Objective:To investigate the phenotypes of Rubinstein-Taybi syndrome (RSTS) caused by variants in the CREBBP or EP300 gene, and the correlation between genotype and phenotype.Methods:This case series study was performed on pediatric patients who were referred to the Children′s Hospital of Capital Institute of Pediatrics between January 2013 and July 2022. Both point variant and copy number deletion in CREBBP or EP300 gene were detected by whole exome sequencing, chromosomal microarray analysis, or copy number variation sequencing (CNV-seq). The variant categories were summarized and phenotype numbers were re-visited for RSTS patients. Based on variant types, the patients were divided into different groups (point variant or copy number deletion, EP300 or CREBBP point variant, and loss of function or missense variant). Phenotype counts between different groups were compared using the rank-sum test of two independent samples.Results:A total of 21 RSTS patients were recruited, including 12 males and 9 females, with ages ranging from 1 month to 14 years and 2 months. Among them, 67% (14/21) had point variants, and 33% (7/21) had copy number deletions. Out of these, 20 variants (95%) were de novo. Among 20 patients finishing phenotype count during re-visit, 95% (19/20) of the patients exhibited developmental delays before the age of 2 years. Additionally, 80% (16/20) of the patients had distinctive facial features. Considering phenotype count, no statistically significant difference was found between point variant (14 cases) and copy number deletion (6 cases) (5.0 (3.0, 7.0) vs. 5.0 (2.5, 5.3), Z=0.75, P=0.452), CREBBP (10 cases) and EP300 gene (4 cases) point variant (5.0 (3.8, 7.0) vs. 4.0 (2.0, 6.0), Z=1.14, P=0.253), and loss of function (9 cases) and missense (5 cases) variant (6.0 (4.5, 7.0) vs. 3.0 (2.5, 5.5), Z=1.54, P=0.121). Conclusions:Patients with RSTS primarily exhibit developmental delays in early childhood. Specific facial features serve as suggested signs of genetic testing. However, no significant genotype-phenotype correlation is found.

IgA nephropathy is a common primary glomerular disease,and autophagy plays an important role in maintaining the homeostasis of the internal environment.Dysfunction of cellular autophagy can affect the occurrence and development of IgA nephropathy.This article focused on the molecular mechanism of TCM regulating autophagy in renal intrinsic cells,and found that TCM extracts and formulas mainly regulate autophagy through PI3K/Akt/mTOR,TLR4/NF-κB,MAPK,Nrf2/HO-1,NLRP3 and other signaling pathways.Furthermore,it could intervene in pathological damage such as renal fibrosis,inflammation,and oxidative stress,delaying the progression of IgA nephropathy,in order to provide reference for the clinical treatment and new drug development of IgA nephropathy.

Diabetic kidney disease is one of the complications of diabetes,which can progress to end-stage renal disease.In recent years,it has been found that miRNAs have become a research hotspot,with miRNA-21 regulating transforming growth factor β1(TGF-β1)/Smads,phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT),Wnt/β-catenin and other signaling pathways to promote the progress of diabetic kidney disease.Studies have showed that traditional Chinese medicine has a regulatory effect on the expression of miRNA-21 and can target miRNA-21 to regulate TGF-β1/Smads,phosphatase and tensin homolog/PI3K/AKT/mammalian target of rapamycin(mTOR),peroxisome proliferator activated receptors and other signal transduction pathways to trigger signal cascade reactions,which intervene in pathological processes such as fibrosis,inflammation,oxidative stress and autophagy.In this article,the role of miRNA-21 in diabetic kidney disease and the intervention of traditional Chinese medicine were summarized,in order to provide some reference for the treatment of diabetic kidney disease and the development of new drugs.

OBJECTIVE: To analyze the clinical characteristics and spectrum of SPTB gene variants among 16 Chinese children with Hereditary spherocytosis (HS) and explore their genotype-phenotype correlation. METHODS: Sixteen children who were diagnosed with HS at the Affiliated Hospital of Capital Institute of Pediatrics from November 2018 to July 2022 were selected as the research subjects. Genetic testing was carried out by whole exome sequencing. Candidate variants were verified by Sanger sequencing and subjected to bioinformatic analysis and prediction of 3D structure of the protein. Correlation between the SPTB genotypes and clinical phenotypes was analyzed using Chi-squared test. RESULTS: The male-to-female ratio of the HS patients was 6 : 10, with the median age being 7-year-and-10-month. Clinical features of the patients have included anemia, reticulocytosis and gradual onset of splenomegaly. Mild, moderate and severe anemia have respectively occurred in 56.25% (9/16), 31.25% (5/16) and 12.50% (2/16) of the patients. SPTB gene variants were detected in all patients, among which 10 were unreported previously and 7 were de novo in origin. Loss of function (LOF) variants accounted for 93.75% (15/16). Only one missense variant was detected. Eleven, 4 and 1 of the variants had occurred in the repeat domain, CH1 domain, and dimerization domain, respectively. There was no significant correlation between the type or domain of the SPTB gene variants with the clinical features such as severity of anemia (x² = 3.345, P > 0.05). All of the variants were predicted to be pathogenic or likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics. CONCLUSION Mild to moderate anemia are predominant clinical features of the HS children harboring a SPTB gene variant, for which LOF variants are the main mutational type. The clinical feature of HS is unaffected by the type of the variants.
Child ; Female ; Humans ; Male ; Computational Biology ; Genetic Testing ; Genomics ; Genotype ; Spherocytosis, Hereditary/genetics* ; East Asian People/genetics* ; Spectrin/genetics*

Copy number variants (CNVs) are common causes of human genetic diseases. CNVs detection has become a routine component of genetic testing, especially for pediatric neurodevelopmental disorders, multiple congenital abnormalities, prenatal evaluation of fetuses with structural anomalies detected by ultrasound. Although the technologies for CNVs detection are continuously improving, the interpretation is still challenging, with significant discordance across different laboratories. In 2020, the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) developed a guideline for the interpreting and reporting of constitutional copy number variants, which introduced a quantitative, evidence-based scoring framework. Here, we detailed the key points of interpreting the copy number gain based on the guideline, used six examples of different categories to illuminate the scoring process and principles. We encourage a professional understanding and application of this guideline for the detected copy number gains in China in order to further improve the clinical evaluation accuracy and consistency across different laboratories.
Child ; DNA Copy Number Variations ; Female ; Genetic Testing ; Genetics, Medical ; Genome, Human/genetics* ; Genomics ; Humans ; Pregnancy ; United States

Objective:To observe the efficacy of dexamethasone intravitreal implant (DEX) combined with pars plana vitrectomy (PPV) in eyes with severe idiopathic epimacular membrane (IMEM).Methods:A prospective clinical case study. From December 2018 to May 2021, 24 patients with 25 eyes of severe IMEM diagnosed in Tianjin Medical University Eye Hospital were included in the study. Among them, 7 males had 7 eyes, 17 females had 18 eyes. Age was 57 to 84 years old. The IMEM stage was 3 to 4 examined by spectral domain optical coherence tomography (SD-OCT). All eyes were performed best corrected visual acuity (BCVA) and central macular thickness (CMT) by SD-OCT. The patients were randomly divided into PPV group (11 eyes) and PPV+DEX group (14 eyes). Standard PPV by three-channel 25G was performed. Phacoemulsification, membrane stripping and intraocular lens implantation were combined during the operation. Patients received vitreous injection of 0.7 mg DEX in PPV+DEX group at the end of the operation. At 1 week, 1 month, 3 months and 6 months after operation, the same equipments and methods were used to perform relevant examinations. The changes of BCVA and CMT were compared between the two groups by t test. Results:Compared with before operation, at 1, 3 and 6 months after operation, the BCVA of the eyes in the PPV+DEX group was significantly improved ( t=3.974, 4.639, 4.453), CMT was significantly decreased ( t=2.955, 3.722, 4.364), the differences were statistically significant ( P<0.05); at 3 and 6 months after surgery, the BCVA of the eyes in the PPV group was significantly improved ( t=2.983, 4.436), CMT was significantly decreased ( t=2.983, 3.461), the differences were statistically significant ( P<0.05). Conclusion:In the treatment of severe IMEM, DEX can accelerate the early postoperative visual recovery and reduce CMT.

Cervical cancer is a common malignant tumor of female reproductive system. The treatment of cervical cancer is based on surgery and radiotherapy (or concurrent chemoradiation). Lower extremity lymphedema (LEL) is a frequent complication after cervical cancer treatment, which significantly affects the quality of life of patients. Both pelvic surgery and radiation for cervical cancer can lead to LEL. The risk factors for LEL are complicated and involving characteristics regarding patient (age, comorbidities, lifestyle, etc.), tumor [International Federation of gynecology and Obstetrics (FIGO) stage, lymph node metastasis, etc.], and treatment (number of resected lymph nodes, removal of circumflex iliac nodes, adjuvant therapy, etc.). Comprehensive measures are proposed to prevent cervical cancer patients from LEL, and further investigations in terms of effectiveness are warranted.

Objective To understand phthalic acid esters pollution of daily consumed food in Guangzhou City，and evaluate the hazard of phthalic acid esters exposure in residents dietary. Methods Detected the content of phthalic acid esters in 10 types of food by gas chromatography-mass spectroscopy（GC-MS）methods .It combined with a survey on dietary nutrients intake of Guangzhou residents was conducted．Hazard index on the dietary exposure assessment of chemicals in food was applied. Results It showed that the highest levels of DBP，DEHP and DIBP，from the mixed diet samples in Guangzhou were 1.256，1.418，0.576 mg/kg respectively；and the exposure level of DBP，DEHP and DIBP were 2.431、5.981、2.408μg/kg.d ;HQ was respectively 0.243、0.125、0.025. HI was 0.393. Conclusion The dietary contamination of phthalic acid esters for Guangzhou was kept at a low level.But the pollution of 3 kinds of mixed samples such as meats，eggs，aquatic and products may be a certain risk of health that should attract more attention.

Objective:To observe the functional changes of skeletal muscle in severely burned rats, and to investigate the effects and possible mechanisms of Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway inhibitor in skeletal muscle function.Methods:The experiment research method was applied. One hundred and twenty male Wistar rats of 8-week-old were divided into sham injury group, simple burn group, and burn+JAK/STAT3 inhibitor group according to the random number table, with 40 rats in each group. Rats in simple burn group and burn+JAK/STAT3 inhibitor group were inflicted with 50% total body surface area full-thickness scald on the back and abdomen, and rats in sham injury group were sham injured. Rats in burn+JAK/STAT3 inhibitor group were intraperitoneally injected with JAK/STAT3 inhibitor ruxolitinib. On post injury day (PID) 0 (immediately), 1, 4, 7, and 14, 8 rats in each group were used to measure the specific force generated by extensor digitorum longus in optimal length stimulated with pulse frequency of 20, 40, 60, 80, 100, 120, 140, and 160 Hz using a multichannel electrophysiological instrument, and specific force in fatigue period of extensor digitorum longus in optimal length stimulated with pulse frequency of 50 Hz for 0, 10, 20, 30, 60, 120, 180, 240, and 300 s. On PID 0, 1, 4, 7, and 14, carbonyl compound content of extensor digitorum longus was determined by ultraviolet spectrophotometry, and ATP content of extensor digitorum longus was determined by micrometry. Data were statistically analyzed with analysis of variance for repeated measurement, analysis of variance for factorial design, Bonferroni method, and t test. Results:Compared with those of sham injury group, specific forces of extensor digitorum longus of rats in simple burn group were significantly decreased after being stimulated with all the pulse frequency on PID 0, 1, 7, and all the pulse frequency except for 20 Hz on PID 4, and pulse frequency of 20 and 40 Hz on PID 14 ( P<0.05 or P<0.01). Compared with those of simple burn group, specific forces of extensor digitorum longus of rats in burn+JAK/STAT3 inhibitor group were significantly increased after being stimulated with all the pulse frequency except for 20 Hz on PID 1 and all the pulse frequency on PID 4, 7, and 14 ( P<0.05 or P<0.01). Compared with those of sham injury group, specific forces of extensor digitorum longus of rats in simple burn group were significantly decreased in fatigue period at all the time points post injury and stimulation time points except for 240 s on PID 7 ( P<0.05 or P<0.01). Compared with those of simple burn group, specific forces of extensor digitorum longus of rats in burn+JAK/STAT3 inhibitor group were obviously increased in fatigue period at all the stimulation time points except for 60 and 300 s on PID 1 and 240 s on PID 4, and all the stimulation time points on PID 7 and 14 ( P<0.05 or P<0.01). The carbonyl compound content of extensor digitorum longus of rats in simple burn group on PID 0, 1, 4, 7, and 14 was (0.651±0.155), (0.739±0.194), (0.618±0.086), (0.813±0.162), (0.615±0.115) nmol/mg, which were obviously higher than (0.196±0.019), (0.156±0.004), (0.169±0.023) (0.156±0.027), (0.175±0.008) nmol/mg in sham injury group ( t=7.219, 6.491, 10.938, 9.182, 11.589, P<0.01) and (0.538±0.069), (0.369±0.059), (0.273±0.061), (0.334±0.109), (0.318±0.101) nmol/mg in burn+JAK/STAT3 inhibitor group ( t=2.446, 4.689, 8.355, 5.754, 6.097, P<0.05 or P<0.01). The ATP content in extensor digitorum longus of rats in simple burn group on PID 1, 4, 7, and 14 was obviously lower than that in sham injury group ( t=7.159, 7.591, 7.473, 4.026, P<0.01) and burn+JAK/STAT3 inhibitor group ( t=2.295, 2.575, 2.453, 2.997, P<0.05). Conclusions:After severe burn, the specific force of extensor digitorum longus in rats decreased significantly after being stimulated with different pulse frequencies, and the extensor digitorum longus in rats was prone to fatigue. Blocking the JAK/STAT3 signaling pathway can reduce the oxidative stress of muscle protein and increase ATP content, thereby reducing the muscle strength decline caused by burn injury and improving the muscle strength decline during fatigue period.

Objective: To explore the effects of insulin therapy on skeletal muscle wasting (SMW) in severely scalded rats and its related mechanism. Methods: Totally 48 male Wistar rats aged 7-8 weeks were divided into simple scald (SS) group and insulin therapy (IT) group according to the random number table, with 24 rats in each group. After weighing the body mass and measuring the blood glycemic level of the tail end with a glucometer, the rats in the two groups were immersed in hot water at 94 ℃ for 12 seconds to make a full-thickness dorsal scald model involving 30% total body surface area. Rats in group IT were subcutaneously injected with 1 U/kg insulin glargine at 8: 00 a day from post injury day (PID) 1 to 7, whilst rats in group SS were given the same amount of normal saline. Rats in the two groups were given 10 mL/kg enteral nutritional emulsion by intragastric infusion at 8: 00 (after insulin administration), 13: 00, and 18: 00 a day respectively from PID 1 to 7. The blood glycemic levels of tail end of rats in the two groups were measured by glucometer before insulin administration on PID 1-4, 6, and 7 and on every morning of PID 8, 9, 11, 12, and 14. The body mass of rats in the two groups on PID 14 without any treatment was weighed. Eight rats from each group were collected respectively on PID 4, 7, and 14 to harvest tibialis anterior muscle (TAM) samples. The mass of TAM on PID 14 was weighed. The ultrastructural changes of TAM myocytes on PID 7 were observed with transmission electron microscope. The apoptotic rates of TAM myocytes on PID 4, 7, and 14 were assessed by the assay of terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphate-biotin nick end labeling, the expressions of cysteine-aspartic protease-3 (caspase-3) of TAM on PID 4, 7, and 14 were detected with immunohistochemistry, and protein expressions of endoplasmic reticulum (ER) stress (ERS) associated proteins glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein-homologous protein (CHOP), and activated caspase-12 of TAM on PID 4, 7, and 14 were detected with Western blotting. Data were processed with completely random design t test, analysis of variance for repeated measurement, analysis of variance for factorial design, t test, and Bonferroni correction. Results: The blood glycemic level and body mass of rats in the two groups before injury were similar (t=0.204, 0.405, P>0.05). There were no statistically significant differences in blood glycemic levels of rats between the two groups on PID 1, 6, 9, 11, 12, and 14 (t=0.229, 3.339, 1.610, 0.178, 0.181, 0.079, P>0.05). Compared with those of group SS, blood glycemic levels of rats in group IT were significantly lower on PID 2, 3, 4, 7, and 8 (t=7.245, 4.165, 4.609, 4.018, 3.995, P<0.05 or P<0.01). On PID 14, the body mass and TAM mass of rats in group IT were (271±19) g and (0.47±0.05) g respectively, both obviously higher than (254±12) g and (0.43±0.04) g of group SS (t=2.159, 2.375, P<0.05). On PID 7, nuclear pyknosis and deformation, chromosome misdistribution, and ER swelling in TAM myocytes of rats in group SS were observed; the apoptotic alterations and ER swelling of TAM myocytes were alleviated in rats of group IT as compared with those of group SS. The apoptotic rates of TAM myocytes of rats in group IT were obviously lower than those of group SS on PID 4, 7, and 14 (t=4.262, 9.153, 9.799, P<0.01). The expressions of caspase-3 in TAM of rats in group IT were obviously lower than those of group SS on PID 7 and 14 (t=10.429, 7.617, P<0.01). Compared with those of group SS, the protein expressions of GRP78 were obviously increased on PID 4 and 14 (t=4.172, 4.437, P<0.05), the protein expressions of activated caspase-12 were obviously decreased on PID 7 and 14 (t=11.049, 11.181, P<0.01), and the protein expressions of CHOP were obviously decreased on PID 4, 7, and 14 (t=13.837, 9.572, 6.930, P<0.01) in TAM of rats in group IT. Conclusions Insulin therapy may reduce skeletal muscle myocytes apoptosis and SMW by alleviating ERS in rats with severe scald.