Identification of genetic causes in children with unexplained epilepsy based on trio-whole exome sequencing.

Genotype and clinical phenotype analyses of 128 children were performed based on whole exome sequencing (WES), providing a reference for the provision of genetic counseling and the precise diagnosis and treatment of epilepsy. A total of 128 children with unexplained epilepsy were included in this study, and all their clinical data were analyzed. The children's treatments, epilepsy control, and neurodevelopmental levels were regularly followed up every 3 months. The genetic diagnostic yield of the 128 children with epilepsy is 50.8%, with an SNV diagnostic yield of 39.8% and a CNV diagnostic yield of 12.5%. Among the 128 children with epilepsy, 57.0% had onset of epilepsy in infancy, 25.8% have more than two clinical seizure forms, 62.5% require two or more anti-epileptic drug treatments, and 72.7% of the children have varying degrees of psychomotor development retardation. There are significant differences between ages of onset, neurodevelopmental levels and the presence of drug resistance in the genetic diagnostic yield (all p < 0.05). The 52 pathogenic/likely pathogenic SNVs involve 31 genes, with genes encoding ion channels having the largest number of mutations (30.8%). There were 16 cases of pathogenic/possibly pathogenic CNVs, among which the main proportions of CNVs were located in chromosome 15 and chromosome 16. Trio-WES is an essential tool for the genetic diagnosis of unexplained epilepsy, with a genetic diagnostic yield of up to 50.8%. Early genetic testing can provide an initiate appropriate therapies and accurate molecular diagnosis.

Inflammatory Studies of Dehydroandrographolide: Isolation, Spectroscopy, Biological Activity, and Theoretical Modeling.

Dehydroandrographolide (DA) was isolated and experimentally characterized utilizing FT-IR, UV-Vis, and NMR spectroscopy techniques along with detailed theoretical modelled at the DFT/B3LYP-D3BJ/6-311 + + G(d,p) level of theory. Substantially, molecular electronic property investigations in the gaseous phase alongside five different solvents (ethanol, methanol, water, acetonitrile and DMSO) were comprehensively reported and compared with the experimental results. The globally harmonized scale (GHS), which is used to identify and label chemicals, was also utilized to demonstrate that the lead compound predicted an LD50 of 1190 mg/kg. This finding implies that consumers can safely consume the lead molecule. Notable impacts on hepatotoxicity, cytotoxicity, mutagenicity, and carcinogenicity were likewise found to be minimal to nonexistent for the compound. Additionally, in order to account for the biological performance of the studied compound, in-silico molecular docking simulation analysis was examined against different anti-inflammatory target of enzymes (3PGH, 4COX, and 6COX). From the examination, it can be inferred that DA@3PGH, DA@4COX, and DA@6COX, respectively, showed significant negative binding affinities of -7.2 kcal/mol, -8.0 kcal/mol, and - 6.9 kcal/mol. Thus, the high mean binding affinity in contrast to conventional drugs further reinforces these results as an anti-inflammatory agent.

Recent advances in lamellar liquid crystal emulsification methods encapsulating natural active substances for functional cosmetics / 药学学报

Due to the high similarity with the lipid layer between human skin keratinocytes, functional cosmetics with layered liquid crystal structure prepared by liquid crystal emulsification technology encapsulating natural active substances have become a hot research topic in recent years. This type of functional cosmetic often has a fresh and natural skin feel, excellent skin barrier repair function and efficient moisturizing effect, etc., showing great potential in cosmetic application. However, the present research on the application of liquid crystal emulsification technology to functional cosmetics is still in the initial stage, and there are fewer relevant reports with reference values. Based on the mentioned above, this review provides a comprehensive summary of functional cosmetics with layered liquid crystal structures prepared by liquid crystal emulsification technology from the following aspects: the structure of human skin, the composition of lamellar liquid crystal, the advantages of liquid crystal emulsification technology containing natural active substances used in the field of functional cosmetics, the preparation process, main components, influencing factors during the preparation and the market functional cosmetics with lamellar liquid crystal structure. Finally, the prospect of the application of liquid crystal emulsification technology in functional cosmetics is presented, to provide useful references for those engaged in the research of liquid crystal emulsification technology-related functional cosmetics.

Effects of Lactobacillus Rhamnosus GG on Activated Microglia and Tau Phosphorylation in the Hippocampus of Aged Mice Induced by Anesthesia and Surgery / 中山大学学报(医学科学版)

ObjectiveTo investigate the effects of Lactobacillus rhamnosus GG （LGG）on microglia and Tau phosphorylation in the hippocampus of aged mice induced by anesthesia and surgery. MethodsA total of thirty 18-month-old C57BL/6J mice were randomly divided into three groups： control group， anesthesia surgery group， and anesthesia surgery + LGG group （10 mice/group）. The aged mice were oral administered by NS or LGG 109 CFU 150 μL once a day for 20 days. Then anesthesia surgery group and anesthesia surgery +LGG group received anesthesia with isoflurane and exploratory laparotomy. The activation status of microglia in the hippocampus was detected by immunofluorescence staining 12 hours after surgery. IL-6 concentration changes was detected by ELISA. The expression changes of Tau protein phosphorylation site （Tau-pS202/pT205） and total Tau protein was detected by western blot. ResultsThe microglia in the hippocampus of the control group were in a resting state， and the concentration of inflammatory factor IL-6 was （82.08 ± 12.07） pg/mL in control group. Compared to the control group， the anesthesia surgery group showed microglial cell Microglia were activated， the concentration of inflammatory factors IL-6 increased significantly to （123.7±5.72） pg/mL （P=0.000）， and the expression of phosphorylated Tau-pS202/pT205 increased the hippocampus （P=0.002）. Compared to the anesthesia surgery group， the activated microglia were inhibited， the concentration of IL-6 decreased to （96.68±9.59） pg/mL （P=0.008）， and the expression of phosphorylated Tau-pS202/pT205 reduced significantly in the AS+LGG group （P=0.002）. While there were no significant changes in total Tau protein among 3 groups. ConclusionPreoperative administration of probiotic LGG can alleviate the activation of microglia， increased secretion of inflammatory factors， and increased Tau protein phosphorylation levels in the hippocampus of elderly mice caused by anesthesia surgery.

Alteration of GABAergic neurons and abnormality of NKCC1/KCC2 in focal cortical dysplasia (FCD) type â ¡ lesions.

BACKGROUND: The current conclusions of molecular genetics still cannot satisfactorily explain the pathogenesis of focal cortical dysplasia (FCD) and the reason for drug resistance. The interneurons of GABA deserve attention. To observe the distribution and changes of GABAergic neurons and to explore the expression of cation chloride cotransporter NKCC1/KCC2 in focal cortical dysplasia (FCD) type II lesions is a highly significant job. METHODS: The expressions of GAD67(a marker of active GABAergic neuron), NKCC1 and KCC2 were detected by immunohistochemistry and immunohistochemistry double staining in 10 cases of FCD Ⅱa and 10 cases of FCD Ⅱb. The number of GAD67 positive neurons was counted, and the average absorbance (IA) of NKCC1 positive expression was measured, using Image Pro-Plus7.0 software. The data were statistically analyzed. RESULTS: The density of GABAergic neuron in focal dysplastic regions was significantly lower than that in the histologically "normal" cerebral cortex, regions from the same specimen (p < 0.0001, t-test). Compared to the NKCC1 staining intensity of neurons in the control group (measuring 1000 cells each), the IA value of dysmorphic neurons was significantly increased (p < 0.05, t'-test Cochran & Cox method). Intracytoplasmic concentration of KCC2 was evident in dysmorphic neurons but not in the other mature neurons. Most of the balloon cells were negative for NKCC1, except for few balloon cells showing sparse colored particles. The expression of KCC2 was negative in all balloon cells. CONCLUSIONS: The changes in the expression of NKCC1 and KCC2 may indicate that dysmorphic neurons were in a state similar to that of immature neurons. This state may be related to the abnormal electrophysiology of epilepsy. The difference between the number of GAD67 positive cells in the lesion site and the remote site of the same case may be an evaluation index of the effectiveness of surgery.

Tranexamic acid in intracerebral hemorrhage: a meta-analysis.

OBJECTIVE: Evidence-based medicine was used to evaluate the efficacy and safety of tranexamic acid in patients with intracerebral hemorrhage. METHODS: Pubmed (MEDLINE), Embase, and Cochrane Library were searched from January 2001 to October 2020 for randomized controlled trials (RCTs), cohort studies, and retrospective case series .The Jadad scale and RevMan software version 5.3 were used for literature quality assessment and meta-analysis. RESULTS: In total, 4 randomized controlled trials and 1 retrospective case series with 2808 participants were included in the meta-analysis. Compared with control intervention in intracerebral hemorrhage, tranexamic acid could significantly reduce growth of hemorrhagic mass (odds ratio (OR) =0.81; 95% confidence interval(CI)=0.68 to 0.99; p = 0.04) and Modified Rankin Scale score (MRS) at 90 days at 0-3 (OR = 1.20; 95% CI = 1.00 to 1.43; p = 0.05), mortality by day 90 (OR= 1.03; 95% CI= 0.85-1.25; p = 0.77) and major thromboembolic events (OR= 1.14; 95% CI= 0.73-1.77; p = 0.58). CONCLUSIONS: Treatment with tranexamic acid could reduce hematoma expansion in intracerebral hemorrhage, and the treatment was safe with no increase in thromboembolic complications. But showed no notable impact on good functional outcomes and mortality.

Investigation on the molecular, electronic and spectroscopic properties of rosmarinic acid: an intuition from an experimental and computational perspective.

Various drugs such as corticosteroids, salbutamol, and ß2 agonist are available for the treatment of asthma an inflammatory disease and its symptoms, although the ingredient and the mode of action of these drugs are not clearly elucidated. Hence this research aimed at carrying out improved scientific research with respect to the use of natural product rosmarinic acid which poses minima, side effects. Herein, we first carried out extraction, isolation, and spectroscopic (FT-IR, 1H-NMR and 13C-NMR) investigation, followed by molecular modeling analysis on the naturally occurring rosmarinic acid extracted from Rosmarinus officinalis. A detailed comparison of the experimental and theoretical vibrational analysis has been carried out using five DFT functionals: BHANDH, HSEH1PBE, M06-2X, MPW3PBE and THCTHHYB with the basis set 6-311++G (d, p) to investigate into the structural, reactivity, and stability of the isolated compound. Frontier molecular orbital analysis and appropriate quantum descriptors were calculated. Results showed that the compound was more stable at M06-2X and more reactive at HSEH1PBE with an energy gap of 6.43441 eV and 3.8047 eV, respectively, which was later affirmed by the global quantum reactivity parameters. From natural bond orbital analysis, π* →π* is the major contributor to electron transition with the summation perturbation energy of 889.57 kcal/mol, while π →π* had the perturbation energy totaling of 145.3 kcal/mol. Geometry analysis shows BHANDH to have lower bond length values and lesser deviation from 120° in carbon-carbon angle. The potency of the title molecule as an asthma drug was tested via a molecular docking approach and the binding score of -8.2 kcal/mol was observed against -7.0 of salbutamol standard drug, suggesting romarinic acid as a potential natural organic treatment for asthma.Communicated by Ramaswamy H. Sarma.

Reliability and validity of prognostic indicators for Guillain-Barré syndrome in children.

AIM: To explore the clinical characteristics and prognostic predictors of Guillain-Barré syndrome (GBS) in Chinese paediatric patients. METHOD: The clinical features of children with GBS hospitalized in the Children's Hospital of Chongqing Medical University were summarized retrospectively. The correlation between the Erasmus GBS Outcome Score (EGOS)/modified Erasmus GBS Outcome Score (mEGOS), GBS disability score (GDS)/modified Rankin Scale (MRS), Erasmus GBS Respiratory Insufficiency Score (EGRIS), and mechanical ventilation were evaluated. RESULTS: One hundred forty-two patients (86 males, 56 females; median 62.50 months [interquartile range 41.00-97.50]) with classic GBS were enrolled in the study. In the present GBS cohort, 134 (94.37%) patients could walk independently (GDS ≤2) and 121 (85.21%) could manage without assistance (MRS ≤2) at 6 months. Eighteen (12.68%) patients with GBS required mechanical ventilation. The performance of mEGOS on admission, mEGOS on day 7, and EGOS-predicted GDS outcome at 4 weeks, 3 months, and 6 months in the paediatric patients with GBS admitted within 2 weeks of disease onset and that of the MRS outcome were evaluated. The EGRIS in individuals who required mechanical ventilation was significantly higher than in patients without mechanical ventilation (median = 6 vs median = 3, p < 0.001). INTERPRETATION: In Chinese paediatric patients with GBS who were admitted 2 weeks after disease onset, the mEGOS and EGOS are validated indicators for the prediction of clinical outcomes 6 months after onset. EGRIS is helpful in predicting the implementation of mechanical ventilation in the acute phase. WHAT THIS PAPER ADDS: The Erasmus Guillain-Barré syndrome (GBS) Outcome Score (EGOS) and modified EGOS are reliable prognostic predictors in paediatric patients with GBS. The Erasmus GBS Respiratory Insufficiency Score (EGRIS) is an effective predictor of mechanical ventilation in paediatric patients with GBS. An EGRIS of ≥5 indicates a high risk of mechanical ventilation in the acute phase.

Literature analysis on the status quo of performance appraisal of pharmacy intravenous admixture services in China / 中国药房

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.

Complete chloroplast genome sequencing and phylogeny of wild Atractylodes lancea from Yuexi, Anhui province / 中国中药杂志

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.

Analysis of clinical phenotypes and genetic variants in two children with sporadic cleidocranial dysplasia / 中华医学遗传学杂志

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.

Clinical phenotype and genetic analysis of twelve children with ring chromosomes / 中华医学遗传学杂志

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.

Application value of CNV-seq for the prenatal diagnosis of women with high-risk pregnancies / 中华医学遗传学杂志

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.

Mechanism of Qiwei Guibao Granules in treatment of premature ovarian failure based on proteomics / 中国中药杂志

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.

Clinical phenotype and genetic analysis of a fetus with Glutaracidemia type II C / 中华医学遗传学杂志

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.

Clinical and genetic analysis of three children with Menkes disease due to variants of ATP7A gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic etiology of three children with Menkes disease.@*METHODS@#Three children who had presented at the Children's Medical Center, the Affiliated Hospital of Guangdong Medical University from January 2020 to July 2022 were selected as the study subjects. Clinical data of the children were reviewed. Genomic DNA was extracted from peripheral blood samples of the children, their parents and sister of child 1. Whole exome sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing, copy number variation sequencing (CNV-seq), and bioinformatic analysis.@*RESULTS@#Child 1 was a 1-year-and-4-month male, and children 2 and 3 were monozygotic twin males aged 1-year-and-10-month. The clinical manifestations of the three children have included developmental delay and seizures. WES showed that child 1 has harbored a c.3294+1G>A variant of the ATP7A gene. Sanger sequencing confirmed that his parents and sister did not carry the same variant, suggesting that it was de novo. Children 2 and 3 had carried a c.77266650_77267178del copy number variation. CNV-seq results showed that their mother has carried the same variant. By searching the HGMD, OMIM and ClinVar databases, the c.3294+1G>A was known to be pathogenic. No carrier frequency has been recorded in the 1000 Genomes, ESP, ExAC and gnomAD databases. Based on the Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics (ACMG), the ATP7A gene c.3294+1G>A variant was predicted to be pathogenic. The c.77266650_77267178del variant has involved exons 8 to 9 of the ATP7A gene. ClinGen online system score for it was 1.8, which was also considered to be pathogenic.@*CONCLUSION@#The c.3294+1G>A and c.77266650_ 77267178del variants of the ATP7A gene probably underlay the Menkes disease in the three children. Above finding has enriched the mutational spectrum of Menkes disease and provided a basis for clinical diagnosis and genetic counseling.

Primary Ovarian Small Cell Carcinoma of Pulmonary Type: Analysis of 6 Cases and Review of 31 Cases in the Literatures / 中国医学科学杂志(英文版)

Objective Primary ovarian small cell carcinoma of pulmonary type (SCCOPT) is a rare ovarian tumor with a poor prognosis. The platinum-based chemotherapy is the standard treatment. However, there is little research on the clinical characteristics of SCCOPT and the potential benefits of other treatments due to its low incidence. The study aims to investigate clinicopathological characteristics and treatment of SCCOPT.Methods We summarized the clinical, imaging, laboratorical and pathological characteristics of 37 SCCOPT cases, in which 6 cases were admitted to the Gansu Provincial Hospital from the year of 2008 to 2022 and 31 cases reported in 17 English and 3 Chinese literatures.Results The median age of the studied SCCOPT cases (n=37) was 56.00 (range, 22-80) years. Almost 80% of them had a stage Ⅲ or Ⅳ tumor. All patients underwent an operation and postoperative chemotherapy. Nevertheless, all cases had a poor prognosis, with a median overall survival time of 12 months. Immunohistochemically, the SCCOPT of all patients showed positive expressions of epithelial markers, such as CD56 and sex-determining region of Y chromosome-related high-mobility-group box 2 (SOX-2), and negative expressions of estrogen receptor, progesterone receptor, vimentin, Leu-7, and somatostatin receptor 2. The tumor of above 80% cases expressed synaptophysin. Only a few cases expressed neuron-specific enolase, chromogranin A, and thyroid transcription factor-1. Conclusions SCCOPT had a poor prognosis. SOX-2 could be a biomarker to be used to diagnose SCCOPT.

Evaluation of the physicochemical properties of alkali-soluble polysaccharide from Poria and its application in diclofenac sodium sustained-release tablets / 药学学报

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.

Effects of the expression of miR-375 on the proliferation and invasion of choroidal melanoma cells / 国际眼科杂志(Guoji Yanke Zazhi)

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&#x003C;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&#x003C;0.05), while the OD values of the cells in the inhibitor group at 24, 48, 72, and 96h were increased(P&#x003C;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&#x003C;0.05), while it was decreased in the inhibitor group(10.13±2.17)%(P&#x003C;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&#x003C;0.05), while the number of migration cell and the number of invasion cell in the inhibitor group were increased(P&#x003C;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.

Effect of Anmeidan on Serum Levels of BDNF， GFAP， and Irisin in Patients with Chronic Insomnia / 中国实验方剂学杂志

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.