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Objective:To observe the role of Huaiqihuang Granules (HQ) in the long-term management of bronchial asthma in young children, and the effective effect on concomitant rhinitis.Methods:A prospective real-world multicenter study was conducted in children aged 2-5 years with asthma diagnosed in the outpatient department (from April 2016 to March 2019)who received either inhaled corticosteroid (ICS)/leukotriene receptor antagonist (LTRA)(control group); inhaled ICS/LTRA plus HQ(combination group), or HQ alone(HQ group). All patients were followed up at week 4, 8, 12 after treatment. The number of days with asthma symptoms, the frequency of severe asthma attacks, the level of asthma control, and the days with rhinitis symptoms in the last 4 weeks were recorded. Differences before and after treatment, and those among groups after treatment were compared using Kruskal- Wallis H test or Wilcoxon rank-sum test. Results:A total of 2 234 eligible patients were recruited, and 2 147 cases completed followed-up visits, including 477, 1 374 and 296 cases in the control group, combination group, and HQ group, respectively. After the treatment, all 3 groups showed significant declines in the days with asthma symptoms, frequency of severe asthma attack and the days with rhinitis symptoms (all P<0.01), and the rate of well-controlled asthma increased significantly ( P<0.01). It lasted until the end of follow-up. Among groups, patients in the combination group showed significantly less days of asthma symptoms than those of the other 2 group at week 8 and 12[0(0, 0.9) d vs.0(0, 0.3) d, P<0.05; 0(0, 0.1) d vs. 0(0, 1.0) d, P<0.01]. Patients in the combination group and HQ group showed a significantly lower rate of severe asthma attacks than that of the control group at week 12 [0(0, 1), 0(0, 1), 0(0, 2), all P<0.05]. The well-controlled rate of asthma in the combination group was significantly higher than that of the control group and HQ group at week 8 and 12 (89.6% vs. 85.9% vs.82.1%, H=15.28; 90.9% vs. 84.1% vs. 81.8%, χ2=29.32, all P<0.01). Conclusions:HQ can significantly alleviate symptoms of asthma and rhinitis, severe attack of asthma, and increase the control rate of asthma when used as an additional treatment or used alone.
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The quality of colonoscopy diagnosis and treatment is closely related to bowel cleansing. At present, polyethylene glycol electrolyte powder is the most widely used bowel cleaning regimen at home and abroad, but its intake is large, which reduces the compliance of patients. In recent years, many reports on the application of new bowel cleansing have emerged abroad. In contrast, the application of bowel cleanser in China is still relatively single, which has large room for improvement. At present, we need to solve the problem of developing a new bowel cleanser suitable for Chinese people to improve patient tolerance and bowel cleaning effect.
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【Objective】 To investigate the possible molecular pathogenesis of a child with hemophilia A accompanied by coagulation factor Ⅺ reduction by testing coagulation-related indicators and genotyping in the child and his family. 【Methods】 Peripheral blood from the patient and his parents for detection of coagulation factors Ⅷ, Ⅸ, Ⅺ, Ⅻ, VWF∶Ag, lupus anticoagulants and F VIII, F XI inhibitors were collected. All exons and flanking sequences of the genes encoding FⅧ and FⅪ were sequenced and bioinformatically analyzed. 【Results】 The child had low FⅧ and FⅪ activity and no parental abnormalities were observed. The sequencing results showed that there was a c. 1834(exon12) C>T heterozygous mutation in the FⅧ gene and a c. 1817 (exon15) G>A heterozygous mutation in the FⅪ gene, which was de novo. Bioinformatics analysis shows that the FⅪ mutation changes the original protein structure and increases the number of carboxyl groups. 【Conclusion】 For patients with prolonged APTT, in addition to excluding factors that interfere with APTT testing, all coagulation factors related to APTT should be tested to clarify the diagnosis.
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Objective To investigate the dietary intake of preschool children in Northwest China, and provide scientific basis for studying the dietary patterns and characteristics of preschool children and formulating targeted dietary interventions. Methods Using the self-designed “Semi-quantitative Food Frequency Questionnaire for Preschool Children in Northwest China“, a convenient sampling method was used to investigate the dietary intake of children aged 3 to 7 years in Northwest China. The factor analysis combined with the cluster method was used to extract the dietary pattern. Results Through factor analysis of the average daily food intake of preschool children, the results show that the KMO test value was 0.82, Bartlett’s test value was 4 528.97, and the associated probability was <0.001, so factor analysis can be performed. In order to obtain more typical factor components so that the results were easier to explain, under the guidance of nutrition experts, the first 4 common factors were finally retained for analysis, and the cumulative variance contribution rate was 62.17%. On this basis, the number of clusters was 4, and the K-means cluster analysis method was used to cluster the factor scores of various foods for preschool children. According to the proportions of various foods and the characteristics of the foods, The dietary patterns of preschool children can be divided into staple food-based dietary patterns, high-protein dietary patterns, healthy dietary patterns, and high-sugar dietary patterns. Conclusion Using factor analysis method, the scores of each food factor of preschool children were continuous variables, and the results were highly repeatable, and subsequent analysis can be carried out. The factor analysis combined with cluster analysis method extracting the dietary pattern of preschool children that had certain degree of science. According to the characteristics of the four dietary patterns extracted in this study, children's dietary interventions can be targeted to promote children's physical and mental health.
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Objective:To evaluate the effect of propofol on the sensitivity of glioma cells to temozolomide and the role of long noncoding RNAs (lncRNAs)-growth arrest-specific transcript 5 (GAS5) in it.Methods:Human glioma cell line U251 were cultured in vitro and seeded in 6-, 24- or 96-well plates at a density of 1×10 5 cells/ml, and were divided into 5 groups ( n=30 each) using a random number table method: control group (group C), temozolomide group (group T), propofol + temozolomide group (group PT), negative-siRNA + propofol + temozolomide group (group NPT) and GAS5-siRNA + propofol + temozolomide group (group GPT). The U251 cells in group C were cultured in the common culture medium.In group T, temozolomide 400 μmol/L was added to the culture medium.In group PT, the cells were cultured with propofol 8 μg/ml first and then with temozolomide 400 μmol/L.In group NPT and group GPT, U251 cells were transfected with negative-siRNA and GAS5-siRNA, respectively, and then cultured in the same way as previously described in group PT.The expression of lncRNA-GAS5 in U251 cells was detected by quantitative real-time polymerase chain reaction, the cell survival rate was measured by CCK-8 assay, the apoptosis rate was determined by flow cytometry, cell invasion was determined by Transwell invasion assay, and the expression of c-Myc, glutathione S-transferase mu 3 (GSTM3) and P21 was detected by Western blot. Results:Compared with group C, the cell survival rate was significantly decreased, the apoptosis rate was increased, the number of invasive cells was decreased, the expression of c-Myc and GSTM3 was down-regulated, and the expression of P21 and lncRNA-GAS5 was up-regulated in the other four groups ( P<0.05). Compared with group T, the cell survival rate was significantly decreased, the apoptosis rate was increased, the number of invasive cells was decreased, the expression of c-Myc and GSTM3 was down-regulated, and the expression of P21 and lncRNA-GAS5 was up-regulated in group PT and group NPT ( P<0.05). Compared with group PT, the cell survival rate was significantly increased, the apoptosis rate was decreased, the number of invasive cells was increased, the expression of c-Myc and GSTM3 was up-regulated, and the expression of P21 and lncRNA-GAS5 was down-regulated in group GPT ( P<0.05), and no significant change was found in the parameters mentioned above in group NPT ( P>0.05). Conclusions:Propofol can enhance the sensitivity of glioma cells to temozolomide, and the expression of lncRNA-GAS5 is involved in the process.
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Objective:To investigate the clinical features, diagnosis, treatment and prognosis of gastrointestinal neurilemmoma.Methods:A descriptive study was conducted to retrospectively analyze the clinical manifestations, endoscopic findings, pathological features, treatment methods and prognosis of patients with gastrointestinal neurilemmima diagnosed from May 2017 to November 2020 in the Second Affiliated Hospital of Xi'an Jiaotong UniversityResults:A total of 19 patients were collected, ranging in age from 45.0 to 70.0 years old, of whom 68.4% (13/19) were female. The clinical symptoms are non-specific, and some patients are asymptomatic (15.8%(3/19)) and may present with abdominal pain (57.9%(11/19)), nausea (31.6%(6/19)), abdominal distension (21.1%(4/19)) and decreased appetite (21.1%(4/19)), and a few with gastrointestinal bleeding (5.3%(1/19)). Tumors were most frequently found in the gastric body (42.1%(8/19)), followed by the duodenum (15.8%(3/19)). Endoscopic submucosal mass is easy to be misdiagnosed as stromal tumor. The pathological type showed shuttle cell tumor, immunohistochemical staining showed positive S100 and Vim, most Ki-67 staining proliferation rate was <5% (57.9%(11/19)), and a small part was ≥10% (10.5%(2/19)). Treatment was either endoscopic or surgical. No tendency to recur and metastasize was found in any of the neurilemmimas.Conclusion:Gastrointestinal neurilemmoma is a very rare submucosal tumor of the digestive tract, most of which are benign and rare in malignancy, and postoperative pathology is the gold standard for its diagnosis. Gastrointestinal neurilemmoma is common in middle-aged female, with diverse and non-specific clinical symptoms, difficult to differentiate from submucosal tumors such as stromal tumors, and its tendency to malignant transformation increases with tumor enlargement. Endoscopic resection is recommended for tumors with tumor diameter <3 cm without serosal invasion, with little trauma and no recurrence.
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OBJECTIVE@#Psoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61 (Cyr61), is important in its pathophysiology. Long-term clinical practice has shown that Sancao Formula (SC), a Chinese herbal compound, is effective in the treatment of psoriasis, but the precise mechanism remains unknown. In this study, we investigate the mechanism by which SC extract alleviates imiquimod (IMQ)-induced psoriasis.@*METHODS@#The expression of Cyr61 in psoriatic lesions and normal healthy skin was detected using immunohistochemical analysis to investigate the biological role of Cyr61 in models of psoriatic inflammation. A psoriatic mouse model was established by topical application of IMQ, and the effect of topical application of SC extract was evaluated using the psoriasis area and severity index (PASI) score, hematoxylin-eosin staining, and histopathological features of the skin. Next, a HaCaT cell inflammation model was established using interferon-γ (IFN-γ), and the effect of SC extract on the mRNA and protein levels of Cyr61 and intercellular cell adhesion molecule-1 (ICAM-1) was confirmed using Western blot and quantitative real-time polymerase chain reaction analyses.@*RESULTS@#Immunohistochemical staining showed that the expression of Cyr61 in psoriatic lesions was higher than that in normal skin samples (78.26% vs 41.18%, P < 0.05), and the number of Cyr61-positive cells in psoriatic lesions was also significantly higher than in normal skin (18.66 ± 2.51 vs 4.33 ± 1.52, P < 0.05). Treatment in mice with IMQ-induced psoriasis showed that SC extract could significantly improve the inflammatory phenotype, PASI score (10.875 ± 0.744 vs 3.875 ± 0.582, P < 0.05), and pathological features compared with those in IMQ model group; SC treatment was also associated with decreased levels of Cyr61 and ICAM-1. In the IFN-γ-induced inflammatory cell model, the mRNA and protein levels of Cyr61 and ICAM-1 were upregulated, while the SC extract downregulated the levels of Cyr61 and ICAM-1.@*CONCLUSION@#The results provide a theoretical basis for the involvement of Cyr61 in the pathogenesis of psoriasis, and suggest that SC should be used to target Cyr61 for the prevention of psoriasis recurrence.
Subject(s)
Animals , Mice , China , Cysteine-Rich Protein 61/metabolism , Disease Models, Animal , Drugs, Chinese Herbal/therapeutic use , Imiquimod/adverse effects , Inflammation/drug therapy , Intercellular Adhesion Molecule-1/genetics , Interferon-gamma , Mice, Inbred BALB C , Psoriasis/pathology , RNA, Messenger/therapeutic useABSTRACT
OBJECTIVES@#To investigate the growth and development of children aged 0-6 years in Jiangsu Province of China and the effects of family factors on the children's growth and development.@*METHODS@#The stratified random sampling method was used to select 2 004 families with children aged 0-6 years of Jiangsu Province. A questionnaire survey on nutritional knowledge, attitude, and behavior was performed for the main caregivers. The Z-score method was used to evaluate nutritional status. The ordinal polytomous logistic regression analysis model was used to investigate the influencing factors for nutritional status.@*RESULTS@#A total of 2 290 questionnaires were distributed, among which 2 004 valid questionnaires were collected (87.51%). The mean age of the children was (28±14) months, and there were 1 105 boys (55.14%) and 899 girls (44.86%). The primary caregivers were mostly parents (1 867 families, 93.16%), and the caregivers of 1 466 families (73.15%) had a university/college degree. Most families had an annual income of 50 000-100 000 yuan/year or 100 000-200 000 yuan/year, accounting for 32.88% and 34.23%, respectively. The results of Z-score showed the growth retardation rates of 1.45% (16/1 105) in boys and 1.78% (16/899) in girls, the underweight rates of 0.54% (6/1 105) in boys and 0.67% (6/899) in girls, the emaciation rates of 1.36% (15/1 105) in boys and 2.00% (18/899) in girls, and the obesity rates of 8.78% (97/1 105) in boys and 10.12% (91/899) in girls, respectively. The multivariate logistic regression analysis showed that a higher annual family income and a higher nutrition knowledge level of caregiver were beneficial to the growth and development of children (P<0.05).@*CONCLUSIONS@#Children aged 0-6 years in Jiangsu Province have a good status of growth and development but a relatively high obesity rate, and therefore, the monitoring of obesity should be taken seriously. Family economic status and the level of nutritional knowledge of caregivers have a significant impact on children's growth and development.
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Child , Child, Preschool , Female , Humans , Infant , Male , Body Weight , China/epidemiology , Cross-Sectional Studies , Nutritional Status , ObesityABSTRACT
With the widespread application of genomics and transcriptomics in the genetics and cell biology of different species, synonymous codon usage bias has been gradually accepted and used to study the deep connection between biological evolution and biological phenotypes. It is an important part of the life activities that mRNA is expressed into proteins with normal biological activities. The synonymous codon usage patterns, which were named as 'the second genetic codon', can express genetic information carried by themselves at the levels of transcriptional regulations, translational regulations and metabolic activities through molecular mechanisms such as fine-tune translation selection. Some studies have shown that the length of mRNA half-life has significant impacts on mRNA activity and the process of transcription and translation. This review summarized the roles of synonymous codon usage patterns in transcription, translational regulation and post-translational modification, with the aim to better understand how organisms skillfully utilize the genetic effects caused by codon usage patterns to accurately synthesize different types of proteins, so as to ensure the growth or differentiation of the specific gene expression procedures to carry out smoothly and maintain the normal life cycle.
Subject(s)
Codon/genetics , Codon Usage , Half-Life , Protein Processing, Post-Translational , RNA, Messenger/geneticsABSTRACT
Hemophilia is a hereditary bleeding disorder where the only effective treatment is factor replacement therapy. The main contradiction of hemophilia in China is the contradiction between the increasing demand for quality of life of hemophilia patients and insufficient medical insurance, medical treatment and medicine. Expensive treatment costs are the main reason for patients to "be impoverished due to illness" and "return to poverty due to illness". This article analyzes the current status of the hemophilia aid system through the existing literature data and existing patient aid projects. Cooperation of social insurance, social relief and high-quality medical services is critical to a complete hemophilia comprehensive medical aid system, so that hemophilia patients can receive standardized diagnosis and treatment, and try to achieve the close quality of life as normal.
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As the main cell type in mammalian cortex, cortical projection neurons play an important role in brain functions, including motor control, sensation and cognition.Projection neurons in the cerebral cortex include excitatory projection neurons and inhibitory projection neurons, of which excitatory projection neurons are the main type.Cortical excitatory projection neurons have various subtypes, and most of them have their own unique developmental rules and molecular markers.Studying the origin and classification of projection neurons in the cerebral cortex is helpful to understand the mechanisms of diseases related to abnormal projection neurons.This paper reviews the origin, classification and function of cortical projection neurons.
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Sexual dysfunction with the incidence of 5%-90% is a common postoperative complication of rectal cancer and the ratio of men and women is similar. Sexual function is innervated by the abdominal-pelvic autonomic nerve. Different sexual dysfunctions can be caused by different parts and degrees of injury in autonomic nerve during operations of rectal cancer. With the development of pelvic autonomic nerves preservation in rectal cancer radical resection, postoperative sexual function can be protected. There may be many factors increasing the incidence of postoperative sexual dysfunction in rectal cancer, such as postoperative psychological factors, stoma, abdominal-perineal resection and radiotherapy. The effects of laparoscopic surgery, robotic surgery, transanal total mesorectal excision and lateral lymph node dissection on postoperative sexual function remain controversial. Based on the multidisciplinary cooperation model, attention should be paid to psychological intervention of patients and their partners. In clinical practice, for male using phosphodiesterase-5 inhibitors, vacuum erectile devices, injection of vasodilators through the penis or urethra, and for female local application of estrogen and lubricants in the vagina are effective treatment for postoperative sexual dysfunction of rectal cancer. In addition, stem cell therapy has a promising prospect for sexual dysfunction.
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Female , Humans , Male , Laparoscopy , Lymph Node Excision , Rectal Neoplasms/surgery , Rectum/surgery , Sexual Dysfunction, Physiological/etiologyABSTRACT
Tropheryma whipplei (TW) is an opportunistic pathogen that can cause Whipple′s disease (WD). Recently, the biomedical field is concerned about whether the bacteria cause pneumonia. When BALF was detected by PCR, the TW positive rate was about 6.1%. Etiology status is generally described as “associated” or “probable”. Immunocompromised status is the susceptible factor; Different species of the same genus have been reported. The current method may have missed detection. All relevant information needs further study. This article reviews the acute pneumonia caused by TW and the detection technology.
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@#AIM: To explore the mechanism of rejection of bioengineered keratoplasty by the laser confocal microscope and immunopathological studies.<p>METHODS: Retrospective case study. Five patients(5 eyes)who underwent bioengineered keratoplasty for infectious keratitis from Sep.2018 to Dec.2020 and were immunologically rejected included. All observers were monocular. Slit-lamp was used to examine corneal transparency and corneal neovascularization. The cornea was dynamically observed under laser confocal microscopy, the density of subepithelial langerhans cells and stromal inflammatory cells was recorded after graft rejection, and the contralateral eye was used as the control group for statistical analysis. The infiltration and distribution of CD4<sup>+</sup> cells, CD8<sup>+</sup> cells and inflammatory cells were observed after immunohistochemical staining of bioengineered corneas during corneal allograft.<p>RESULTS: Confocal laser microscopy showed that a large number of langerhans cells were activated under the corneal epithelium of the intraoperative eye, and the activation ratio was significantly different from that of the contralateral eye(χ<sup>2</sup>=38.29, <i>P</i><0.001). The stromal layer was rich in inflammatory cells, which was significantly different from that of the contralateral eye(<i>t</i>=32.5, <i>P</i><0.05). Immunohistochemical staining and HE staining were performed on the bioengineering corneal tissue. CD4<sup>+</sup> and CD8<sup>+</sup> cells were observed in all corneal stromal layers, and only one case had a large number of eosinophils.<p>CONCLUSION: Immunopathology of rejection after bioengineered keratoplasty confirmed that T-cell-mediated cellular immunity plays an important role in the pathogenesis, and hypersensitivity to xenoantigen may be involved in it.
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Objective:To observe the influence of SBAR communication mode on the condition of patients undergoing thoracolaparoscopic combined with esophageal cancer resection.Methods:A total of 200 patients who were admitted to the Department of Gastroenterology and Oncology from October 2017 to October 2019 in Affiliated Hospital of Southwest Medical University were selected for elective thoracolaparoscopic combined with esophageal cancer resection. According to the random number method, they were divided into 100 cases in the control group and the SBAR group. The control group used conventional preoperative communication visit mode, and the SBAR group used SBAR communication mode and preoperative visit based on the control group. The following items such as the preoperative negative mentality scores, quality of life score, postoperative complications and nursing satisfaction rate of the two groups before and after nursing interventionwere compared.Results:Before the intervention, the difference of the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) scores of the two groups was not statistically significant ( P>0.05). After the intervention, the SAS and SDS scores of the two groups were 49.32±4.96, 55.95±5.32, 50.93±4.74, and 56.33±5.89, respectively, which were significantly reduced. The SDS and SAS scores of the SBAR group were lower than those of the control group ( t values were -9.115 and -7.142, P<0.001). The difference of the World Health Organization Brief Table on Quality of Life (WHOQOL-BREF) scores of the two groups before the intervention was not statistically significant ( P>0.05). After the intervention, the WHOQOL-BREF scores of the two groups were 12.27±1.39 vs. 9.18±1.24, 16.13±1.51 vs. 12.48±1.22, 16.13±1.95 vs. 12.71±1.28, 15.09±1.81 vs. 13.08±1.48, 18.11±1.82 vs. 13.51±1.47, 14.09±1.61 vs. 12.98±1.28. The scores of the SBAR group were higher than those of the control group ( t values were 5.397-19.662, P<0.001). The postoperative complications rate of the SBAR group was 3.00% (3/100), which was less than 18.00% (18/100) of the control group ( χ 2 value was 11.971, P<0.001). The overall satisfaction rate of patients in the SBAR group with care was 100.00% (100/100), which was higher than the 84.00% (100/100) in the control group ( χ 2 value was 17.391, P<0.001). Conclusions:In patients with esophageal cancer undergoing thoracic laparoscopy combined with esophageal cancer resection, the use of SBAR communication mode for the patient′s preoperative visit can significantly reduce the patient′s preoperative anxiety and depression negative scores and improve the patient′s quality of life, reduce the occurrence of postoperative complications, improve patient satisfaction with nursing with ideal effect.
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Due to the complicated anatomical structures in the furcation area of multirooted mandibular first molars, dental hygiene is greatly compromised once the furcation is involved in the periodontitis, leading to the unfavorable prognosis of teeth with furcation involvement. A patient came to a dental office with the chief complaint of "mobile mandibular posterior tooth" 27 years ago. The periapical film showed alveolar bone resorption at the root furcation of the right mandibular first molar. Flap surgery and fine supportive therapy were conducted. The patient was diagnosed with "furcation involvement Class Ⅲ" during a revisit three years ago. Satisfactory and healthy periodontal statuses were observed 2, 9, 24, and 33 months after the periodontal flap surgery plus tunneling procedures. A follow-up of 27 years in the present case demonstrated that a favorable prognosis of furcation involvement can be achieved after adequate periodontal treatment.
Subject(s)
Humans , Follow-Up Studies , Furcation Defects/surgery , Mandible , Molar , PeriodontitisABSTRACT
OBJECTIVE@#To detect and analyze coagulation related indexes and genotypes of a patient with congenital fibrinogen deficiency and his family members, and to investigate the possible molecular pathogenesis.@*METHODS@#Four peripheral blood samples (proband and 3 family members) were collected and the prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fg), D-Dimer and eight coagulation factor indicators were detected. All exons and flanking sequences of the FGA, FGB, and FGG genes encoding the three peptide chains of fibrinogen were sequenced and analyzed by bioinformatics.@*RESULTS@#Among the eight coagulation factors of the proband and the elder sister, F Ⅴ and F Ⅷ were slightly higher, TT was significantly prolonged, and Fg was significantly reduced. Sequencing results showed that c.901C>T heterozygous mutation existed in the FGG gene. Bioinformatics analysis showed that the mutation changed the original protein structure and reduced the number of hydrogen bonds.@*CONCLUSION@#The fibrinogen gamma chain c.901C>T heterozygous mutation is the main cause of congenital fibrinogen deficiency in this family. This mutation is reported for the first time at home and abroad.
Subject(s)
Aged , Humans , Afibrinogenemia/genetics , Fibrinogen/genetics , Heterozygote , Mutation , PedigreeABSTRACT
Collagen α3 (IV) chains are one of the major constituent components of the basement membrane in the mammalian testis. Studies have shown that biologically active fragments, such as noncollagenase domain (NC1)-peptide, can be released from the C-terminal region of collagen α3 (IV) chains, possibly through the proteolytic action of metalloproteinase 9 (MMP9). NC1-peptide was shown to promote blood-testis barrier (BTB) remodeling and fully developed spermatid (e.g., sperm) release from the seminiferous epithelium because this bioactive peptide was capable of perturbing the organization of both actin- and microtubule (MT)-based cytoskeletons at the Sertoli cell-cell and also Sertoli-spermatid interface, the ultrastructure known as the basal ectoplasmic specialization (ES) and apical ES, respectively. More importantly, recent studies have shown that this NC1-peptide-induced effects on cytoskeletal organization in the testis are mediated through an activation of mammalian target of rapamycin complex 1/ribosomal protein S6/transforming retrovirus Akt1/2 protein (mTORC1/rpS6/Akt1/2) signaling cascade, involving an activation of cell division control protein 42 homolog (Cdc42) GTPase, but not Ras homolog family member A GTPase (RhoA), and the participation of end-binding protein 1 (EB1), a microtubule plus (+) end tracking protein (+TIP), downstream. Herein, we critically evaluate these findings, providing a critical discussion by which the basement membrane modulates spermatogenesis through one of its locally generated regulatory peptides in the testis.
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Objective:To explore the potential molecular mechanism of Nelumbinis Plumula alkaloids （NAPs） in the prevention and treatment of non-small cell lung cancer （NSCLC） based on network pharmacology and cell experiment. Method:The main active components of NAPs were obtained by searching Traditional Chinese Medicine System Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）， and their main targets were predicted and analyzed by employing Swiss Target Prediction. The main target genes of NSCLC were retrieved from GeneCards， Online Mendelian Inheritance in Man （OMIM） and DrugBank databases. The resulting common targets were imported into STRING platform for constructing the protein-protein interaction （PPI） network， followed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis based on Database for Annotation， Visualization， and Integrated Discovery （DAVID）. The NAPs-common target -pathway network was constructed by Cytoscape 3.7.1. After NSCLC cell line A549 was treated with isoliensinine， the cell morphology was observed under an inverted fluorescence microscope. The effect of isoliensinine on A549 vitality was detected by cell counting kit-8 （CCK-8） assay and the target protein changes were verified by Western blot. Result:The main active components for NAPs against NSCLC were lysicamine， liensinine， and isoliensinine. The phosphatidylinositol-3-kinase-protein kinase B （PI3K-AKT）， RAS-related protein 1 （Rap1）， epidermal growth factor family of receptor tyrosine kinases （ErbBs）， and hypoxia inducible factor-1 （HIF-1） pathways were mainly involved for binding adenosine triphosphate （ATP） and regulating protein kinase activity. The main targets included protein kinase B-1 （AKT1）， alpha catalytic subunit of phosphoinositol-3-kinase （PIK3CA）， cyclin-dependent kinase 2 （CDK2）， mitogen-activated protein kinase-1 （MAPK1）， epidermal growth factor receptor （EGFR）， adenosine triphosphate-binding cassette B1 （ABCB1）， mammalian target of rapamycin （mTOR）， tyrosine kinase （Src）， Janus kinase 1 （JAK1）， and G1-phase-specific gene cyclin-D<sub>1</sub> （CCND1）. The <italic>in vitro</italic> cell experiment also revealed that isoliensinine down-regulated the expression of phosphorylated AKT （p-AKT） and phosphorylated mTOR （p-mTOR） in a concentration- and time-dependent manner and inhibited the growth of A549 cells. Conclusion:NAPs exert the preventive and therapeutic effects against NSCLC through multiple components， multiple targets， and multiple pathways， especially the PI3K-AKT pathway.
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According to human carboxylesterase 2(hCE2) inhibitors reported in the literature, the pharmacophore model of hCE2 inhibitors was developed using HipHop module in Discovery Studio 2016. The optimized pharmacophore model, which was validated by test set, contained two hydrophobic, one hydrogen bond acceptor, and one aromatic ring features. Using the pharmacophore model established, 5 potential hCE2 inhibitors(CS-1,CS-2,CS-3,CS-6 and CS-8) were screened from 20 compounds isolated from the roots of Paeonia lactiflora, which were further confirmed in vitro, with the IC_(50) values of 5.04, 5.21, 5.95, 6.64 and 7.94 μmol·L~(-1), respectively. The results demonstrated that the pharmacophore model exerted excellent forecasting ability with high precision, which could be applied to screen novel hCE2 inhibitors from Chinese medicinal materials.