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Abstract Objective: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. Method: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. Results: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4% (p = 0.006). Conclusion: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.
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Objective To investigate the environmental contamination related to first patient with carbapenem-re-sistant Acinetobacter baumannii(CRAB)infection and the infection status of relevant patients in a newly established intensive care unit(ICU)of a hospital in Tibetan area,and analyze the transmission risk.Methods From the ad-mission in ICU of a patients who was first detected CRAB on November 15,2021 to the 60th day of hospitalization,all patients who stayed in ICU for＞48 hours were performed active screening on CRAB.On the 30th day and 60th day of the admission to the ICU of the first CRAB-infected patient,environment specimens were taken respectively 2 hours after high-frequency diagnostic and therapeutic activities but before disinfection,and after disinfection but before medical activities.CRAB was cultured with chromogenic culture medium.Results Among the 13 patients who were actively screened,1 case was CRAB positive,he was transferred from the ICU of a tertiary hospital to the ICU of this hospital on November 19th.On the 40th day of admission to the ICU,he had fever,increased frequency for sputum suction,and CRAB was detected.The drug sensitivity spectrum was similar to that of the first case,and he also stayed in the adjacent bed of the first case.64 environmental specimens were taken,and 9 were positive for CRAB,with a positive rate of 14.06％,8 sampling points such as the washbasin,door handle and bed rail were positive for CRAB after high-frequency diagnostic and therapeutic activities.After routine disinfection,CRAB was detected from the sink of the washbasin.Conclusion For the prevention and control of CRAB in the basic-level ICU in ethnic areas,it is feasible to conduct risk assessment on admitted patients and adopt bundled prevention and con-trol measures for high-risk patients upon admission.Attention should be paid to the contaminated areas(such as washbasin,door handle,and bed rail)as well as the effectiveness of disinfection of sink of washbasin.
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Wenzhou has improved its environmental quality because of comprehensive environmental remediation; nevertheless, the semen quality of infertile males remains unclear. This study determined whether better environmental quality improved semen quality in this region. We recorded semen quality data from 22 962 infertile males from January 2014 to November 2019 at the Center for Reproductive Health of The First Affiliated Hospital of Wenzhou Medical University (Wenzhou, China). Patients were predominantly 30-35 years old (33.1%) and workers (82.0%), with high school education or lower (77.6%); more than a half of the patients (52.6%) were Wenzhou household registration; and most patients (77.5%) had abnormal semen quality. Patients who were older than 40 years and workers, and those with Wenzhou household registration, had significantly worse semen quality (all P < 0.05). From 2014 to 2019, progressive sperm motility, total sperm motility, and semen volume showed increasing linear trends in all patients (P = 0.021, 0.030, and 0.005, respectively), yet normal sperm morphology showed a linearly decreasing trend (P = 0.046). Sensitivity analyses for subgroups yielded similar results. In conclusion, the improvement of environmental quality and better function of the accessory glands are associated with progressive sperm motility, total sperm motility, and semen volume. Normal sperm morphology is influenced by occupational exposures and personal lifestyle and does not improve with environmental quality.
Subject(s)
Male , Humans , Adult , Semen Analysis , Semen , Sperm Count , Sperm Motility , Infertility, Male , SpermatozoaABSTRACT
OBJECTIVE@#To explore the effect of electroacupuncture (EA) intervention on the vasoconstriction of cerebral artery smooth muscle cells after cerebral infarction.@*METHODS@#Male Wistar rats were randomly divided into 3 groups by a random number table: the model group (n=24), the EA group (n=24), and the normal group (n=6). The model and the EA groups were divided into different time subgroups at 0.5, 1, 3, and 6 h after middle cerebral artery occlusion (MCAO), with 6 rats in each subgroup. MCAO model was established using intraluminal suture occlusion method. The EA group was given EA treatment at acupoint Shuigou (GV 26) instantly after MCAO for 20 min. The contents of cerebrovascular smooth muscle MLCK, the 3 subunits of myosin light chain phosphatase (MLCP) MYPT1, PP1c-δ and M20, as well as myosin-ATPase activity were detected using immunohistochemistry and Western blotting.@*RESULTS@#The overall expression level of the MYPT1 and PP1c-δ in the model group was significantly higher (P<0.01). After EA intervention, the 0.5 h group expression level was close to that of the normal group (P>0.05), and the other subgroups were still significantly higher than the normal group (P<0.01). After EA intervention, the expression level of each subgroup was significantly lower than the corresponding model group. There was a significant difference between the 0.5 and 1 h subgroups (P<0.01), while a difference was also observed between the 3 and 6 h subgroups (P<0.05). The dynamic change rule gradually increased with the prolongation of infarction time within 6 h after infarction.@*CONCLUSION@#EA intervention can inhibit contraction of cerebral vascular smooth muscle cells and regulate smooth muscle relaxation by regulating MLCK pathway.
Subject(s)
Rats , Male , Animals , Rats, Wistar , Electroacupuncture , Cerebral Infarction/metabolism , Muscle, Smooth , Acupuncture Points , Brain Ischemia/therapyABSTRACT
Nasopharyngeal carcinoma (NPC) is the third most common malignancy with a high recurrence and metastasis rate in South China. Natural compounds extracted from traditional Chinese herbal medicines have been developed and utilized for the treatment of a variety of cancers with modest properties and slight side effects. Maackiain (MA) is a type of flavonoid that was first isolated from leguminous plants, and it has been reported to relieve various nervous system disorders and exert anti-allergic as well as anti-inflammatory effects. In this study, we demonstrated that MA inhibited proliferation, arrested cell cycle and induced apoptosis in nasopharyngeal carcinoma CNE1 and CNE2 cells in vitro and in vivo. The expression of the related proteins associated with these processes were consistent with the above effects. Moreover, transcriptome sequencing and subsequent Western blot experiments revealed that inhibition of the MAPK/Ras pathway may be responsible to the anti-tumor effect of MA on NPC cells. Therefore, the effects of MA and an activator of this pathway, tertiary butylhydroquinone (TBHQ), alone or combination, were investigated. The results showed TBHQ neutralized the inhibitory effects of MA. These data suggest that MA exerts its anti-tumor effect by inhibiting the MAPK/Ras signaling pathway and it has the potential to become a treatment for patients with NPC.
Subject(s)
Humans , Nasopharyngeal Carcinoma/pathology , Cell Line, Tumor , Cell Proliferation , Apoptosis , Signal Transduction , Nasopharyngeal Neoplasms/pathologyABSTRACT
Polymer nanoparticles generally refer to hydrophobic polymers-based nanoparticles, which have been extensively studied in the nanomedicine field due to their good biocompatibility, efficient long-circulation characteristics, and superior metabolic discharge patterns over other nanoparticles. Existing studies have proved that polymer nanoparticles possess unique advantages in the diagnosis and treatment of cardiovascular diseases, and have been transformed from basic researches to clinical applications, especially in the diagnosis and treatment of atherosclerosis (AS). However, the inflammatory reaction induced by polymer nanoparticles would induce the formation of foam cells and autophagy of macrophages. In addition, the variations in the mechanical microenvironment of cardiovascular diseases may cause the enrichment of polymer nanoparticles. These could possibly promote the occurrence and development of AS. Herein, this review summarized the recent application of polymer nanoparticles in the diagnosis and treatment of AS, as well as the relationship between polymer nanoparticles and AS and the associated mechanism, with the aim to facilitate the development of novel nanodrugs for the treatment of AS.
Subject(s)
Humans , Polymers/chemistry , Cardiovascular Diseases , Nanoparticles/chemistry , Drug Delivery Systems , Atherosclerosis/pathologyABSTRACT
According to the method of predicting the physical properties of oily powder based on the additive physical properties of Chinese medicinal powder, Dioscoreae Rhizoma and calcined Ostreae Concha with high sieve rate and good fluidity were mixed and crushed with Persicae Semen, Platycladi Semen, Raphani Semen, Ziziphi Spinosae Semen, and other typical oily materials with high fatty oil content in proportion to obtain 23 mixed powders. Fifteen physical properties such as bulk density, water absorption, and maximum torque force were measured, and the physical properties of typical oily powders were predicted. When the mixing and grinding ratio was in the range of 5∶1-1∶1, the r value in the correlation equation between the weighted average score of the mixed powder and the powder proportion ranged from 0.801 to 0.986, and the linearity was good, indicating that the method of predicting the physical properties of oily powder based on the additive physical properties of traditional Chinese medicine(TCM)powder was feasible. The results of cluster analysis showed that the classification boundaries of the five kinds of TCM materials were clear, and the similarity of the physical fingerprints of powdery and oily materials decreased from 80.6% to 37.2%, which solved the problem of fuzzy classification boundaries of powdery and oily materials due to the lack of representativeness of oily material model drugs. The classification of TCM materials was optimized, laying a foundation for optimizing the prediction model of the prescription of personalized water-paste pills.
Subject(s)
Medicine, Chinese Traditional , Drugs, Chinese Herbal , Powders , PrescriptionsABSTRACT
OBJECTIVE@#To summarize the effectiveness of the temporal island flap pedicled with the perforating branch of zygomatic orbital artery for repairing defects after periocular malignant tumor resection.@*METHODS@#Between January 2015 and December 2020, 15 patients with periocular malignant tumors were treated. There were 5 males and 10 females with an average age of 62 years (range, 40-75 years). There were 12 cases of basal cell carcinoma and 3 cases of squamous carcinoma. The disease duration ranged from 5 months to 10 years (median, 2 years). The size of tumors ranged from 1.0 cm×0.8 cm to 2.5 cm×1.5 cm, without tarsal plate invasion. After extensive resection of the tumors, the left defects in size of 2.0 cm×1.5 cm to 3.5 cm×2.0 cm were repaired with the temporal island flap pedicled with the perforating branch of zygomatic orbital artery via subcutaneous tunnel. The size of the flaps ranged from 3.0 cm×1.5 cm to 5.0 cm×2.0 cm. The donor sites were separated subcutaneously and sutured directly.@*RESULTS@#All flaps survived after operation and the wounds healed by first intention. The incisions at donor sites healed by first intention. All patients were followed up 6-24 months (median, 11 months). The flaps were not obviously bloated, the texture and color were basically the same as the surrounding normal skin, and the scars at recipient sites were not obviously. There was no complication such as ptosis, ectropion, or incomplete closure of the eyelids and recurrence of tumor during follow-up.@*CONCLUSION@#The temporal island flap pedicled with the perforating branch of zygomatic orbital artery can repair the defects after periorbital malignant tumors resection and has the advantages of reliable blood supply, flexible design, and good morphology and function.
Subject(s)
Male , Female , Humans , Middle Aged , Plastic Surgery Procedures , Skin Transplantation , Soft Tissue Injuries/surgery , Treatment Outcome , Surgical Flaps , Arteries/surgery , Carcinoma, Squamous Cell/surgery , Skin Neoplasms/surgery , Perforator Flap/blood supplyABSTRACT
Based on the androgen receptor(AR)/mammalian target of rapamycin(mTOR)signaling pathway, the effects of Xihuang Pills-medicated serum on the proliferation and apoptosis of prostate cancer LNCaP cells were investigated. The drug-containing serum of SD rats was prepared by intragastric administration of Xihuang Pills suspension. The effects of low-, medium-, and high-dose Xihuang Pills-containing serum on the in vitro proliferation of LNCaP cells were detected by cell counting kit-8(CCK-8). Flow cytometry was used to detect the apoptosis level of LNCaP cells after intervention with different concentrations of Xihuang Pills. Protein expression of cleaved cysteinyl aspartate-specific proteinase caspase-3(cleaved caspase-3), B-cell lymphoma-2(Bcl-2), and AR as well as the phosphorylation level of mTOR protein were detected by Western blot. The results showed that compared with the blank serum, the drug-medicated serum could blunt the activity of LNCaP cells. Low-, medium-, and high-dose Xihuang Pills-containing serum could significantly increase the cell apoptosis rate, increase the expression of cleaved caspase-3 protein, decrease the expression of Bcl-2 protein, reduce the expression of AR protein, and down-regulate the level of phosphorylated mTOR(p-mTOR). To study the effect of Xihuang Pills on the growth of LNCaP cells in vivo, different doses of Xihuang Pills were used to intervene in the subcutaneous graft model in nude mice inoculated with LNCaP cells. The expression levels of AR, mTOR, p-mTOR, Bcl-2, and cleaved caspase-3 were detected by Western blot. The results showed that the volumes of subcutaneous graft tumor in the low-dose, medium-dose, and high-dose Xihuang Pills groups significantly decreased compared with that in the model group. The weight of subcutaneous transplanted tumor in each group with drug intervention was significantly lower than that in the model group. Compared with the model group, the low-dose, medium-dose, and high-dose Xihuang Pills groups showed increased cleaved caspase-3 protein expression, decreased Bcl-2 and AR protein expression, and reduced p-mTOR protein expression. Further experiments showed that AR agonist R1881 could block the anti-proliferation and pro-apoptotic effects of Xihuang Pills. The mechanism of Xihuang Pills against prostate cancer is related to the inhibition of the AR/mTOR signaling pathway, inhibition of LNCaP cell proliferation, and induction of apoptosis in cancer cells.
Subject(s)
Humans , Male , Mice , Rats , Animals , Caspase 3/metabolism , Mice, Nude , Cell Line, Tumor , Rats, Sprague-Dawley , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Prostatic Neoplasms/pathology , Cell Proliferation , Apoptosis , Proto-Oncogene Proteins c-bcl-2/metabolism , Mammals/metabolismABSTRACT
Craniovertebral junction anomalies are a group of diseases characterized by the pathological changes of occipital bone,atlantoaxial bone,cerebellar tonsil,surrounding soft tissue,and nervous system,which are caused by a variety of factors.Chiari malformation is a common type of craniovertebral junction anomalies,the conventional surgical therapy of which is posterior fossa decompression.Currently,scholars represented by Goel have proposed a new theory on the classification,pathogenesis,and treatment of Chiari malformation based on posterior atlantoaxial fixation (Goel technique).This article introduces the progress in Goel technique,aiming to provide reference for the clinical work.
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Humans , Arnold-Chiari Malformation/surgeryABSTRACT
Objective:To investigate the risk factors for the occurrence and poor in-hospital prognosis in patients with peripartum cardiomyopathy (PPCM).Methods:The clinical data of 35 patients with PPCM and 35 healthy pregnant women in Xuanwu Hospital, Capital Medical University and Beijing Friendship Hospital Affiliated to Capital Medical University from January 2003 to January 2022 were retrospectively analyzed. The personal histories, laboratory examination, imaging examination, cardiac function outcome, etc were collected. According to the left ventricular ejection fraction (LVEF) at discharge, the patients with PPCM were divided into in-hospital recovery group (LVEF≥50%, 18 cases) and prolonged disease group (LVEF<50%, 17 cases). Multivariate Logistic regression analysis was used to analyze independent risk factors of poor in-hospital prognosis in patients with PPCM.Results:Among 35 patients with PPCM, the age was (29.81 ± 5.37) years old, 17 cases (48.57%) complicated with gestational hypertension, 6 cases (17.14%) complicated with gestational diabetes mellitus, 24 cases (68.57%) of New York Heart Association (NYHA) cardiac function classification was Ⅲ to Ⅳ class, and 4 cases died (11.43%). The gestational age in patients with PPCM was significantly shorter than that in healthy pregnant women: (36.26 ± 4.27) weeks vs. (38.54 ± 4.59) weeks, the rates of multiple pregnancy and gestational hypertension were significantly higher than those in healthy pregnant women: 17.14% (6/35) vs. 2.86% (1/35) and 48.57% (17/35) vs. 11.43% (4/35), and there were statistical differences ( P<0.05 or <0.01). Compared with hospital recovery group, the patients in protracted disease group had shorter gestational age, larger left ventricular end-diastolic diameter, higher serum creatinine, C-reactive protein and amino-terminal pro-brain natriuretic peptide (NT-proBNP), worse NYHA cardiac function classification, and there were statistical differences ( P<0.05 or <0.01); but there were no statistical difference in LVEF at the first diagnosis and troponin I between two groups ( P>0.05). Multivariate Logistic regression analysis result showed that elevated creatinine was an independent risk factor for poor in-hospital prognosis in patients with PPCM ( OR = 4.554, 95% CI 1.536 to 13.684, P = 0.018). Conclusions:The gestational hypertension may be a risk factor for PPCM. The gestational hypertension, earlier onset time, enlarged left ventricular end-diastolic diameter, high NT-proBNP, high C-reactive protein, high creatinine and high cardiac function NYHA classification may be risk factors for poor in-hospital prognosis in patients with PPCM; and elevated creatinine is an independent risk factor for poor in-hospital prognosis in patients with PPCM.
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Objective Calculus Bovis(CB)is a kind of valuable traditional Chinese medicine,which has been used in clinic for a long time.It has been shown to have significant anti-stroke,anti-inflammatory and anti-tumor effects.But its mechanism for treating Prostate cancer(PCa)remains unclear.The purpose of this study was to explore the target and mechanism of its action in the treatment of prostate cancer throμgh network pharmacology and in vitro and in vivo experiments.Methods The effective compounds of Calculus Bovis were collected by TCM pharmacology database and analysis platform(TCMSP).Search for potential compound targets in TCMSP.Search the Drμgbank,GeneCards,OMIM,PharmGkb,and TTD databases for disease targets associated with prost cancer.Disease and compound targets were integrated in the STRING database to construct their interaction network(PPI)to reveal the key targets of compound treatment for prostate cancer.In order to elucidate the mechanism of Calculus Bovis in the treatment of prostate cancer,GO functional enrichment and KEGG pathway enrichment analysis were conducted using Cytoscape software.The mechanism of treating prostate cancer with Calculus Bovis was studied in vitro and in vivo.Results A total of 11 compounds with anti-prostate cancer activity were identified.Oleanolic acid,ursolic acid,ergosterol,deoxycorticosterone,methylcholine and cholverdin were potential effective components.A total of 367 targets of Calculus Bovis compounds and 2152 targets of prostate cancer were found.The core targets of Calculus Bovis in the treatment of prostate cancer included TP53,STAT3,AKT1,HSP90AA1,ESR1,SRC,JUN,RELA,CCND1,CDKN1A,EGFR,AR,etc.The biological functions of Calculus Bovis mainly involve oxidative stress response,response to steroid hormones,cell response to chemical stress,peptide-serine modification and phosphorylation,and protein serine/threonine kinase activity.Calculus Bovis treatment of prostate cancer mainly involves PI3K-AKT signaling pathway,TNF signaling pathway,MAPK signaling pathway,etc.In vitro and in vivo experiments showed that Calculus Bovis promoted apoptosis of PC3 cells of prostate cancer by inhibiting PI3K-AKT signaling pathway.Conclusion Calculus Bovis has a therapeutic effect on prostate cancer,and its function is related to inhibiting PI3K-AKT signaling pathway and promoting apoptosis of cancer cells.
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Objective: To explore the clinical, pathological, diagnostic, treatment, and prognostic features of children with mature B-cell lymphoma (MBCL) . Methods: This retrospective study included pediatric patients with MBCL with chromosome 11 long-arm abnormalities who were diagnosed and treated at our hospital from December 2018 to February 2023. Results: Among the 11 pediatric patients with MBCL, nine were male and two were female, with a median age of 9 (2-13) years and a median disease course of 1.8 (0.5-24) months. The clinical manifestations were cervical lymph node enlargement in four patients, nasal congestion and snoring in four patients, abdominal pain in two patients, and difficulty breathing in one patient. There were seven cases of Burkitt's lymphoma, two of follicular lymphoma, and two of advanced B-cell lymphoma according to the pathological morphology examination. No patients had central nervous system or bone marrow involvement, and no extensive metastasis was observed on B-ultrasound or positron emission tomography-computed tomography (PET/CT). One patient had a huge tumor lesion. The Revised International Pediatric Non-Hodgkin Lymphoma Staging System classified four patients as stage Ⅱ, five as stage Ⅲ, and two as stage Ⅳ. 11q probe detection showed five cases of 11q gain, three of 11q loss, and three of both gain and loss. FISH showed positive MYC expression in three patients, including eight with advanced B-cell lymphoma with 11q abnormalities and three with Burkitt's lymphoma with 11q abnormalities. According to the 2019 edition of the National Health Commission's diagnostic and treatment guidelines for invasive MBCL in children, one patient was classified as Group A, two as Group B, and eight as Group C. Early evaluation of the efficacy showed complete remission. After mid-term evaluation, the intensity of chemotherapy was reduced in Group B and Group C. Among two cases of chemotherapy, the remaining nine cases had a median follow-up of 32 (6-45) months, and none had event-related survival. Conclusion: The incidence of MBCL with 11q abnormalities in children is low, clinical symptoms are mild, and progression is slow. The absence of MYC, BCL2, BCL6 rearrangements, C-MYC negative and 11q abnormalities on FISH is an important diagnostic indicator, and reducing the intensity of chemotherapy can improve prognosis.
Subject(s)
Humans , Female , Male , Child , Adolescent , Burkitt Lymphoma/genetics , Chromosomes, Human, Pair 11 , Positron Emission Tomography Computed Tomography , Retrospective Studies , Lymphoma, Follicular , Chromosome AberrationsABSTRACT
Objective: To explore the relationship between pathogenic gene, mutation and phenotype of left ventricular noncompaction (LVNC) patients and their family members. Methods: The subjects were the proband with LVNC and her family members. The medical history including electrocardiogram, echocardiography and cardiac magnetic resonance examination of the proband and family members were collected. Whole exome sequencing of the proband was performed, bioinformatics analysis focused on the genes related to hereditary cardiomyopathy. Candidate pathogenic sites were validated by Sanger sequencing. The clinical interpretation of sequence variants were classified according to American College of Medical Genetics and Genomics (ACMG) guidelines. Results: The proband carried a heterozygous variation of the MYBPC3 gene c.C2827T and the MYH7 gene c.G2221C. The proband's sister carried heterozygous variation of MYBPC3 gene c.C2827T. According to the ACMG guidelines, the variant was determined to be pathogenic. Conclusion: The missense variant of MYBPC3 gene c.C2827T and MYH7 gene c.G2221C are identified from the proband with LVNC and her family member, which provides a genetic basis for clinical diagnosis and genetic counseling of the patients and the family members with LVNC.
Subject(s)
Female , Humans , Cardiac Myosins/genetics , Heart Defects, Congenital , Mutation , Mutation, Missense , Myosin Heavy Chains/genetics , Pedigree , PhenotypeABSTRACT
Objective: To explore the relationship between pathogenic gene, mutation and phenotype of left ventricular noncompaction (LVNC) patients and their family members. Methods: The subjects were the proband with LVNC and her family members. The medical history including electrocardiogram, echocardiography and cardiac magnetic resonance examination of the proband and family members were collected. Whole exome sequencing of the proband was performed, bioinformatics analysis focused on the genes related to hereditary cardiomyopathy. Candidate pathogenic sites were validated by Sanger sequencing. The clinical interpretation of sequence variants were classified according to American College of Medical Genetics and Genomics (ACMG) guidelines. Results: The proband carried a heterozygous variation of the MYBPC3 gene c.C2827T and the MYH7 gene c.G2221C. The proband's sister carried heterozygous variation of MYBPC3 gene c.C2827T. According to the ACMG guidelines, the variant was determined to be pathogenic. Conclusion: The missense variant of MYBPC3 gene c.C2827T and MYH7 gene c.G2221C are identified from the proband with LVNC and her family member, which provides a genetic basis for clinical diagnosis and genetic counseling of the patients and the family members with LVNC.
Subject(s)
Female , Humans , Cardiac Myosins/genetics , Heart Defects, Congenital , Mutation , Mutation, Missense , Myosin Heavy Chains/genetics , Pedigree , PhenotypeABSTRACT
Objective: To summarize changes of serum immunoglobulin levels before and after chemotherapy in children with Burkitt lymphoma (BL), so as to investigate the effects of chemotherapy and rituximab on serum immunoglobulin levels in children with BL. Methods: Clinical data of 223 children with newly diagnosed Burkitt lymphoma at Beijing Children's Hospital from January 2009 to April 2017 were analyzed retrospectively. They were treated according to the modified LMB 89 regimen and some of them received combined rituximab therapy during the chemotherapy. The serum immunoglobulin (IgA, IgM, IgG) before chemotherapy, at the time of discontinuing chemotherapy, as well as 6, 12, 24, 36 months after chemotherapy were collected. Changes of serum IgA, IgM and IgG with time among different treatment groups were compared using repeated measures ANOVA. Results: According to risk group, 223 children were devided into group B（n=53）and group C（n=170）. Before chemotherapy, 109 cases (48.9%) were combined with hypogammaglobulinemia. The serum IgA, IgM, and IgG levels of all the patients were (0.9±0.7), 1.2 (0.5, 1.3) and (7.2±2.9) g/L before chemotherapy, (0.5±0.4), 0.2 (0.1, 0.3) and (6.3±2.3) g/L at the time of discontinuing chemotherapy (t=13.63, Z=-11.99, t=4.57, all P<0.05). There were statistical difference in IgA, IgM levels of group B and IgA, IgM, IgG levels of group C before chemotherapy and at the time of discontinuing chemotherapy (t=8.86, Z=-6.28, t=11.19, Z=-10.15, t=4.50, all P<0.05). The differences of serum IgA and IgG levels at the time after chemotherapy among patients treated with chemotherapy alone and those treated with chemotherapy combined rituximab in group B and C were significant (F=5.38, P=0.002 and F=4.22, P=0.007). Conclusions: Approximately half of children with BL have already existed hypogammaglobulinemia at initial diagnosis prior to the start of treatment. The modified LMB 89 regimen have significant effect on humoral immunity of children with BL. In the process of immune reconstruction after chemotherapy, rituximab has more significant effect on serum IgA and IgG levels in BL patients.
Subject(s)
Child , Humans , Agammaglobulinemia , Burkitt Lymphoma/drug therapy , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Retrospective Studies , Rituximab/therapeutic useABSTRACT
Objective:To explore the perinatal management of patients with WD during pregnancy, and to determine its genetic etiology and the possibility of fetal morbidity using the genetic detection of amniotic fluid and umbilical cord blood.Method:In terms of fine management during the perinatal period, a case of K-F ring was found in the Ophthalmology Department of Beijing Friendship Hospital, Capital Medical University in March 2019 due to eye astringency and eye swelling, and the hepatology department further diagnosed WD for one artificial abortion. After the second pregnancy in October 2020, multidisciplinary consultation and standardized treatment during pregnancy including gynecology and obstetrics, liver disease center, anesthesiology department, gastroenterology department and nutrition department were carried out. The genomes of patients' venous blood, amniotic fluid and umbilical cord blood were extracted and analyzed for ATP7B gene variation by Sanger sequencing.Result:Through multi-disciplinary collaborative management, the patient gave birth successfully in the case of pregnancy complicated with liver cirrhosis, portal hypertension, splenomegaly with hyperfunction, thrombocytopenia, anemia, esophageal and gastric varices and other complications. The phenotype of the newborn was normal, and the Apgar score was 10-10-10. Sequencing results showed that the patient had ATP7B p.Arg778Leu and p.Val890Met, which were missense heterozygous variants reported in the mutation database, and ACMG was classified as pathogenic variants. The results of amniotic fluid and umbilical cord blood showed that the fetus had only p.Arg778Leu single heterozygous variation, and it was predicted that there would be no clinical phenotype of WD.Conclusion:Perinatal multidisciplinary collaborative management has important protective significance for the successful pregnancy of patients with WD. Genetic screening of amniotic fluid and umbilical cord blood is conducive to early detection of fetal WD.
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Aiming to solve the poor compactibility of the alcoholic extract of Zingiberis Rhizoma(ZR), this study explored the feasibility of its physical modification using co-spray drying with a small amount of hydroxypropyl methyl cellulose(HPMC). Based on the univariate analysis, the influence of two independent variables(the HPMC content in the product and the solid content of spray material) on the powder properties and tablet properties of the dried product was investigated by the central composite design. With the tensile strength and disintegration time of the tablets as the evaluation indexes, the optimal prescription was determined as follows: the HPMC content was 15% and the solid content of spray material was 25.6%. The accuracy of the regression model established for predicting tensile strength and disintegration time of tablets was verified, and the results revealed that the measured values were close to the predicted ones with deviations of 0.47% and-8.2%, indicating good prediction and reproducibility of the model. The tensile strength(4.24 MPa) of tablets prepared with the optimal prescription was 3.59 times that(1.18 MPa, far lower than the baseline of 2 MPa for qualified tablets) with the spray-dried powder of the ZR. On the other hand, due to the addition of HPMC, the disintegration time of tablets increased from 7.3 min to 24.6 min. On the whole, this study provided a new strategy to solve the common problem of poor compactibility of raw Chinese medicinal materials, which facilitated the successful preparation of Chinese medicinal tablets with high drug loads.
Subject(s)
Zingiber officinale , Plant Extracts , Reproducibility of Results , Rhizome , Spray DryingABSTRACT
In this study, high-throughput sequencing technology was used to analyze the differentiallyexpressed microRNA (miRNA) of astrocyte-derived exosomes in control group and oxygen and glucosedeprivation/ reoxygenation (OGD/ R) group. Ultracentrifugation was used to extract exosomes from thesupernatant of astrocyte medium in the control group and OGD/ R group. Transmission electron microscopyshowed that exosomes had a typical vesicle shape with intact membrane and low electron content density. Nanoparticle tracking technology (NTA) detected astrocyte exosomes with a size of 100. 5 ± 31. 1 nm, accounting for 96. 8%. Western blot detection showed that the exosome contained exosome-specificproteins tumor-susceptibility protein (TSG101), heat shock protein 60 (Hsp60), ALG-2-interactingprotein X (ALIX). Compared with the control group, 41 miRNAs in the exosomes of the OGD / R groupwere significantly changed, of which 20 miRNAs were increased and 21 miRNAs were decreasedsignificantly (P < 0. 05). Gene ontology function (GO) analysis showed that significantly differentiallytarget genes were mainly involved in protein glycosylation, lipid metabolism, phosphorylation, Golgiapparatus, endoplasmic reticulum, endosome, cytoplasmic vesicles and cell protrusions, etc. KyotoEncyclopedia of Genes and Genomes (KEGG) pathway analysis found that differential miRNAs weremainly related to metabolic pathways and signaling pathways such as butyrate metabolism, ß-alaninemetabolism, fatty acid degradation, mitophagy and P53 signaling pathway. Sequencing analysis of theexosomal miRNAs derived from control and OGD / R astrocytes and target gene function enrichmentanalysis can be useful for the mechanism study of astrocyte exosomes in response to oxygen and glucosedeprivation reperfusion.
ABSTRACT
Objective:To prove the effect of double V-Y procedure for paramedian tubercles plasty in patients with thin lower lips and dissatisfied appearance of lower lips.Methods:From 2013 to 2019, 127 Chinese cases of thin and dissatisfied appearance of lower lips were included. A double V-Y procedure for paramedian tubercles plasty was performed. Objective data of lip morphology before and after operation were measured, and subjective satisfaction survey and long-term follow-up were conducted.Results:The midline lower red lip height, the height of paramedian tubercles of lower-lip and the protrusion of lower-lip were significantly higher than that before the operation. The time of apocatastasis, scar softening of incision, natural expression recovery and local numbness relief were evaluated by following up at 7 d, and 3-24 months after operation, and it showed 73.2% of subjective satisfaction. The time of detumescence was 6-32 (15.2±3.5) days; the time of incision scar softening was 2-10 (5.1±2.3) months; the time of expression recovery was 1-7 (3.1±0.9) months; the time of numbness disappearance was 5 d-2 years (158.2±82.6) days.Conclusions:The double V-Y advancement of vermilion mucosa flap procedure for paramedian tubercles plasty displays a significant effect in improving volume and shape of lower lips. It is recommended for further clinical application.