.06)was decreased(P<0.05). Compared with the blank group and negative control group, the OD values of the cells in the mimic group at 24, 48, 72, and 96h were decreased(P<0.05), while the OD values of the cells in the inhibitor group at 24, 48, 72, and 96h were increased(P<0.05). Compared with the apoptosis rates in the blank group and negative control group, which were(20.54±4.01)% and(22.80±4.28)%, the apoptosis rate in the mimic group(39.11±3.37)% was increased(P<0.05), while it was decreased in the inhibitor group(10.13±2.17)%(P<0.05). Compared with the blank group and negative control group, the number of migration cell and the number of invasion cell in the mimic group were decreased(P<0.05), while the number of migration cell and the number of invasion cell in the inhibitor group were increased(P<0.05). CONCLUSIONS: Up-regulating the expression of miR-375 in MUM-2B cells can reduce cell proliferation activity, accelerate cell apoptosis, and inhibit cell migration and invasion, while down-regulating the expression of miR-375 has the opposite effect. It indicates that miR-375 may play the function of tumor suppressor in the course of CM.
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ObjectiveTo explore the effect of Anmeidan on the sleep quality and serum levels of brain-derived neurotrophic factor （BDNF）， glial fibrillary acidic protein （GFAP）， and irisin in the patients with chronic insomnia. MethodA multicenter， randomized， double-blind， placebo-controlled clinical study was carried out， including 480 patients with chronic insomnia （deficiency syndrome） in Wuhan （Hubei）， Guangzhou （Guangdong）， and Lanzhou （Gansu）. They were randomized into an observation group and a control group at a ratio of 1∶1. The observation group was orally administered with Anmeidan granules at a dose of 11 g， 3 times per day， and the control group with Anmeidan simulant at a dose of 11 g， 3 times per day， Both groups of patients received sleep education after enrollment. After 4 weeks of medication， the Athens insomnia scale （AIS） scores， Spiegel scale scores， and serum levels of BDNF， GFAP， and irisin were compared between the two groups as well as between before and after treatment. ResultA total of 480 adult patients with chronic insomnia were enrolled in this study， with 64 patients falled off. Finally， the 415 patients were included in the analysis， including 213 patients in the observation group and 202 patients in the control group. There was no difference in age or sex between the two groups of patients. Compared with before treatment， the treatment in both groups decreased the AIS and Spiegel scores （P<0.01）. After treatment， the observation group had lower AIS and Spiegel scores than the control group （P<0.01）. The treatment in the observation group slightly lowered the level of BDNF， elevated the level of irisin （P<0.05）， and lowered the level of GFAP （P<0.05） in the serum. After treatment， the observation group showed higher level of irisin （P<0.05） and lower levels of BDNF and GFAP in the serum than the control group. ConclusionAnmeidan may improve the sleep quality of patients with chronic insomnia by elevating the irisin level and lowering the GFAP level in the serum.
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Objective:To study the clinical features, treatment, and prognostic features of Kaufman Oculocerebrofacial syndrome.Methods:The clinical characteristics of a newborn with Kaufman Oculocerebrofacial syndrome admitted to the neonatal unit of Guiyang Maternal and Child Health Care Hospital was reported. Using "Kaufman Oculocerebrofacial syndrome", "Blepharophimosis-ptosis-intellectual disability syndrome" and "UBE3B gene" as keywords, databases including CNKI, VIP database, Wanfang database, Chinese medical journals full-text database, PubMed, Web of Science database and Embase database were searched from the date of establishment to June 2022. The clinical characteristics, treatment and prognosis of Kaufman Oculocerebrofacial syndrome from published literature were summarized.Results:The proband was a boy presenting with small lid fissure, wide eye spacing and feeding difficulties. Whole exome sequencing revealed compound heterozygous mutation in the UBE3B gene, c.1445_1448dupTCAC inherited from his father and c.1703dupA inherited from his mother, both variants had not been reported in the domestic and foreign literature thus far. A total of 34 newborn cases were summarized from 11 case reports, including this report. The main clinical manifestations were developmental delay (35/35), peculiar facial features (35/35), narrow eye slits (35/35), feeding difficulties (33/35), ear abnormalities (33/35), hypotonia (32/35), mouth abnormalities (31/35), breathing difficulties (26/35), small jaws (25/35) and low birth weight (16/35).There is no effective treatment available, and a total of 4 cases followed up to over 16 years old have been reported, all of which have severe mental retardation, language deficiency, along with other serious neurological diseases.Conclusions:when children exhibit symptoms such as narrow eye fissures, feeding difficulties, hypotonia, developmental delays, and peculiar facial features in the neonatal period, whole exome sequence can be used to aid diagnosis and evaluate for Kaufman Oculocerebrofacial syndrome. Families with children of Kaufman Oculocerebrofacial syndrome may undergo prenatal diagnosis based on genetic findings.
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Objective:To study the clinical application of jejunal feeding tube (J-tube) for early enteral nutrition after surgical treatment of upper digestive tract malformation in newborns.Methods:From January 2019 to December 2021, newborns with upper digestive tract malformation received stage Ⅰ small bowel resection and anastomosis in our hospital were enrolled in this prospective randomized controlled study. According to different types of postoperative nutritional support, these patients were randomly assigned into J-tube group and control group using block randomization method. The J-tube group were given enteral nutrition vis J-tube within 48-72 h after surgery and the control group were given oral feeding after the recovery of gastrointestinal function. Calories and proteins intake, growth indicators, duration of hospital stay and parenteral nutrition, time needed for full oral feeding and complications were compared between the two groups.Results:A total of 24 patients were in J-tube group and 28 in controlled group. No significant differences existed on the general status between the two groups ( P>0.05). The average daily intake of calories and proteins in j-tube group in the first week after surgery were significantly higher than control group [(108.7±8.3) kcal/(kg·d) vs. (97.9±7.0) kcal/(kg·d), (3.4±0.3) g/(kg·d) vs. (3.1±0.2) g/(kg·d)] ( P<0.05). No significant differences existed in the average daily intake of calories and proteins during the second postoperative week between the two groups ( P>0.05). Compared with control group,J-tube group showed increased growth velocity in head circumference and weight over time ( P<0.05), while the trend over time in length growth was not significant ( P>0.05). No significant differences existed in the duration of hospital stay and parenteral nutrition, time needed for full oral feeding and complications between the two groups ( P>0.05). Conclusions:Enteral nutrition via J-tube 48-72 h after surgery is safe and feasible in the postoperative nutritional management of newborns with upper digestive tract malformation. This strategy may promote physical growth after surgery without increasing the incidences of complications.
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Objective:To assess the clinical effectiveness and safety of Omalizumab for treating pediatric allergic asthma in real world in China.Methods:The clinical data of children aged 6 to 11 years with allergic asthma who received Omalizumab treatment in 17 hospitals in China between July 6, 2018 and September 30, 2020 were retrospectively analyzed.Such information as the demographic characteristics, allergic history, family history, total immunoglobulin E (IgE) levels, specific IgE levels, skin prick test, exhaled nitric oxide (FeNO) levels, eosinophil (EOS) counts, and comorbidities at baseline were collected.Descriptive analysis of the Omalizumab treatment mode was made, and the difference in the first dose, injection frequency and course of treatment between the Omalizumab treatment mode and the mode recommended in the instruction was investigated.Global Evaluation of Treatment Effectiveness (GETE) analysis was made after Omalizumab treatment.The moderate-to-severe asthma exacerbation rate, inhaled corticosteroid (ICS) dose, lung functions were compared before and after Omalizumab treatment.Changes in the Childhood Asthma Control Test (C-ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) results from baseline to 4, 8, 12, 16, 24, and 52 weeks after Omalizumab treatment were studied.The commodity improvement was assessed.The adverse event (AE) and serious adverse event (SAE) were analyzed for the evaluation of Omalizumab treatment safety.The difference in the annual rate of moderate-to-severe asthma exacerbation and ICS reduction was investigated by using t test.The significance level was set to 0.05.Other parameters were all subject to descriptive analysis.A total of 200 allergic asthma patients were enrolled, including 75.5% ( n=151) males and 24.5% ( n=49) females.The patients aged (8.20±1.81) years. Results:The median total IgE level of the 200 patients was 513.5 (24.4-11 600.0) IU/mL.Their median treatment time with Omalizumab was 112 (1-666) days.Their first dose of Omalizumab was 300 (150-600) mg.Of the 200 cases, 114 cases (57.0%) followed the first Omalizumab dosage recommended in the instruction.After 4-6 months of Omalizumab treatment, 88.5% of the patients enrolled ( n=117) responded to Omalizumab.After 4 weeks of treatment with Omalizumab, asthma was well-controlled, with an increased C-ACT score [from (22.70±3.70) points to (18.90±3.74) points at baseline]. Four-six months after Omalizumab administration, the annual rate of moderate-to-severe asthma exacerbation had a reduction of (2.00±5.68) per patient year( t=4.702 5, P<0.001), the median ICS daily dose was lowered [0 (0-240) μg vs. 160 (50-4 000) μg at baseline] ( P<0.001), the PAQLQ score was improved [(154.90±8.57) points vs. (122.80±27.15) points at baseline], and the forced expiratory volume in one second % predicted (FEV 1%pred) was increased [(92.80±10.50)% vs. (89.70±18.17)% at baseline]. In patients with available evaluations for comorbidities, including allergic rhinitis, atopic dermatitis or eczema, urticaria, allergic conjunctivitis and sinusitis, 92.8%-100.0% showed improved symptoms.A total of 124 AE were reported in 58 (29.0%) of the 200 patients, and the annual incidence was 0(0-15.1) per patient year.In 53 patients who suffered AE, 44 patients (83.0%) and 9 patients (17.0%) reported mild and moderate AE, respectively.No severe AE were observed in patients.The annual incidence of SAE was 0(0-1.9) per patient year.Most common drug-related AE were abdominal pain (2 patients, 1.0%) and fever (2 patients, 1.0%). No patient withdrew Omalizumab due to AE. Conclusions:Omalizumab shows good effectiveness and safety for the treatment of asthma in children.It can reduce the moderate-to-severe asthma exacerbation rate, reduce the ICS dose, improve asthma control levels, and improve lung functions and quality of life of patients.
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OBJECTIVE To analyze the status quo of performance appraisal of pharmacy intravenous admixture services （PIVAS） in China based on literature analysis， and provide reference for the implementation of performance management of PIVAS in China. METHODS Retrieved from domestic and foreign databases such as CNKI， VIP， Wanfang， PubMed， Embase， the Cochrane Library and CBM， the literature on the status quo evaluation of performance appraisal of PIVAS in China was included from the inception to Sept. 2022. The descriptive analysis was carried out on performance appraisal measures， performance appraisal indicators， performance appraisal achievement， etc. RESULTS Twelve pieces of literature were included， involving 8 before-and-after controlled studies and 4 experience sharing. The performance appraisal subjects of 10 pieces of literature were all staff and those of 2 pieces of literature were nurses. The measures of PIVAS performance appraisal were roughly the same， mainly involving contents and indicators of workload， work quality （including errors）， clinical service satisfaction， labor discipline， department contribution， personal comprehensive evaluation， and so on， but the main accounting proportion was different. Performance appraisal indicators mainly included the rate of medical order review， dispensing rate， check rate， delivery rate， finished product review rate， etc. The performance appraisal achievement mainly included the improvement of work efficiency， the improvement of work quality， the reduction of error rate， and the improvement of clinical satisfaction and employee satisfaction. CONCLUSIONS By building performance appraisal system and adopting corresponding performance management measures of PIVAS， it can improve the work efficiency and quality， reduce the error rate， ensure the safety of patients’ medication， and promote the standardized management of PIVAS in China.
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OBJECTIVE@#To explore the clinical phenotypes and genetic diagnosis of 2 sporadic cases for cleidocranial dysplasia.@*METHODS@#The clinical data of two cases of CCD admitted to the Third Affiliated Hospital of Zhengzhou University on December 16, 2021 and December 9, 2021 were analyzed retrospectively, and the whole exome sequencing (WES), chromosome microarray analysis and copy number variation sequencing were performed.@*RESULTS@#The main ultrasonographic findings of the fetus had included poorly calcified skull bones, budging of parieto-occipital area, compression and deformation of skull, and loss of nasal bone. The infant's clinical phenotypes included delayed closure of anterior fontanelle, recurrent respiratory tract infection, growth retardation, and clavicular hypoplasia. By WES analysis, the fetus was found to harbor a heterozygous c.911_914delinsTTT variant of the RUNX2 gene, whilst the infant was found to harbor a heterozygous c.1008delT variant of the RUNX2 gene. Both variants were verified by Sanger sequencing to have occurred de novo.@*CONCLUSION@#For sporadic cases featuring cleidocranial dysplasia, prenatal ultrasonography is particularly important. Hypoplastic clavicle, skull calcification and nasal bone absence are the main features. Diagnosis should also be suspected for infants featuring growth retardation, recurrent respiratory tract infections and clavicular dysplasia. The identification of the c.911_914delinsTTT and c.1008delT variants of the RUNX2 gene has facilitated genetic counseling and prenatal diagnosis, and also expanded the mutational spectrum of the RUNX2 gene.
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Female , Humans , Pregnancy , Cleidocranial Dysplasia/genetics , Core Binding Factor Alpha 1 Subunit , DNA Copy Number Variations , Growth Disorders , Retrospective StudiesABSTRACT
OBJECTIVE@#To explore the prevalence and clinical manifestations of ring chromosomes among children featuring abnormal development.@*METHODS@#From January 2015 to August 2021, 7574 children referred for abnormal development were selected, and their peripheral blood samples were subjected to G-banded chromosomal karyotyping analysis.@*RESULTS@#Twelve cases of ring chromosomes were detected, which have yielded a prevalence of 0.16% and included 1 r(6), 2 r(9), 1 r(13), 1 r(14), 2 r(15), 1 r(21) and 3 r(X). The children had various clinical manifestations including growth and mental retardation, limb malformation, and congenital heart disease. For two children with r(9) and two with r(15) with similar breakpoints, one child with r(9) and one with r(15) only had growth retardation, whilst another with r(9) and another with r(15) also had peculiar facies and complex congenital heart disease. The r(X) has featured some manifestations of Turner syndrome.@*CONCLUSION@#Ring chromosomes are among the common causes for severe growth and mental retardation in children with diverse clinical phenotypes. Clinicians should pay attention to those with developmental anomalies and use chromosomal analysis to elucidate their genetic etiology.
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Humans , Ring Chromosomes , Intellectual Disability/genetics , Turner Syndrome/genetics , Phenotype , Heart Defects, Congenital/geneticsABSTRACT
OBJECTIVE@#To assess the application value of copy number variation sequencing (CNV-seq) for women with a high risk for fetal anomalies.@*METHODS@#Based on the results of non-invasive prenatal testing (NIPT), 271 high-risk pregnant women were divided into NIPT positive group (n = 83) and other anomaly group (advanced age, high risk by serological screening, repeated NIPT failure, adverse pregnancy history, abnormal ultrasound finding, and abnormal phenotype) (n = 188). CNV-seq was carried out to detect copy number variations (CNVs) in amniocytic DNA from the two groups of pregnant women, and karyotyping analysis of the amniotic cells was carried out for verification and comparison.@*RESULTS@#The amniocytes from 271 pregnant women were detected. The detection rate was 20.66% (56/271) for pathogenic CNVs by CNV-seq and 19.19% (52/271) for pathogenic karyotypes by karyotyping analysis. The difference was statistically significant (P < 0.05). CNV-seq had shown that, compared with NIPT positive group, the detection rates for likely pathogenic CNVs and variants of unknown significance (VUS) in other abnormality group were significantly higher [2.41%(2/83) vs. 5.32%(10/188)](P < 0.05).@*CONCLUSION@#CNV-seq can well suit the first-tier diagnosis for pregnant women suspected for fetal abnormality. In prenatal diagnosis settings, CNV-seq can identify additional and clinically significant cytogenetic abnormalities. In those with other abnormalities, the detection rates for likely pathogenic CNVs and VUS are higher than with the NIPT positive cases.
Subject(s)
Female , Pregnancy , Humans , DNA Copy Number Variations , Pregnancy, High-Risk , Prenatal Diagnosis/methods , Chromosome Aberrations , Chromosome Disorders/geneticsABSTRACT
In this study, the underlying mechanism of Qiwei Guibao Granules(QWGB) in the treatment of premature ovarian fai-lure(POF) was explored by the proteomics technique. Firstly, the POF model was induced in mice by intragastric administration of Tripterygium wilfordii glycosides solution at 50 mg·kg~(-1) for 14 days. Ten days prior to the end of the modeling, the estrous cycle of mice was observed every day to evaluate the success of modeling. From the 1st day after modeling, the POF model mice were treated with QWGB by gavage every day and the treatment lasted four weeks. On the 2nd day after the end of the experiment, blood was collected from the eyeballs and the serum was separated by centrifugation. The ovaries and uterus were collected and the adipose tissues were carefully stripped. The organ indexes of the ovaries and uterus of each group were calculated. The serum estrogen(E_2) level of mice in each group was detected by ELISA. Protein samples were extracted from ovarian tissues of mice, and the differential proteins before and after QWGB intervention and before and after modeling were analyzed by quantitative proteomics using tandem mass tags(TMT). As revealed by the analysis of differential proteins, QWGB could regulate 26 differentially expressed proteins related to the POF model induced by T. wilfordii glycosides, including S100A4, STAR, adrenodoxin oxidoreductase, XAF1, and PBXIP1. GO enrichment results showed that the 26 differential proteins were mainly enriched in biological processes and cellular components. The results of KEGG enrichment showed that those differential proteins were involved in signaling pathways such as completion and coalescence cascades, focal adhesion, arginine biosynthesis, and terpenoid backbone biosynthesis. The complement and coalescence cascades signaling pathway was presumably the target pathway of QWGB in the treatment of POF. In this study, the proteomics technique was used to screen the differential proteins of QWGB in the treatment of POF in mice induced by T. wilfordii glycosides, and they were mainly involved in immune regulation, apoptosis regulation, complement and coagulation cascade reactions, cholesterol metabolism, and steroid hormone production, which may be the main mechanisms of QWGB in the treatment of POF.
Subject(s)
Female , Humans , Mice , Animals , Primary Ovarian Insufficiency/chemically induced , Proteomics , Signal Transduction , Glycosides/adverse effectsABSTRACT
This study investigated the choroplast genome sequence of wild Atractylodes lancea from Yuexi in Anhui province by high-throughput sequencing, followed by characterization of the genome structure, which laid a foundation for the species identification, analysis of genetic diversity, and resource conservation of A. lancea. To be specific, the total genomic DNA was extracted from the leaves of A. lancea with the improved CTAB method. The chloroplast genome of A. lancea was sequenced by the high-throughput sequencing technology, followed by assembling by metaSPAdes and annotation by CPGAVAS2. Bioiformatics methods were employed for the analysis of simple sequence repeats(SSRs), inverted repeat(IR) border, codon bias, and phylogeny. The results showed that the whole chloroplast genome of A. lancea was 153 178 bp, with an 84 226 bp large single copy(LSC) and a 18 658 bp small single copy(SSC) separated by a pair of IRs(25 147 bp). The genome had the GC content of 37.7% and 124 genes: 87 protein-coding genes, 8 rRNA genes, and 29 tRNA genes. It had 26 287 codons and encoded 20 amino acids. Phylogenetic analysis showed that Atractylodes species clustered into one clade and that A. lancea had close genetic relationship with A. koreana. This study established a method for sequencing the chloroplast genome of A. lancea and enriched the genetic resources of Compositae. The findings are expected to lay a foundation for species identification, analysis of genetic diversity, and resource conservation of A. lancea.
Subject(s)
Phylogeny , Atractylodes/genetics , Genome, Chloroplast , Whole Genome Sequencing , Microsatellite Repeats , LamialesABSTRACT
OBJECTIVE@#To explore the clinical phenotype and genetic variants of a fetus with Glutaracidemia type II C (GA II C).@*METHODS@#Clinical data of a 32-year-old pregnant woman and her fetus with GA II C diagnosed at the Third Affiliated Hospital of Zhengzhou University in December 2021 due to the enlargement and enhanced echo of the kidneys and oligohydramnios fluid at 17 weeks were analyzed retrospectively. Amniotic fluid sample of the fetus and peripheral blood samples of the couple were collected for whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Copy number variation (CNV) was detected by using low-coverage whole genome sequencing (CNV-seq).@*RESULTS@#At 18 weeks' gestation, ultrasound revealed that the fetus had enlargement and enhanced echo of the kidneys along with no echo of renal parenchymal tubular fissure and oligohydramnios. MRI at 22 weeks' gestation confirmed that both kidneys were enlarged with uniformly increased abnormal T2 signal and decreased DWI signal. The volume of both lungs was small, with slightly higher T2 signal. No CNV was detected in the fetus. WES revealed that the fetus has harbored compound heterozygous variants of the ETFDH gene, namely c.1285+1G＞A and c.343_344delTC, which were inherited from its father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+PM2_Supporting+PS3_Supporting; PVS1+PM2_Supporting+PM3).@*CONCLUSION@#The c.1285+1G＞A and c.343_344delTC compound heterozygous variants of the ETFDH gene probably underlay the disease in this fetus. Type II C glutaric acidemia may manifest as bilateral kidney enlargement with enhanced echo and oligohydramnios. Discovery of the c.343_344delTC has enriched the spectrum of ETFDH gene variants.