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1.
Front Pharmacol ; 15: 1270612, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655179

RESUMO

Aims: Vincristine (VCR), an antineoplastic drug, induces peripheral neuropathy characterized by nerve damage, limiting its use and reducing the quality of life of patients. VCR causes myenteric neuron damage, inhibits gastrointestinal motility, and results in constipation or paralytic ileus in patients. Oxytocin (OT) is an endogenous neuropeptide produced by the enteric nerve system, which regulates gastrointestinal motility and exerts neuroprotective effects. This study aimed to investigate whether OT can improve VCR-induced gastrointestinal dysmotility and evaluate the underlying mechanism. Methods: Mice were injected either with saline or VCR (0.1 mg/kg/d, i. p.) for 14 days, and OT (0.1 mg/kg/d, i.p.) was applied 1 h before each VCR injection. Gastrointestinal transit and the contractile activity of the isolated colonic segments were assessed. The concentration of OT in plasma was measured using ELISA. Immunofluorescence staining was performed to analyze myenteric neurons and reactive oxygen species (ROS) levels. Furthermore, the indicators of oxidative stress were detected. The protein expressions of Nrf2, ERK1/2, P-ERK1/2, p38, and P-p38 in the colon were tested using Western blot. Results: VCR reduced gastrointestinal transit and the responses of isolated colonic segments to electrical field stimulation and decreased the amount of neurons. Furthermore, VCR reduced neuronal nitric oxide synthase and choline acetyltransferase immunopositive neurons in the colonic myenteric nerve plexus. VCR increased the concentration of OT in plasma. Exogenous OT pretreatment ameliorated the inhibition of gastrointestinal motility and the injury of myenteric neurons caused by VCR. OT pretreatment also prevented the decrease of superoxide dismutase activity, glutathione content, total antioxidative capacity, and Nrf2 expression, the increase of ROS levels, and the phosphorylation of ERK1/2 and p38 MAPK following VCR treatment. Conclusion: Our results suggest that OT pretreatment can protect enteric neurons from VCR-induced injury by inhibiting oxidative stress and MAPK pathways (ERK1/2, p38). This may be the underlying mechanism by which it alleviates gastrointestinal dysmotility.

2.
Biotechnol Bioeng ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548653

RESUMO

Nanobody (Nb), the smallest antibody fragments known to bind antigens, is now widely applied to various studies, including protein structure analysis, bioassay, diagnosis, and biomedicine. The traditional approach to generating specific nanobodies involves animal immunization which is time-consuming and expensive. As the understanding of the antibody repertoire accumulation, the synthetic library, which is devoid of animals, has attracted attention widely in recent years. Here, we describe a synthetic phage display library (S-Library), designed based on the systematic analysis of the next-generation sequencing (NGS) of nanobody repertoire. The library consists of a single highly conserved scaffold (IGHV3S65*01-IGHJ4*01) and complementary determining regions of constrained diversity. The S-Library containing 2.19 × 108 independent clones was constructed by the one-step assembly and rapid electro-transformation. The S-Library was screened against various targets (Nb G8, fusion protein of Nb G8 and green fluorescent protein, bovine serum albumin, ovalbumin, and acetylcholinesterase). In comparison, a naïve library (N-Library) from the source of 13 healthy animals was constructed and screened against the same targets as the S-Library. Binders were isolated from both S-Library and N-Library. The dynamic affinity was evaluated by the biolayer interferometry. The data confirms that the feature of the Nb repertoire is conducive to reducing the complexity of library design, thus allowing the S-Library to be built on conventional reagents and primers.

3.
Toxicol Appl Pharmacol ; 484: 116887, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38458354

RESUMO

AIMS: Gastrointestinal paresthesia and dysmotility are common side effects of vincristine (VCR) chemotherapy, which have become one of the factors for dose reduction, therapy delay or discontinuation. However, the mechanism is not entirely clear, whether it is related to autonomic nerves injury remains unknown. Therefore, we aimed to study whether VCR-induced gastrointestinal toxicity is related to changes in mesenteric afferent activity. METHODS: The effects of a single VCR stimulation and long-term systemic VCR treatment on mesenteric afferent activity were investigated by directly recording mesenteric afferent discharge in vitro. RESULTS: Our results showed that a single VCR (0.001-1 µmol/L) stimulation obviously increased the spontaneous, chemically evoked and mechanically evoked discharge of jejunal and colonic mesenteric afferents. This kind of hypersensitivity of VCR could be blocked by capsazepine, a transient receptor potential vanilloid 1 (TRPV1) antagonist. For the mice treated with VCR (0.1 mg/kg/d, i.p.) for 14 days, the abdominal withdrawal reflex and writhing response scores were reduced. Meanwhile, the spontaneous discharge of colonic mesenteric afferents and the afferent response to VCR was downregulated, and the afferent sensitivity to chemical and mechanical stimulation was reduced. Moreover, the expression of TRPV1 in colon was decreased. CONCLUSIONS: These results suggest that the direct stimulation by VCR increases the mesenteric afferent sensitivity by activating TRPV1, which may be the reason of VCR-induced abdominal pain; the long-term systemic treatment of VCR decreases mesenteric afferent sensitivity by reducing TRPV1, which may be the reason of VCR-induced constipation.


Assuntos
Canais de Cátion TRPV , Camundongos , Animais , Vincristina/toxicidade , Regulação para Baixo , Canais de Cátion TRPV/metabolismo
4.
Cell Death Dis ; 15(1): 27, 2024 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-38199990

RESUMO

Intestinal epithelial renewal, which depends on the proliferation and differentiation of intestinal stem cells (ISCs), is essential for epithelial homoeostasis. Understanding the mechanism controlling ISC activity is important. We found that death receptor 5 (DR5) gene deletion (DR5-/-) mice had impaired epithelial absorption and barrier function, resulting in delayed weight gain, which might be related to the general reduction of differentiated epithelial cells. In DR5-/- mice, the expression of ISC marker genes, the number of Olfm4+ ISCs, and the number of Ki67+ and BrdU+ cells in crypt were reduced. Furthermore, DR5 deletion inhibited the expression of lineage differentiation genes driving ISC differentiation into enterocytes, goblet cells, enteroendocrine cells, and Paneth cells. Therefore, DR5 gene loss may inhibit the intestinal epithelial renewal by dampening ISC activity. The ability of crypts from DR5-/- mice to form organoids decreased, and selective DR5 activation by Bioymifi promoted organoid growth and the expression of ISC and intestinal epithelial cell marker genes. Silencing of endogenous DR5 ligand TRAIL in organoids down-regulated the expression of ISC and intestinal epithelial cell marker genes. So, DR5 expressed in intestinal crypts was involved in the regulation of ISC activity. DR5 deletion in vivo or activation in organoids inhibited or enhanced the activity of Wnt, Notch, and BMP signalling through regulating the production of Paneth cell-derived ISC niche factors. DR5 gene deletion caused apoptosis and DNA damage in transit amplifying cells by inhibiting ERK1/2 activity in intestinal crypts. Inhibition of ERK1/2 with PD0325901 dampened the ISC activity and epithelial regeneration. In organoids, when Bioymifi's effect in activating ERK1/2 activity was completely blocked by PD0325901, its role in stimulating ISC activity and promoting epithelial regeneration was also eliminated. In summary, DR5 in intestinal crypts is essential for ISC activity during epithelial renewal under homoeostasis.


Assuntos
Benzamidas , Difenilamina , Ftalimidas , Receptores do Ligante Indutor de Apoptose Relacionado a TNF , Células-Tronco , Tiazolidinas , Animais , Camundongos , Difenilamina/análogos & derivados , Homeostase
5.
Food Funct ; 15(2): 625-646, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38099724

RESUMO

Delayed mucosal healing and impaired intestinal epithelial barrier function have been implicated in the pathogenesis of ulcerative colitis (UC). Accordingly, restoration of epithelial barrier function as a means to reshape mucosal homeostasis represents an important strategy for use in the treatment of UC. In this study, we examined the role and mechanisms of D-mannose in the recovery of colitis as assessed in both animal and cell models. We found that D-mannose ameliorated inflammation, promoted mucosal healing in the colon and therefore was able to induce the recovery of UC. Furthermore, D-mannose increased the expression of tight junction (TJ) proteins and reduced the intestinal permeability during the recovery of colitis. Moreover, D-mannose inhibited M1 macrophage polarization and promoted M2 macrophage polarization via inducing AMPK phosphorylation while reducing mTOR phosphorylation in both models. In addition, increased TJ protein expression and decreased paracellular permeability were observed in NCM460 cells when incubated with the supernatants of D-mannose-treated RAW264.7 cells, suggesting that M1/M2 polarization induced by D-mannose modulates the expression of TJ proteins. Further study showed that D-mannose significantly upregulated the expression of TJ proteins in DSS-treated NCM460 cells by inducing AMPK phosphorylation, indicating a direct protective effect on epithelial cells. Finally, the protective effects of D-mannose were significantly abrogated by the presence of compound C, an AMPK inhibitor. Taken together, our data indicate that D-mannose can alleviate inflammation and foster epithelial restitution in UC recovery by inducing the TJ protein expression, which are achieved by inducing AMPK phosphorylation in the epithelium and/or macrophages.


Assuntos
Colite Ulcerativa , Colite , Animais , Camundongos , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Manose/metabolismo , Fosforilação , Mucosa Intestinal/metabolismo , Colite/induzido quimicamente , Colite Ulcerativa/induzido quimicamente , Inflamação/metabolismo , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , Sulfato de Dextrana/efeitos adversos , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Colo/metabolismo
6.
BMC Med Educ ; 23(1): 661, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37705019

RESUMO

BACKGROUND: Chinese universities are increasingly recruiting foreign students, and problem-based learning (PBL) is an effective approach to integrating those students. This study focuses on the role of intercultural sensitivity and group ethnic composition on the quality of group interaction in medical problem-based learning in China. METHODS: This paper reports an investigation of the differences in three types of group interaction (exploratory questions, cumulative reasoning, and handling conflict) among 139 s-year medical undergraduates from two backgrounds (Chinese and foreign) in a PBL setting. The roles of intercultural sensitivity, group ethnic composition, and students' personal characteristics including age, gender and ethnicity on students' perceptions of the three types of interaction were quantitatively analyzed. A 35-item questionnaire and demographic survey were administered to second year medical undergraduates. RESULTS: The results indicated that group ethnic composition was a significant negative predictor while intercultural sensitivity was a strong positive predictor of group interactions involving exploratory questions and cumulative reasoning. In addition, group heterogeneity in terms of age and ethnicity were significant predictors of group interaction. CONCLUSIONS: The findings of this study provide insights for strategically designing effective multiethnic group learning environments that encourage interaction and collaboration.


Assuntos
Dinâmica de Grupo , Aprendizagem Baseada em Problemas , Humanos , Povo Asiático , China , Etnicidade , Universidades
8.
Biomed Pharmacother ; 165: 115076, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37478578

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic disease with an unclear pathogenesis for which successful treatments are still lacking. It has been reported that procyanidin, a natural antioxidant, relieves colitis, but the specific mechanism is elusive. PURPOSE: Our present study was designed to investigate the effects of procyanidin on colitis and the regulation of the M1 macrophage phenotype and related signaling pathways. METHODS: In vivo, we used two classic colitis models to observe the effect of procyanidin on macrophage polarization. In vitro, we further validated the therapeutic effect of procyanidin in the RAW264.7 cell line and peritoneal macrophages. RESULTS: The current findings provide new evidence that procyanidin ameliorated dextran sulfate sodium (DSS)-induced colitis by preventing the polarization of macrophages to the M1 type and downregulating the levels of proinflammatory factors in cells. We also showed that procyanidin prevented lipopolysaccharide (LPS)-induced elevation of inflammatory cytokines and the activation of proinflammatory macrophages, which was achieved by activating the STAT3 and NF-κB pathways. CONCLUSIONS: This is the first study to demonstrate that procyanidin alleviates experimental colitis by inhibiting the polarization of proinflammatory macrophages. These data reveal new ideas for the pathogenesis and treatment of inflammatory diseases.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Proantocianidinas , Animais , Camundongos , Proantocianidinas/farmacologia , Proantocianidinas/uso terapêutico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Macrófagos/metabolismo , Doenças Inflamatórias Intestinais/tratamento farmacológico , Células RAW 264.7 , Citocinas/metabolismo , NF-kappa B/metabolismo , Sulfato de Dextrana/toxicidade , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
9.
J Cancer Res Clin Oncol ; 149(13): 11471-11489, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37391641

RESUMO

BACKGROUND: Cirrhosis is a serious condition characterized by the replacement of healthy liver tissue with scar tissue, which can progress to liver failure if left untreated. Hepatocellular carcinoma (HCC) is a concerning complication of cirrhosis. It can be challenge to identify individuals with cirrhosis who are at high risk of developing HCC, particularly in the absence of known risk factors. METHODS: In this study, statistical and bioinformatics methods were utilized to construct a protein-protein interaction network and identify disease-related hub genes. We analyzed two hub genes, CXCL8 and CCNB1, and developed a mathematical model to predict the likelihood of developing HCC in individuals with cirrhosis. We also investigated immune cell infiltration, functional analysis under ontology terms, pathway analysis, distinct clusters of cells, and protein-drug interactions. RESULTS: The results indicated that CXCL8 and CCNB1 were associated with the development of cirrhosis-induced HCC. A prognostic model based on these two genes was able to predict the occurrence and survival time of HCC. In addition, the candidate drugs were also discovered based on our model. CONCLUSION: The findings offer the potential for earlier detection of cirrhosis-induced HCC and provide a new instrument for clinical diagnosis, prognostication, and the development of immunological medications. This study also identified distinct clusters of cells in HCC patients using UMAP plot analysis and analyzed the expression of CXCL8 and CCNB1 within these cells, indicating potential therapeutic opportunities for targeted drug therapies to benefit HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/genética , Ciclina B1/metabolismo , Cirrose Hepática/genética , Cirrose Hepática/patologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/genética , Mapas de Interação de Proteínas/genética
10.
Front Genet ; 14: 1169190, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37229192

RESUMO

Stroke known as a neurological disease has significant rates of disability and mortality. Middle cerebral artery occlusion (MCAO) models in rodents is crucial in stroke research to mimic human stroke. Building the mRNA and non-conding RNA network is essential for preventing MCAO-induced ischemic stroke occurrence. Herein, genome-wide mRNA, miRNA, and lncRNA expression profiles among the MCAO group at 3 h, 6 h, and 12 h after surgery and controls using high-throughput RNA sequencing. We detected differentially expressed mRNAs (DE-mRNAs), miRNAs (DE-miRNAs), and lncRNAs (DE-lncRNAs) between the MCAO and control groups. In addition, biological functional analyses were conducted, including GO/KEGG enrichment analysis, and protein-protein interaction analysis (PPI). GO analysis indicated that the DE-mRNAs were mainly enriched in several important biological processes as lipopolysaccharide, inflammatory response, and response to biotic stimulus. The PPI network analysis revealed that the 12 DE-mRNA target proteins showed more than 30° with other proteins, and the top three proteins with the highest node degree were Alb, IL-6, and TNF. In the DE-mRNAs, we found the mRNA of Gp6 and Elane interacting with two miRNAs (novel_miR_879 and novel_miR_528) and two lncRNAs (MSTRG.348134.3 and MSTRG.258402.19). As a result of this study, a new perspective can be gained into the molecular pathophysiology leading to the formation of MCAO. The mRNA-miRNA‒lncRNA regulatory networks play an important role in MCAO-induced ischemic stroke pathogenesis and could be applied to the treatment and prevention of ischemic stroke in the future.

11.
Front Pharmacol ; 14: 1126235, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36814495

RESUMO

Anlotinib is an oral multi-targeted tyrosine kinase inhibitor as a third-line and subsequent treatment for patients with small cell lung cancer (SCLC) in China. The neurotoxicity is less reported. Posterior reversible encephalopathy syndrome (PRES) is characterized by headaches, seizures, encephalopathy, and visual disturbances, as well as focal reversible vasogenic edema seen on neuroimages. Here, we presented a case of PRES in a small cell lung cancer (SCLC) patient associated with anlotinib. A 37-year-old female patient, who had a history of diabetes, with extensive-stage SCLC received anlotinib after third-line chemotherapy. Ten cycles of anlotinib later, the patient experienced visual disturbance and was diagnosed with PRES based on the typical demyelination of white matter obtained in the brain magnetic resonance. During anlotinib therapy, the patient did not develop anti-VEGF therapy-induced hypertension. Subsequently, the patient stopped anlotinib, but she did not recover from symptoms. We also summarized the characteristics of fifty-four cases of PRES caused by antiangiogenic drugs in the literature. Based on our experience and the literature review, the incidence of PRES induced by antiangiogenic drugs is low, and the symptom can resolve upon stopping the medications. However, some cases still have a poor prognosis and the underlying mechanism requires further investigation. In addition, early detection and treatment of PRES are essential for physicians.

13.
J Neurosci Methods ; 386: 109781, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36586440

RESUMO

BACKGROUND: The enteric neural precursor cells (ENPCs) are important for researching the pathogenesis of enteric nervous system (ENS)-related diseases, especially in adulthood. Because primary ENPCs are difficult to isolate and survive, easy to contaminate and low-yielding, a rapid and effective method to isolate and cultivate ENPCs from adult mice is necessary. NEW METHODS: The longitudinal muscle myenteric plexus (LMMP) was isolated from the adult mouse colon. The papain and collagenase Ⅱ were chosen to increase the yield of ENPCs. The growth and proliferation of ENPCs could be promoted by using polylysine precoated culture plates and reasonable cell seeding density. The ENPCs were identified by Nestin and the proliferative properties were verified by EDU. The transgenic Nestin-cre:tdTomato mice were used to observe the proliferation of ENPCs more intuitively in vitro. RESULTS: Our method to isolate the ENPCs from adult mouse colon was effective and high-yielding. The ENPCs were identified as Nestin positive. The Nestin-positive ENPCs could proliferate rapidly and had a tendency to differentiate into neurons and glial cells in vitro without any inducing factors. COMPARISON WITH EXISTING METHODS: Previous studies about the ENPCs focused on experiment in vivo or were limited to the embryonic mice, and had limitations of low yield and long experiment time. The ENPCs from adult mice were isolated quickly by our method, and had a high yield and purity. CONCLUSION: We described a rapid, efficient, step by step method for isolation and culture of ENPCs from the adult mouse colon, which was simple and obtained high yield of ENPCs.


Assuntos
Células-Tronco Neurais , Camundongos , Animais , Nestina , Neurônios/fisiologia , Neuroglia , Colo
14.
Clin Sci (Lond) ; 137(1): 109-127, 2023 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-36503938

RESUMO

Menopausal women often face long-term estrogen treatment. G protein-coupled estrogen receptor (GPER) expressed in intestinal crypt was activated by estrogen therapy, but it was unclear whether chronic GPER activation during menopause had an effect on intestinal stem cells (ISCs). We tested the effect of chronic GPER activation on ISCs of ovariectomized (OVX) mice by injection of the selective GPER agonist G-1 for 28 days, or G-1 stimulation of organoids derived from crypts of OVX mice. G-1 up-regulated crypt depth, the number of Ki67+, bromodeoxyuridine+ cells and Olfm4+ ISCs, and the expression of ISCs marker genes (Lgr5, Olfm4 and Axin2). G-1 administration promoted organoid growth, increased the number of EdU+ cells per organoid and protein expression of Cyclin D1 and cyclin B1 in organoids. After G-1 treatment in vivo or in vitro, Paneth cell-derived Wnt3, Wnt3 effector ß-catenin and Wnt target genes c-Myc and Cyclin D1 increased in ileum or organoids. Once blocking the secretion of Wnt3 from Paneth cells, the effects of G-1 on organoids growth, ISCs marker genes and Wnt/ß-catenin signaling were abolished. G-1 did not affect the number of Paneth cells in ex vivo organoids, while activated Mmp7/cryptdin program in Paneth cells, promoted their maturation, and increased the expression of lysozyme protein. G-1 pretreatment in OVX mice inhibited radiation-induced ISCs proliferation injury and enhanced the resistance of mice to intestinal injury. In conclusion, chronic GPER activation prompted the Wnt3 synthesis in Paneth cells, thus increased the proliferation of ISCs via activation of Wnt3/ß-catenin signaling in OVX mice.


Assuntos
Ciclina D1 , Celulas de Paneth , Camundongos , Feminino , Animais , Celulas de Paneth/metabolismo , Ciclina D1/metabolismo , beta Catenina/metabolismo , Íleo/metabolismo , Células-Tronco , Via de Sinalização Wnt , Proliferação de Células , Estrogênios/farmacologia , Estrogênios/metabolismo , Mucosa Intestinal/metabolismo , Proteína Wnt3/metabolismo , Proteína Wnt3/farmacologia
15.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(11): 1219-1225, 2022 Nov 15.
Artigo em Chinês | MEDLINE | ID: mdl-36398547

RESUMO

OBJECTIVES: To develop the birth weight curves of the Chinese Han (26-41 weeks of gestation) and Zhuang (28-41 weeks of gestation) singleton neonates in 11 cities of China, as well as the birth weight means of full-term neonates of 14 Chinese ethnic groups. METHODS: The live singleton neonates who were born in 11 maternal and child health care hospitals from 11 cities of China between January 2017 and December 2020 were classified according to the mother's ethnic group. Birth weight means were calculated for the full-term neonates of each ethnic group. For the Han and Zhuang singleton neonates with a large sample size, the Lambda-Mu-Sigma (LMS) method was used to establish the birth weight percentile curves of the Han and Zhuang singleton neonates with different gestational ages. RESULTS: A total of 105 365 live singleton neonates were included, among whom the Han neonates had the highest number of 84 851 (26-41 weeks of gestation), followed by the Zhuang neonates (12 803 neonates with a gestational age of 28-41 weeks). The neonates of the other Chinese ethnic groups enrolled were live full-term singleton neonates, with a sample size of more than 100 neonates for each ethnic group. The 3rd-97th percentile curves of birth weight were established for the Han singleton neonates with a gestational age of 26-41 weeks and the Zhuang singleton neonates with a gestational age of 28-41 weeks. The birth weight curves of the Han singleton neonates at each gestational age were higher than those of the Zhuang singleton neonates. Birth weight means (3 199-3 499 g) and standard deviations were determined for 14 Chinese ethnic groups, i.e., Li, Mulao, Zhuang, Yao, Dong, Miao, Han, Buyi, Mongolian, Tujia, Yi, Hui, Man, and Korean ethnic groups. The Li ethnic group had the lowest birth weight, followed by the Mulao, Zhuang, Yao, Dong, Miao, Han, Buyi, Mongolian, Tujia, Yi, Hui, Man, and Korean ethnic groups. CONCLUSIONS: The 3rd-97th percentile curves of birth weight are developed for the Han (26-41 weeks of gestation) and Zhuang (28-41 weeks of gestation) singleton neonates in 11 cities of China, and birth weight means are determined for the full-term neonates of 14 Chinese ethnic groups in 11 cities of China, which provides a reference for evaluating the intrauterine growth of neonates in these ethnic groups.


Assuntos
Etnicidade , Recém-Nascido , Masculino , Criança , Humanos , Lactente , Peso ao Nascer , Cidades , Idade Gestacional , China
17.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(8): 899-907, 2022 Aug 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-36036129

RESUMO

OBJECTIVES: To develop the birth weight curve of twin neonates with a gestational age of 25-40 weeks, and to investigate the regional differences of the birth weight curve. METHODS: A total of 11 maternal and child health care hospitals with more than 7 000 neonates delivered annually were selected in 11 cities of China (Haikou, Guangzhou, Liuzhou, Guilin, Quanzhou, Shenzhen, Chongqing, Chengdu, Changsha, Ningbo, and Lianyungang), and all live twin neonates delivered in the 11 hospitals from January 1, 2017 to December 31, 2020 were enrolled for the development of birth weight curves. RESULTS: A total of 17 256 twin neonates with a gestational age of 25-40 weeks from the 11 cities were included in the study. The reference values of the 3rd-97th percentiles of birth weight of twin neonates for the total of the 11 cities and for each of the 11 cities in China were established, and the birth weight percentile curves were drawn. The birth weight curve level of twin neonates in Liuzhou was lower than the average level of the 11 cities; the birth weight curve level of twin neonates in Ningbo was higher than the average level of the 11 cities; the birth weight curve level of twin neonates in Lianyungang was obviously higher than the average level of the 11 cities; the birth weight curve level of twin neonates in other 8 cities was almost the same as the average level of the 11 cities. CONCLUSIONS: The reference values of the 3rd-97th percentiles of birth weight of twin neonates for the total of the 11 cities and for each of the 11 cities are developed, which can be used as a reference for evaluating the intrauterine growth of twin neonates in the region. The level of intrauterine growth of twin neonates in some cities is different from the average level of the 11 cities of China.


Assuntos
Gêmeos , Peso ao Nascer , Criança , China , Cidades , Idade Gestacional , Humanos , Lactente , Recém-Nascido
18.
BMC Med Educ ; 22(1): 560, 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35854299

RESUMO

BACKGROUND: Students can take different approaches to using online learning technologies: deep and surface. It is important to understand the relationship between instructor role and student approaches to using online learning technologies in online learning settings supported by cloud computing techniques. METHODS: A descriptive, cross-sectional study was conducted to analyze the relationships between medical students' perceptions of instructor role (instructor support, instructor-student interaction, and instructor innovation) and students' approaches to using online learning technologies in cloud-based virtual classrooms. A 25-item online questionnaire along with a sheet with basic demographic was administered to all medical students at Qilu Medical Schools of Shandong University China. Overall, 213 of 4000 medical students (5.34%) at the medical school participated in the survey. RESULTS: The results showed high levels of medical students' perceived instructor support, instructor-student interaction and instructor innovation. Most students adopted the deep approaches to using online learning technologies. Instructor support, instructor-student interaction and innovation were positively related to students' deep approaches to using online learning technologies. Instructor support was negatively related to students' surface approaches to using online learning technologies. CONCLUSIONS: The relationship between instructor role (instructor support, instructor-student interaction and instructor innovation) and students' approaches to using online learning technologies highlight the importance of instructor support and innovation in facilitating students' adoption of desirable approaches to learning from the application of technologies.


Assuntos
Educação a Distância , Estudantes de Medicina , Computação em Nuvem , Estudos Transversais , Educação a Distância/métodos , Humanos , Universidades
19.
Neurosci Lett ; 786: 136788, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-35835396

RESUMO

The association between dopamine D3 receptor (DRD3) Ser9Gly polymorphism and treatment response to antipsychotic drugs (APDs) in schizophrenia (SCZ) has been widely reported with inconsistent results, thus we performed an updated meta-analysis to derive a more precise estimation of the relationship. PubMed, Cochrane Library, Medline, Embase, CNKI, Weipu and Wanfang databases were searched for eligible studies published until March 2022. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of the associations in four genetic models. A total of 13 studies with 1769 patients were included in this meta-analysis. Our findings suggested that Ser9Gly polymorphism was significantly associated with treatment response to APDs in SCZ in allele model (Ser vs Gly, OR = 0.72, 95 % CI = 0.58-0.89, P = 0.002), recessive model (Ser/Ser vs Ser/Gly + Gly/Gly, OR = 0.55, 95 % CI = 0.36-0.86, P = 0.008) and co-dominant model (Ser/Ser vs Gly/Gly, OR = 0.57, 95 % CI = 0.33-0.99, P = 0.045) in Caucasians, but not in Asians. meta-regression revealed that the associations were not confounded by mean age, male ratio and treatment duration (P > 0.05). In summary, our results indicated the DRD3 Ser9Gly may influence the efficacy of APDs in specific genetic models, of which Ser allele and Ser/Ser genotype contributed to poor treatment response in Caucasians.


Assuntos
Antipsicóticos , Esquizofrenia , Antipsicóticos/uso terapêutico , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Polimorfismo Genético/genética , Polimorfismo de Nucleotídeo Único , Receptores de Dopamina D3/genética , Esquizofrenia/complicações , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética
20.
Front Pharmacol ; 13: 899169, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35754513

RESUMO

Ischemia/reperfusion injury is a common pathophysiological process in the clinic. It causes various injuries, multiple organ dysfunction, and even death. There are several possible mechanisms about ischemia/reperfusion injury, but the influence on intestinal myenteric neurons and the underlying mechanism are still unclear. C57BL6/J mice were used to establish the ischemia/reperfusion model in vivo. Peritoneal macrophages were used for ATP depletion and hypoxia/reoxygenation experiment in vitro. L-cysteine, as the substrate of hydrogen sulfide, is involved in many physiological and pathological processes, including inflammation, metabolism, neuroprotection, and vasodilation. In the current study, we confirmed that intestinal ischemia/reperfusion led to the injury of myenteric neurons. From experiments in vitro and in vivo, we demonstrated that L-cysteine protected myenteric neurons from the injury. AOAA reversed the protective effect of L-cysteine. Also, L-cysteine played a protective role mainly by acting on intestinal macrophages via decreasing the expression of NLRP3, cleaved caspase-1, and mature IL-1ß. L-cysteine increased cystathionine beta synthase and H2S produced by intestinal macrophages to protect myenteric mature neurons and enteric neural precursor cells from apoptosis. Moreover, the addition of IL-1ß-neutralizing antibody alleviated the injury of myenteric neurons and enteric neural precursor cells caused by intestinal ischemia/reperfusion. Our study provided a new target for the protection of myenteric neurons in clinical intestinal ischemia/reperfusion injury.

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