Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

OBJECTIVE To investigate the effect and mechanism of action of KRT8 small interfering RNA(si-KRT8)in exosomes derived from patient serum with hypopharyngeal carcinoma on chemosensitivity to 5-fluorouracil(5-FU)in human pharyngeal squamous cell carcinoma FaDu cell line.METHODS The cancerous tissues of hypopharyngeal cancer patients and The serum,cancerous tissues and paracancerous tissues of drug-resistant patients after treatment were collected.A 5-FU-resistant cell line of FaDu(FaDu/R)was constructed for subsequent experiments.Exosomes were isolated from patient serum by ultrafast gradient centrifugation,identified using transmission electron microscopy and Western blot(WB)techniques.si-KRT8 was encapsulated into exosomes(Exosome@si-KRT8)using electroporation technology and subsequently used to treat cells.Real-time fluorescence quantitative PCR(RT-qPCR)and WB were used to detect the expression levels of KRT8 in different tissues,exosomes after electroporation of si-KRT8,and FaDu cells,respectively.Cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay,migration invasion technique and WB were used to detect the effects of Exosome@si-KRT8 on viability,apoptosis,and epithelial-mesenchymal transition of FaDu/R cells.RESULTS The expression level of KRT8 in drug-resistant tissues of hypopharyngeal carcinoma and FaDu/R cells was elevated compared with that in paraneoplastic tissues,cancer tissues and normal FaDu cells(t=15.79,P＜0.01).Isolated patient serum exosomes showed a double membrane structure and expressed both CD63 and TSG101 proteins,and KRT8 expression in exosomes was decreased after electro-transfection with si-KRT8(t=6.70,P＜0.01).Exosome@si-KRT8 inhibited KRT8 protein expression levels in FaDu/R cells(t=123.50,P＜0.01).Compared with the 5-FU group and the 5-FU+Exosome group,Exosome@si-KRT8 was able to inhibit the viability of FaDu/R cells(t=17.07,P＜0.01),promote the level of apoptosis in FaDu/R cells,and inhibit the expression of drug-resistance-associated proteins in FaDu/R cells(P-gp:t=103.20,MDR1:t=238.60,P＜0.01),and Exosome@si-KRT8 was able to suppress the expression of metastasis of FaDu/R cells(t=42.30,t=122.00,P＜0.01)and promoted the expression of E-cadherin while inhibiting the expression level of N-cadherin(t=130.80,t=83.90,P＜0.01).CONCLUSION Serum-derived exosome encapsulation of si-KRT8 enhances chemosensitivity of hypopharyngeal carcinoma cells and its mechanism of action may be related to inhibition of epithelial-mesenchymal transition.

Objective: In order to elucidate the biological activity of the co-cultured adventitious roots (ARs) of Echinacea pallida and Echinacea purpurea and provide theoretical basis for its application, and the anti-inflammatory activities and potential mechanisms of co-cultured ARs were studied. Methods: The experimental materials were obtained by bioreactor co-culture technology and used in the activity research. In this study, mouse macrophages induced by lipopolysaccharide (LPS) were used as in vitro model. Different concentrations of AR extract (50–400 g/mL) were used to treat cells. The expression of pro-inflammatory cytokines was determined using enzyme linked immunosorbent assay. The inducible nitric oxide synthase and cyclooxygenase-2 expression, mitogen-activated protein kinase (MAPK) phosphorylation, and the inhibitor of nuclear factor-kappa B-α levels were determined by the Western blot analysis. Results: In the co-cultured ARs, total flavonoids and total caffeic acid were determined, and the contents of both bioactive compounds were significantly higher than those ARs from the single-species culture. Compared with the control group, the large amount of pro-inflammatory mediators was released after LPS stimulation. However, in the extract groups with different concentrations (25, 50, and 100 g/mL), the production of these pro-inflammatory mediators was inhibited in a dose-dependent manner. Furthermore, the levels of phosphorylation of MAPK proteins, including p-p38, p-c-Jun N-terminal kinase, and p-extracellular regulated protein kinases were significantly (P < 0.05) decreased in the extract groups, revealing that the AR extract probably involved in regulating the MAPK signaling pathway. Conclusion: Collectively, our findings suggested that the co-cultured ARs of E. pallida and E. purpurea can inhibit production of pro-inflammatory mediators in mouse peritoneal macrophages and possess the anti-inflammatory effect by regulating MAPK signaling pathways.

OBJECTIVE: To study whether there are differences in the resuscitation process and early outcomes between the extremely preterm infants delivered on off-hours (6 pm to 8 am of working days, weekends, and national holidays) and those delivered on working hours. METHODS: A retrospective analysis was performed on the medical data of extremely preterm infants who were born in the Peking University Third Hospital from January 1, 2010 to December 31, 2020 and transferred to the neonatal intensive care unit (NICU). According to the time of birth, they were divided into two groups:working hours ( RESULTS: Compared with the working hours group, the off-hours group had a significantly lower proportion of infants with the use of full-dose dexamethasone before delivery ( CONCLUSIONS Extremely preterm infants delivered on off-hours tend to have a low Apgar score at 1 minute after birth, with a higher proportion of infants requiring positive pressure ventilation or tracheal intubation during resuscitation than those delivered on working hours, and they tend to develop neonatal respiratory distress syndrome and intrauterine pneumonia. This suggests that it is important to make adequate preparations in terms of personnel and supplies for resuscitation of extremely preterm infants after birth and that NICUs should develop a detailed management plan for extremely preterm infants at each period of time before, during, and after birth.
Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Intensive Care Units, Neonatal ; Respiratory Distress Syndrome, Newborn ; Resuscitation ; Retrospective Studies

OBJECTIVE: To analyze the distribution and pathogenicity of 27 HPV(Human papillomavirus)subtypes in cervical lesions.METHODS: A retrospective analysis was carried out in 5735 patients with cervical lesions admitted to the First Affiliated Hospital of Wenzhou Medical University from January 2015 to July 2017,including 997 cases of cervicitis,1568 cases of LSIL(low-grade squamous intraepithelial lesion),2576 cases of HSIL(high-grade squamous intraepithelial lesion)and 594 cases of cervical cancer. The HPV subtypes,histopathological results and ages were obtained for analysis.RESULTS: The positive rates of HPV in cervicitis group,LSIL,HSIL group and cervical cancer group were 57.0%,78.3%,90.5%,and 93.9%(P<0.05)respectively. The five most prevalent HPV types in cervicitis and LSIL group were 52,53,16,58 and 18;in HSIL and cervical cancer they were 16,52,58,33 and 18. The cumulative attribution rates of HPV16,18,58,52,33,31 and 45 in cervicitis,LSIL,HSIL and cervical cancer were 22.2%,38.4%,68.4% and 80.1%,respectively. The incidence of cervical cancer after HPV16,31 and 45 infection was 27.7,14.3 and8.2 times higher than that of cervicitis. Among the 36 cervical cancer tissue samples with negative HPV,8 cases were detected positive by HPV E6/E7 DNA detection.CONCLUSION: HPV16,18,58,52,33,31 and 45 have a high prevalence,cumulative attribution rates and risk values in patients with squamous intraepithelial lesions and cervical cancer. The above-mentioned subtypes of HPV should be included in the prevention and screening of cervical cancer.HPV E6/E7 DNA detection may be a reliable assay for HPV-based screening for prevention of cervical cancer.

OBJECTIVE: To investigate the physical development, incidence of common respiratory diseases, and motor development during infancy in preterm infants with bronchopulmonary dysplasia (BPD). METHODS: A retrospective analysis was performed on the clinical features and infantile outcomes of preterm infants with BPD who were admitted to the neonatal intensive care unit between January 2012 and December 2015. Preterm infants without BPD were used as controls who were admitted to the neonatal intensive care unit during the same period and had similar gestational age and birth weight. Physical development, number of hospital stays, the incidences of pneumonia and wheezing, and motor development during infancy were compared between the two groups. RESULTS: Compared with the control group, BPD infants had a significantly higher incidence of extrauterine growth retardation at discharge (48% vs 41%; P<0.05); BPD infants were more susceptible to pneumonia, wheezing, eczema and rhinitis; BDP infants also had a significantly higher number of readmissions due to respiratory tract infection (P<0.05). BPD infants had a significantly smaller head circumference than the control group at corrected ages of 3, 6, and 12 months (P<0.05). BPD infants had significantly delayed gross, fine, and overall motor development than the control group at corrected ages of 6 and 9 months (P<0.05). CONCLUSIONS Infants with BPD are susceptible to extrauterine growth retardation at discharge. Their head circumference growth is relatively slow. They are susceptible to pneumonia and wheezing during infancy. Moreover, they have delayed motor development when compared with those without BPD at corrected ages of 6 and 9 months.
Bronchopulmonary Dysplasia ; Child ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Prognosis ; Retrospective Studies

A boy aged 2 months (born at 36 weeks of gestation) was admitted due to cough and dyspnea. After admission, he was found to have persistent hypertension, proteinuria, and persistent convulsion, and imaging examination showed extensive calcification of the aorta and major branches and stenosis of local lumens of the abdominal aorta and the right renal artery with increased blood flow velocity. The boy was admitted during the neonatal period due to wet lung and pulmonary arterial hypertension and was found to have hypertension and proteinuria. High-throughput whole-exome sequencing was performed and found two compound heterozygous mutations in the ENPP1 gene from his parents, c.130C>T (p.Q44X) and c.1112A>T (p.Y371F). c.130C>T was a nonsense mutation, which could cause partial deletion of protein from 44 amino acids, and was defined as a primary pathogenic mutation. c.1112A>T was a missense mutation which had been reported as a pathogenic mutation associated with idiopathic infantile arterial calcification (IIAC). Therefore, he was diagnosed with IIAC. He was given phosphonate drugs, antihypertensive drugs, anticonvulsion treatment, and respiratory support. Blood pressure was maintained at the upper limit of normal value. There was no deterioration of arterial calcification. It is concluded that IIAC should be considered for infants with persistent hypertension and extensive vascular calcification, and imaging and genetic examinations should be performed as early as possible to make a confirmed diagnosis.
Humans ; Hypertension ; Infant ; Infant, Premature ; Male ; Mutation ; Vascular Calcification

AMP-activated protein kinase (AMPK) activation has been shown to protect against fibrosis. However, the underlying mechanism remains unclear. Here we explored the effect of AMPK activation on transforming growth factor-β1 (TGFβ1) production induced by angiotensin II (AngII) in cardiac fibroblasts and the underlying mechanisms. Adult mouse cardiac fibroblasts were isolated. TGFβ1 and AMPK activity were determined by ELISA and Western blots, respectively. Pretreatment of AMPK activator AICAR inhibited TGFβ1 production induced by AngII in cardiac fibroblasts, which was reversed by AMPK inhibitor compound C. Furthermore, bioinformatics predicted a potential CCAAT/enhancer-binding protein β (C/EBPβ) binding site in the promoter region of the mouse Tgfb1 gene. Luciferase reporter with wild type, but not deleted, C/EBPβ binding sites transfection in mouse embryonic fibroblasts showed increased TGFβ1 transcriptional activity induced by AngII, indicating that C/EBPβ mediates AngII-induced TGFβ1 transcript expression. Pretreatment of AICAR inhibited C/EBPβ expression induced by AngII. In conclusion, AMPK activation inhibited TGFβ1 production induced by AngII in cardiac fibroblasts through targeting C/EBPβ. This finding provides a new mechanism underlying the anti-fibrogenic effects of AMPK activation.

OBJECTIVETo study the relationship between angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and left ventricular mass (LVM) in newborns admitted to the neonatal intensive care unit (NICU).

METHODSSeventy-two newborns admitted to the NICU were enrolled. ACE genotypes were determined by genomic DNA which was isolated from heel-prick blood. Disease status of the newborns was evaluated by the Neonatal Critical Score (draft) on postnatal day 1. LVM and LVM index (LVMI) were evaluated by echocardiography on postnatal days 1-3.

RESULTSDD genotype was identified in 11 cases, ID genotype in 31 cases, and II genotype in 30 cases. There were no significant differences in clinical characteristics, critical score and body measurements in newborns with different genotypes. The DD genotype group showed significantly lower LVMI than the group with ID+II genotypes (29±4 g/m2 vs 35±8 g/m2; P<0.05).

CONCLUSIONSACE gene polymorphism is associated with the LVMI in newborns admitted to the NICU. The LVMI of DD genotype carriers is significantly lower than that of ID+II genotypes carriers, which suggests that D allele may be associated with the growth and development of left ventricular.

Echocardiography ; Female ; Gene Deletion ; Genotype ; Heart Ventricles ; diagnostic imaging ; Humans ; Intensive Care Units, Neonatal ; Male ; Mutagenesis, Insertional ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic

Objective To explore the effect of self-control ability to disease recurrence of the patients suffered from colpitis and take effective nursing interference to reduce the disease recurrence of the patients.Methods 300 cases of the patients suffered from colpitis were divided into 150 cases as the experimental group and 150 cases as the control group randomly. The patients of the experiment group used self-control mode to execute individualization of nursing interference and the patients of the control group used normal instruction.Individuals of the two groups were treated with the same medicine. The comparison of the related factor for two groups of the patients has been made in the questionnaire, self -control ability assessment form, recurrence of long time after the treatment. Results The self-control ability of the experiment group was evidently higher than the control group and the disease recurrence rate was evidently lower. Conclusions The self-control mode was used for nursing interference may improve the self-control ability, change bad custom of the life consciously,recognize and exterminate the disease recurrence so as to reduce the disease recurrence and improve the quality of life.