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1.
China Pharmacy ; (12): 186-191, 2024.
Artigo em Chinês | WPRIM | ID: wpr-1006176

RESUMO

OBJECTIVE To investigate the inhibitory effects of Ginkgo biloba extract (GBE) on renal inflammation in diabetic nephropathy (DN) model mice, and its potential mechanism. METHODS KK/Ay mice were fed with high fat and high sugar to induce DN model. They were divided into model group, positive control group [metformin 200 mg/(kg·d)], GBE low-dose and high-dose groups [100, 200 mg/(kg·d)], with 6 mice in each group. Six C57BL/6J mice were fed with a regular diet as the control group. Administration groups were given relevant liquid intragastrically, control group and model group were given constant volume of normal saline intragastrically, once a day, for 8 consecutive weeks. The body weight, fasting blood glucose, 24-hour food intake, 24-hour urine output, monocyte chemoattractant protein-1 (MCP-1), interleukin-12 (IL-12), IL-10, advanced glycation end products (AGEs), blood urea nitrogen (BUN) and serum creatinine (Scr) of mice were measured, and the ratio of bilateral kidneys to body weight was also calculated. The pathological injury and fibrotic changes of the renal cortex were observed, and the expressions of macrophage polarization marker proteins [type M1: inducible nitric oxide synthase (iNOS); type M2: arginase-1 (Arg-1)] and AGEs-the receptor of advanced glycation end products (RAGE)/Ras homolog gene pharm_chenjing@163.com family member A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) signaling pathway-related proteins were determined in renal cortex. RESULTS Compared with the model group, the symptoms such as renal cortical hyperplasia, vacuoles, infiltration of inflammatory cells, and renal cortical fibrosis had been improved in GBE low-dose and high-dose groups; body weight, serum level of IL-10, the expression of Arg-1 in the renal cortex were significantly higher than model group (P< 0.01); fasting blood glucose, 24-hour food intake, 24-hour urine output, serum levels of MCP-1, IL-12, BUN, Scr and AGEs, the ratio of bilateral kidneys to body weight, renal injury score, the proportion of renal interstitial fibrosis, the protein expressions of iNOS, RAGE, RhoA and ROCK1 (except for GBE low-dose group) in renal cortex were significantly lower than model group (P<0.01). CONCLUSIONS GBE could improve kidney damage and alleviate inflammatory response in DN model mice, the mechanism of which may be related to inhibiting the AGEs-RAGE/RhoA/ROCK signaling pathway and regulating macrophage polarization.

2.
Chinese Pharmacological Bulletin ; (12): 447-454, 2024.
Artigo em Chinês | WPRIM | ID: wpr-1013636

RESUMO

Aim Excessive cerebral inflammation caused by chronic alcohol intake is an important risk factor for central nervous system injury. The purpose of this study was to explore the protective effect of konjac mannan oligosaccharide (KMOS) on central nervous system inflammation in alcohol-fed mice and its mechanism. Methods The chronic alcohol fed model of C57BL/6J mice was established using Gao-binge method. And the different doses of KMOS were gavaged every day for 6 weeks. The neuronal damage and microglia activation were evaluated in cerebral cortex and hippocampus. The damage of colon tissue was assessed and serum LPS concentrations were measured. In vitro, Caco-2 cells were stimulated with LPS to establish intestinal mucosal injury model. Results Chronic alcohol intake can cause brain neuron damage in mice, and different doses of KMOS effectively reduced the activation state of microglia, decreased the expression of inflammatory factors caused by the activation of the NLRP3 inflammasome and alleviated neuronal damage in the brain tissue of alcohol-fed mice. The results of colon tissue analysis showed that the use of KMOS effectively reduced the concentration of endotoxin LPS in serum of alcohol-fed mice, alleviated the pathological injury and inflammatory response of colon tissue, and enhanced the expression of Occludin in intestinal tissue. In vitro experiments also showed that KMOS significantly inhibited the inflammatory reaction of Caco-2 cells exposed to alcohol and increased the expression of Occludin protein. Conclusions KMOS treatment effectively inhibited intestinal inflammation caused by alcohol intake, repaired intestinal barrier to prevent the entry of intestinal LPS into brain tissue, decreased the activation of microglia, and then improved brain neuron damage. KMOS had the potential to prevent alcoholic nerve injury.

3.
China Pharmacy ; (12): 689-694, 2024.
Artigo em Chinês | WPRIM | ID: wpr-1013103

RESUMO

OBJECTIVE To explore the neuroprotective effect of sodium aescinate on rats with Parkinson’s disease by regulating the silent information regulator 1 (SIRT1)/nuclear factor-κB (NF-κB) signaling pathway. METHODS The Parkinson’s disease rat model was constructed by using 6-hydroxydopamine injection method. Forty-eight rats successfully modeled were randomly divided into model group, sodium aescinate low-dose group (1.8 mg/kg), sodium aescinate high-dose group (3.6 mg/kg), sodium aescinate+EX527 (sodium aescinate 3.6 mg/kg+SIRT1 inhibitor EX527 5 mg/kg) group, with 12 rats in each group. Another 12 healthy rats were selected as the sham operation group. Each group was injected with the corresponding drug solution intraperitoneally, once a day, for 21 consecutive days. Twenty-four hours after the end of the last administration, the motor and cognitive functions of rats were detected, and the morphology of neurons in the substantia nigra and CA1 region of hippocampal tissue were observed. The content of dopamine (DA) in the nigrostriatal and the expression levels of tyrosine hydroxylase (TH) and α-synuclein (α-Syn) in the substantia nigra were detected. The serum levels of pro-inflammatory factor [interleukin-6 (IL-6), IL-18], anti-inflammatory factor (IL-10), and the expression levels of SIRT1, phosphorylated NF-κB p65 (p-NF-κB p65) and NF- κB p65 protein in nigrostriatal were detected. RESULTS Compared with sham operation group, the neurons in the substantia nigra and CA1 region of hippocampal tissue were seriously damaged in model group; the number of rotations, escape latency, the expression levels of α-Syn in substantia nigra, the levels of serum pro-inflammatory factors, the relative expression ratio of p-NF- κB p65 and NF-κB p65 protein in nigrostriatal were increased or prolonged significantly (P<0.05); the target quadrant residence time, the content of DA in nigrostriatal, the expression level of TH in substantia nigra, the serum level of anti-inflammatory factor, and the expression level of SIRT1 protein in substantia nigra striatum were significantly decreased or shortened (P<0.05). Compared with model group, the damage degrees of neuron in sodium aescinate groups were alleviated, and the quantitative indicators were significantly improved, which were more significant in the high-dose group (P<0.05); EX527 could reverse the improvement effect of high-dose sodium aescinate (P<0.05). CONCLUSIONS Sodium aescinate can inhibit the activation of NF-κB signal by up-regulating the protein expression of SIRT1, thereby reducing the neuroinflammation of rats with Parkinson’s disease, improving the motor and cognitive dysfunctions, and finally playing a neuroprotective role.

4.
Journal of Forensic Medicine ; (6): 447-451, 2023.
Artigo em Inglês | WPRIM | ID: wpr-1009376

RESUMO

OBJECTIVES@#To establish the menstrual blood identification model based on Naïve Bayes and multivariate logistic regression methods by using specific mRNA markers in menstrual blood detection technology combined with statistical methods, and to quantitatively distinguish menstrual blood from other body fluids.@*METHODS@#Body fluids including 86 menstrual blood, 48 peripheral blood, 48 vaginal secretions, 24 semen and 24 saliva samples were collected. RNA of the samples was extracted and cDNA was obtained by reverse transcription. Five menstrual blood-specific markers including members of the matrix metalloproteinase (MMP) family MMP3, MMP7, MMP11, progestogens associated endometrial protein (PAEP) and stanniocalcin-1 (STC1) were amplified and analyzed by electrophoresis. The results were analyzed by Naïve Bayes and multivariate logistic regression.@*RESULTS@#The accuracy of the classification model constructed was 88.37% by Naïve Bayes and 91.86% by multivariate logistic regression. In non-menstrual blood samples, the distinguishing accuracy of peripheral blood, saliva and semen was generally higher than 90%, while the distinguishing accuracy of vaginal secretions was lower, which were 16.67% and 33.33%, respectively.@*CONCLUSIONS@#The mRNA detection technology combined with statistical methods can be used to establish a classification and discrimination model for menstrual blood, which can distignuish the menstrual blood and other body fluids, and quantitative description of analysis results, which has a certain application value in body fluid stain identification.


Assuntos
Feminino , Humanos , RNA Mensageiro/metabolismo , Teorema de Bayes , Modelos Logísticos , Menstruação , Líquidos Corporais , Saliva , Sêmen , Genética Forense/métodos
5.
Artigo em Chinês | WPRIM | ID: wpr-1009327

RESUMO

OBJECTIVE@#To explore the long-term efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) in patients with Mucopolysaccharidosis (MPS), which has rarely been reported in China.@*METHODS@#A 18-month-old boy and a 23-month-old girl undergoing alloHSCT for MPS VI and MPS IH Shanghai Children's Medical Center on March 30, 2006 and September 6, 2006 were selected as the study subjects. A busulfan-based myeloablative regimen was used as the conditioning regimen. Peripheral stem cells were respectively collected from a human leucocyte antigen (HLA) matched sibling carrier donor and a HLA 9/10 matched unrelated donor. Both patients were followed up for more than 15 years. The functions of internal organs before and after the transplantation were compared, and child 1 was also compared with his untreated brother and healthy brother.@*RESULTS@#Both children have achieved full donor chimerism after the transplantation, and their enzymatic activities have remained stable. The enzymatic activity of the child 1 was slightly lower than normal but similar to that of his carrier donor, whilst that of the child 2 was normal. Both children have attended schools with good academic performance. Compared with his untreated brother, the respiratory function and hearing of child 1 have significantly improved. However, his orthopedic and cardiac disorders have still remained and required medical intervention. For child 2, her obstructive pulmonary disease was resolved and cognitive development was well preserved after the HSCT. Her heart disease has become stabilized and even improved with time, though her corneal clouding and skeletal malformation still required surgery.@*CONCLUSION@#MPS patients can sustain long-term and stable enzymatic activities after successful alloHSCT. Compared with untreated patients, their health can be significantly improved, along with considerably prolonged survival, though the long-term efficacy of HSCT for different organs may vary to a certain extent.


Assuntos
Humanos , Criança , Masculino , Feminino , Lactente , Pré-Escolar , Doença Enxerto-Hospedeiro/etiologia , China , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Mucopolissacaridoses/etiologia , Bussulfano , Resultado do Tratamento
6.
Artigo em Inglês | WPRIM | ID: wpr-1008990

RESUMO

This data article presents data from the China Migrants Dynamic Survey (CMDS), a multi-wave, large-scale national cross-sectional survey of China's internal migrants from 2009 to 2018. The CMDS is an annual questionnaire survey conducted by the former National Health and Family Planning Commission (NHFPC) of the People's Republic of China. The respondents included in this survey are internal migrants over 15 years old. The sample was drawn from the China Migrant Population Information System, using multi-stage stratified sampling method and the probability proportional-to-size (PPS) cluster sampling strategy. Between 2009 and 2018, there were 1,527,650 internal migrants from 23 provinces, 5 autonomous regions and 4 municipalities participated in the surveys. The survey tools were a series of self-designed questionnaires with high inheritance and consistency designed and implemented by the NHFPC. The questionnaires mainly contain basic information of the respondents and their family members, migration status, healthcare or health behaviors, public health service utilization, social insurance, social integration, and family planning. The dataset is currently the most widely used survey data on China's internal migrants, offering information on migration patterns, healthcare and health behaviors, use of public health services, access to social security, social integration, and family planning, which are valuable for health planning, health decision-making, and health equity research.


Assuntos
Humanos , Adolescente , Estados Unidos , Serviços de Planejamento Familiar , Migrantes , Estudos Transversais , China/epidemiologia , Inquéritos e Questionários
7.
Artigo em Chinês | WPRIM | ID: wpr-1008867

RESUMO

This study investigated the effect of eleutheroside B on apoptosis and autophagy of lung cancer A549 and H460 cells and its molecular mechanism. MTT assay was used to detect the cytotoxicity of eleutheroside B at 5, 10, 15, 20, 25, 30, 35, 40, and 45 mmol·L~(-1) on lung cancer cells. Trypan blue exclusion assay was used to detect the effect of eleutheroside B on the survival rate of lung cancer A549 and H460 cells at different time. Colony formation assay was used to detect the effect of eleutheroside B on the proliferation of lung cancer A549 and H460 cells. AO/EB fluorescence double staining and Hoechst 33342 fluorescence staining were used to detect the effect of eleutheroside B on apoptosis of lung cancer A549 and H460 cells, and Western blot was used to detect apoptosis-related proteins to explore the apoptosis-related molecular mechanism. AO fluorescence staining and Western blot were used to detect the expression of autophagic vesicles and autophagy-related proteins P62 and LC3. The results showed that compared with the control group, eleutheroside B inhibited the growth of lung cancer A549 and H460 cells in a concentration-dependent manner. The optimal effect time of eleutheroside B on lung cancer A549 and H460 cells was 24 h, and the optimal concentrations were 28.64 and 22.16 mmol·L~(-1), respectively. Eleutheroside B could inhibit the colony formation of A549 and H460 cells. Compared with the control group, eleutheroside B could promote the formation of apoptotic bodies and induce cell apoptosis, as well as induce the expression of mitochondrial pathway-related proteins. Under the effect of eleutheroside B, the acidic autophagy vacuole in lung cancer cells increased, LC3Ⅱ expression increased, P62 protein expression decreased, and PI3K, p-Akt, and p-mTOR protein expression decreased in the PI3K/Akt/mTOR pathway. Studies have shown that eleutheroside B can inhibit the growth of lung cancer cells, reduce colony formation, induce apoptosis of lung cancer cells through mitochondrial pathway, and induce autophagy. The mechanism may be related to the PI3K/Akt/mTOR pathway.


Assuntos
Humanos , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Apoptose , Proteínas Reguladoras de Apoptose , Autofagia , Proliferação de Células , Linhagem Celular Tumoral , Glucosídeos , Fenilpropionatos
8.
Acta Pharmaceutica Sinica B ; (6): 2736-2746, 2023.
Artigo em Inglês | WPRIM | ID: wpr-982867

RESUMO

The current targeting drug delivery mainly relies on cancer cell surface receptors. However, in many cases, binding affinities between protein receptors and homing ligands is relatively low and the expression level between cancer and normal cells is not significant. Distinct from conventional targeting strategies, we have developed a general cancer targeting platform by building artificial receptor on cancer cell surface via a chemical remodeling of cell surface glycans. A new tetrazine (Tz) functionalized chemical receptor has been designed and efficiently installed on cancer cell surface as "overexpressed" biomarker through a metabolic glycan engineering. Different from the reported bioconjugation for drug targeting, the tetrazine labeled cancer cells not only locally activate TCO-caged prodrugs but also release active drugs via the unique bioorthogonal Tz-TCO click-release reaction. The studies have demonstrated that the new drug targeting strategy enables local activation of prodrug, which ultimately leads to effective and safe cancer therapy.

9.
Artigo em Inglês | WPRIM | ID: wpr-982384

RESUMO

CUDC-101, an effective and multi-target inhibitor of epidermal growth factor receptor (EGFR), histone deacetylase (HDAC), and human epidermal growth factor receptor 2 (HER2), has been reported to inhibit many kinds of cancers, such as acute promyelocytic leukemia and non-Hodgkin's lymphoma. However, no studies have yet investigated whether CUDC-101 is effective against myeloma. Herein, we proved that CUDC-101 effectively inhibits the proliferation of multiple myeloma (MM) cell lines and induces cell apoptosis in a time- and dose-dependent manner. Moreover, CUDC-101 markedly blocked the signaling pathway of EGFR/phosphoinositide-3-kinase (PI3K) and HDAC, and regulated the cell cycle G2/M arrest. Moreover, we revealed through in vivo experiment that CUDC-101 is a potent anti-myeloma drug. Bortezomib is one of the important drugs in MM treatment, and we investigated whether CUDC-101 has a synergistic or additive effect with bortezomib. The results showed that this drug combination had a synergistic anti-myeloma effect by inducing G2/M phase blockade. Collectively, our findings revealed that CUDC-101 could act on its own or in conjunction with bortezomib, which provides insights into exploring new strategies for MM treatment.


Assuntos
Humanos , Antineoplásicos/uso terapêutico , Apoptose , Bortezomib/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Receptores ErbB/antagonistas & inibidores , Pontos de Checagem da Fase G2 do Ciclo Celular , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Células M , Mieloma Múltiplo/tratamento farmacológico
10.
Artigo em Chinês | WPRIM | ID: wpr-986988

RESUMO

OBJECTIVE@#To predict the targets and pathways in the therapeutic mechanism of Guizhi Gancao Decoction (GZGCD) against heart failure (HF) based on network pharmacology.@*METHODS@#The chemical components of GZGCD were analyzed using the databases including TCMSP, TCMID and TCM@Taiwan, and the potential targets of GZGCD were predicted using the SwissTargetPrediction database. The targets of HF were obtained using the databases including DisGeNET, Drugbank and TTD. The intersection targets of GZGCD and HF were identified using VENNY. Uniport database was used to convert the information, and the components-targets-disease network was constructed using Cytoscape software. The Bisogene plug-in, Merge plug-in, and CytoNCA plug-in in Cytoscape software were used for protein-protein interaction (PPI) analysis to acquire the core targets. Metascape database was used for GO and KEGG analysis. The results of network pharmacology analysis were verified with Western blot analysis. Three factors (PKCα, ERK1/2 and BCL2) were screened according to the degree value of network pharmacology results and the degree of correlation with heart failure process. The pentobarbtal sodium was dissolvein H9C2 cells treated with serum-free high glucose medium to simulate the ischemic anoxic environment of heart failure. The total proteins of myocardial cells were extracted. The protein contents of PKCα, ERK1/2 and BCL2 were determined.@*RESULTS@#We identified a total of 190 intersection targets between GZGCD and HF using Venny database, involving mainly the circulatory system process, cellular response to nitrogen compounds, cation homeostasis, and regulation of the MAPK cascade. These potential targets were also involved in 38 pathways, including the regulatory pathways in cancer, calcium signal pathway, cGMP-PKG signal pathway, and cAMP signal pathway. Western blot analysis showed that in an in vitro H9C2 cell model of HF, treatment with GZGCD downregulated PKCα and ERK1/2 expressions and upregulated BCL2 expression.@*CONCLUSION@#The therapeutic mechanism of GZGCD for HF involves multiple targets including PRKCA, PRKCB, MAPK1, MAPK3, and MAPK8 and multiple pathways including the regulatory pathway in cancer and the calcium signaling pathway.


Assuntos
Humanos , Proteína Quinase C-alfa , Farmacologia em Rede , Insuficiência Cardíaca/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2
11.
Artigo em Chinês | WPRIM | ID: wpr-986873

RESUMO

OBJECTIVE@#To explore the association between rs2587552 polymorphism (has a strong lin-kage disequilibrium with rs1800497 which had been found in many studies to be related to obesity, r2=0.85) of DRD2 gene and the effect of a childhood obesity intervention in Chinese population, and provide a scientific basis for future personalized childhood obesity intervention based on genetic background.@*METHODS@#From a multi-center cluster randomized controlled trial studying the effect of a childhood obesity intervention, we enrolled 382 children from 8 primary schools (192 and 190 children from intervention and control groups, respectively) in Beijing as study subjects. Saliva was collected and DNA was extracted to detect the rs2587552 polymorphism of DRD2 gene, and the interactions between the gene and study arms on childhood obesity indicators [including body weight, body mass index (BMI), BMI Z-score, waist circumference, hip circumference, waist-to-hip ratio, waist-to-height ratio, and body fat percentage] were analyzed.@*RESULTS@#No association was found between rs2587552 polymorphism and the changes in hip circumference or body fat percentage in the intervention group (P>0.05). However, in the control group, children carrying the A allele at DRD2 rs2587552 locus showed a greater increase in hip circumference and body fat percentage compared with those not carrying A allele (P < 0.001). There were interactions between rs2587552 polymorphism of DRD2 gene and study arms on the changes in hip circumference and body fat percentage (P=0.007 and 0.015, respectively). Compared with the control group, children in the intervention group carrying the A allele at DRD2 rs2587552 locus showed decrease in hip circumference by (-1.30 cm, 95%CI: -2.25 to -0.35, P=0.007) and decrease in body fat percentage by (-1.34%, 95%CI: -2.42 to -0.27, P=0.015) compared with those not carrying A allele. The results were consistent between the dominant model and the additive model (hip circumfe-rence: -0.66 cm, 95%CI: -1.28 to -0.03, P=0.041; body fat percentage: -0.69%, 95%CI: -1.40 to 0.02, P=0.056). No interaction was found between rs2587552 polymorphism and study arms on the changes in other childhood obesity-related indicators (P>0.05).@*CONCLUSION@#Children carrying the A allele at rs2587552 polymorphism of DRD2 gene are more sensitive to intervention and showed more improvement in hip circumference and body fat percentage after the intervention, suggesting that future personalized childhood obesity lifestyle intervention can be carried out based on the rs2587552 polymorphism of DRD2 gene.


Assuntos
Humanos , Criança , Obesidade Infantil/terapia , Estudos Prospectivos , Polimorfismo Genético , Índice de Massa Corporal , Circunferência da Cintura , Receptores de Dopamina D2/genética
12.
Chinese Journal of Pediatrics ; (12): 164-168, 2023.
Artigo em Chinês | WPRIM | ID: wpr-970257

RESUMO

Objective: To explore the short-term efficacy and safety of dapagliflozin in children with hereditary proteinuric kidney disease. Methods: This was a prospective cohort study. From August 2020 to December 2021, 23 children with hereditary kidney disease from Children's Hospital of Fudan University were enrolled. Patients received dapagliflozin 5 mg/d (weight≤30 kg) or initial dose 5 mg/d for 1 week, then 10 mg/d (weight>30 kg) and the dose of angiotensin converting enzyme inhibitors was stable during treatment. Clinical data including demographic parameters, primary diagnosis, estimated glomerular filtration rate (eGFR), 24 h proteinuria and characteristics in the follow-up were collected. The primary outcome was the change in 24 h proteinuria at 12 (±2) weeks, secondary outcomes included changes of 24 h proteinuria at 24 (±2) weeks, eGFR at both 12 (±2) and 24 (±2) weeks. The data were analysed by using mixed linear model. Results: Totally 23 patients were enrolled, including 16 males and 7 females. The age was (10.8±2.9) years. The primary diseases were Alport syndrome (12 cases), Dent disease (5 cases), proteinuria (4 cases), and focal segmental glomerulosclerosis (2 cases) respectively. Primary outcome showed that 24 h proteinuria decreased from baseline at 12 (±2) weeks during treatment (1.75 (1.46, 2.20) vs. 1.84 (1.14, 2.54) g/m2, P<0.05). Secondary outcomes showed that there was no significant difference in 24 h urine protein at 24 (±2) weeks (P>0.05). eGFR decreased slightly at 12 (±2) weeks ((107±21) vs. (112±28) ml/(min·1.73m2), P<0.05), and there was no significant difference at 24 (±2) weeks (P>0.05). Serum albumin increased at 12 (±2) and 24 (±2) weeks following the treatment ((39±8) vs. (37±8) g/L, (38±7) vs. (37±8) g/L, both P<0.05). No hypoglycemia event was reported during the treatment. Conclusion: The dapagliflozin had therapeutic effects on decreasing proteinuria and increasing serum albumin in short-term treatment in children with hereditary proteinuric kidney disease, no hypoglycemia or serious adverse events were observed.


Assuntos
Feminino , Masculino , Humanos , Criança , Adolescente , Estudos Prospectivos , Nefrite Hereditária , Proteinúria/tratamento farmacológico , Albumina Sérica
13.
Artigo em Chinês | WPRIM | ID: wpr-995310

RESUMO

Objective:To investigate whether KtrA was a binding protein of c-di-AMP, the second messenger in Leptospira, and to explore the function and regulatory mechanism of the c-di-AMP-KtrA/B system. Methods:KtrA gene was amplified by PCR and cloned into pET42a plasmid to construct the pET42a ktrA prokaryotic expression vector. Then the vector was transferred into E. coli BL21DE3 to construct an engineering bacterium E. coli BL21DE3 pET42a-ktrA for the expression of recombinant KtrA (rKtrA). The expressed rKtrA was purified by affinity chromatography. BIAcore technology was used to detect the binding ability of rKtrA to c-di-AMP. Bacterial two-hybrid analysis was used to analyze the interaction between KtrA and KtrB in the leptospiral Ktr system with or without exogenetic c-di-AMP. The above genes were then complemented into the potassium transport-deficient E. coli mutants to analyze the function of the c-di-AMP-KtrA/B pathway. Results:An prokaryotic engineering bacterium for the expression of ktrA gene of Leptospira was constructed successfully. The purified rKtrA could specifically bind to c-di-AMP. There was interaction between KtrA and KtrB, but the interaction could be dissociated by c-di-AMP. The KtrA/B system was involved in potassium ion uptake and it was negatively regulated by c-di-AMP. Conclusions:Leptospiral KtrA was a c-di-AMP-binding protein and the c-di-AMP-KtrA/B system was involved in potassium ion transport.

14.
Artigo em Chinês | WPRIM | ID: wpr-995216

RESUMO

Objective:To analyze the diagnostic value of preoperative electromyography and spasticity assessment for patients with hemifacial spasm, and to define a relationship between intraoperative electrophysiological examination and prognosis in order to provide help for clinical diagnosis and treatment.Methods:Thirty-one patients with hemifacial spasm were selected for the clinical spasticity scoring and divided into a general spasm group ( n=27) and a severe spasm group ( n=4). All received preoperative neurophysiological examination to record their twitch discharge, facial nerve conduction velocity (MCV), lateral spread (LSR) of the spasm, brainstem auditory evoked potential (BAEP), and blink reflex. Electrophysiological monitoring then recorded intraoperative LSR. According to whether the LSR disappeared or not, the patients were divided into the LSR disappearance group (of 15) and the LSR residual group (of 16), and facial muscle activity was recorded again one, three and six months after the operation. Results:Preoperative EMG examination of both groups showed positive LSR and that facial nerve MCV was within the normal range. There were, though, significant differences between the two groups in the twitching discharge by needle electromyography, blink reflex and preoperative BAEP. One week after the operation, one member of the residual group and 3 from the disappearance patients of the former and latter group had recovered in terms of LSR, with 3 and 7 cases significantly relieved, respectively. Two months later, the corresponding figures were 5 and 7, 3 and 6, respectively. Half of a year after the surgery, 5 from the residual group and 12 from the disappearance group had fully recovered in terms of LSR, while 9 and 2 cases were significantly relieved. Altogether, there were significant differences within the two groups in terms of recovery among all the time points, with significantly better recovery in the LSR disappearance group than the LSR residual group at 1 week after operation, while there were no significant differences between the two groups in recovery 3 and 6 months after their operation.Conclusions:Preoperative electromyography can provide objective assessments of the scope, severity, and facial nerve excitability of patients with hemifacial spasm. Real-time intraoperative electrophysiology monitoring can help surgeons to objectively assess the effect of decompression and to find and avoid nerve traction injury in surrounding areas quickly.

15.
Artigo em Chinês | WPRIM | ID: wpr-995208

RESUMO

Objective:To explore any effect of combining intermittent theta-burst stimulation (iTBS) of the cerebellum with physiotherapy on the balance function and gait of stroke survivors.Methods:Thirty-two hemiplegic stroke survivors were divided at random into a treatment group and a control group, each of 16. Both groups received conventional physical therapy. Before their physiotherapy sessions the treatment group received iTBS treatment of the cerebellar hemisphere contralateral to the affected cerebral hemisphere, while the control group was given pseudo-stimulation on the same site. The iTBS was given once a day for 200s each time, 6 times a week for 3 weeks consecutively. Before and after the treatment, as well as 3 weeks later, both groups′ balance was evaluated using the Berg Balance Scale (BBS). Their ability to shift their center of gravity, total length of their shaking trajectory, and maximum shaking diameter were also quantified. Walking ability was assessed using 10m walk test (10MWT) times and the Tinetti Gait Assessment Scale (POMA-G). Lower limb motor function was quantified using the relevant Fugl-Meyer assessment (FMA-LE) and the subjects′ ability in the activities of daily living was measured with the Barthel index (BI).Results:After the 3 weeks of treatment and at the follow-up the average BBS score of the treatment group had improved significantly more than the control group′s average, as had its total track length and maximum shake diameter. The average POMA-G, FMA-LE and BI scores of the treatment group were also significantly better.Conclusions:Combining iTBS with physiotherapy can improve the balance and gait of stroke survivors more effectively than physiotherapy alone.

16.
Chinese Journal of Nephrology ; (12): 620-623, 2023.
Artigo em Chinês | WPRIM | ID: wpr-995026

RESUMO

The paper summarizes the clinical and follow-up data of percutaneous endoscopic gastrostomy (PEG) in three infants with chronic kidney disease to explore the safety and reliability of using PEG to improve the growth and development, and nutritional status. During follow-up, the weight and height of case 1 and 3 were obviously improved. Case 2 was followed up for 3 months, due to dying of cardiac arrest, and the infant's height and weight were not significantly improved. Serum albumin and prealbumin improved in 3 cases after PEG. No PEG-related infection occurred in 3 infants.

17.
Chinese Journal of Nephrology ; (12): 85-94, 2023.
Artigo em Chinês | WPRIM | ID: wpr-994951

RESUMO

Objective:To evaluate the extent and progression of coronary artery calcification in maintenance hemodialysis (MHD) patients, and to explore the risk factors of rapid progression of coronary artery calcification in MHD patients.Methods:The patients who underwent MHD in the Huashan Hospital affiliated to Fudan University from January 1, 2013 to December 31, 2017 were enrolled. This study included cross-sectional study and prospective cohort study. Multi-slice spiral computed tomography was used to measure coronary artery calcification, and coronary artery calcium score (CACS) was calculated. In the cross-sectional study, 62 MHD patients were enrolled. According to baseline CACS, the patients were divided into low calcification group (CACS < 100) and high calcification group (CACS ≥ 100). The nutritional and bone mineral metabolism indexes were compared between the two groups. Multiple linear regression analysis was used to analyze the correlation between CACS and muscle mass and laboratory indicators. Since 6 patients were lost to follow-up, 56 MHD patients who were followed-up regularly were enrolled in the prospective cohort study. According to the progression of CACS, the patients were divided into slow progression group (ΔCACS/year < 100) and rapid progression group (ΔCACS/year ≥ 100). Logistic regression equation was used to analyze the risk factors of coronary calcification progression. Hosmer-Lemeshow goodness of fit test and receiver operating characteristic curve were used to evaluate the performance of multivariate logistic regression model.Results:In the cross-sectional study, the age of 62 patients was (62.34±10.82) years old, and the median dialysis age was 78 (39,139) months. Among the 33 male patients, compared with the low calcification group ( n=7), the high calcification group ( n=26) had older age ( t=-2.281, P=0.030) and higher blood triglyceride ( Z=-1.985, P=0.047), and there was no statistically significant difference in muscle mass between the two groups; among the 29 female patients, the muscle mass/height 2 ( t=-2.600, P=0.015) and serum calcium ( t=-2.641, P=0.014) in the high calcification group ( n=15) were both higher than those in the low calcification group ( n=14), and the hemoglobin level was lower ( t=2.531, P=0.018), and the difference in muscle mass between the two groups was not statistically significant. High sensitivity C-reactive protein ( β=0.425, P=0.022) was independently correlated with CACS in male patients, and muscle mass/extracellular water ( β=-0.580, P=0.001) was independently correlated with CACS in female patients. In the prospective cohort study, the age of 56 patients was (59.82±11.14) years old, and the median dialysis age was 82 (40, 146) months. There was no significant difference in all-cause mortality between slow progression group ( n=22) and rapid progression group ( n=34), but the proportion of cardiovascular events in rapid progression group was significantly higher than that in slow progression group ( P=0.017). Compared with the slow progression group, the rapid progression group had higher proportion of males ( χ2=4.791, P=0.029), older age ( Z=-2.131, P=0.038), lower baseline muscle mass/extracellular water ( Z=2.482, P=0.016) and high-density lipoprotein cholesterol ( t=2.133, P=0.042), and faster rate of muscle mass loss (Δmuscle mass·height -2·year -1) ( Z=-2.282, P=0.023). Multivariate logistic regression analysis results showed that muscle mass loss ( OR=0.089, 95% CI 0.010-0.792, P=0.030) and baseline CACS ( OR=1.003, 95% CI 1.000-1.005, P=0.021) were influencing factors for progression of coronary artery calcification in MHD patients. Conclusion:Increasing baseline CACS and rapid reduction in muscle mass are risk factors for the progression of coronary artery calcification in MHD patients.

18.
Chinese Journal of Neurology ; (12): 30-38, 2023.
Artigo em Chinês | WPRIM | ID: wpr-994796

RESUMO

Objective:To investigate the relationship between intracranial arterial remodeling and imaging markers in patients with cerebral small vessel disease (CSVD).Methods:One hundred and fifty-six patients with CSVD who were admitted to the Department of Neurology of the Second Affiliated Hospital of Zhengzhou University or the Public People′s Hospital of Xinzheng from January 2020 to May 2022 were selected, and their brain artery remodeling (BAR) score was calculated. The patients with BAR score≤-1 standard deviation (SD) were defined as individuals with constrictive remodeling of intracranial arteries, and the patients with BAR score≥1 SD were defined as individuals with dilated remodeling of intracranial arteries. Imaging markers of CSVD [white matter hyperintensities (WMHs), lacune, cerebral microbleeds, enlarged perivascular spaces, and cerebral atrophy] were quantified, total CSVD load was calculated and patients were divided into low load group (0-2 points, n=91) and high load group (3-4 points, n=65) according to the total CSVD load scores. The correlation between intracranial artery remodeling and various imaging markers of CSVD and total load was analyzed by using univariate analysis and binary Logistic regression analysis. A nomogram prediction model was established and a receiver operating characteristic curve (ROC) was drawn to assess the predictive value of intracranial artery remodeling on high total CSVD load. Results:Dilated intracranial arterial remodeling was an independent influence factor on severe WMHs ( OR=3.66, 95% CI 1.38-9.72, P=0.009), lacune ( OR=3.78, 95% CI 1.17-12.19, P=0.026), cerebral atrophy ( OR=3.11, 95% CI=1.10-8.81, P=0.033), and high total CSVD load ( OR=6.66, 95% CI=2.14-20.77, P=0.001). Age was an independent influencing factor for high total CSVD load ( OR=1.12, 95% CI 1.07-1.16, P<0.01). A nomogram prediction model for high total CSVD load with age and BAR score≥1 SD as dependent variables had a good effect (C-index=0.826) and calibration ( P=0.024). The best cut-off point of ROC curve was 0.50, with an area under the curve of 0.83 (95% CI 0.76-0.89, P<0.01), the sensitivity and specificity of 0.72 and 0.82. Conclusions:Patients with dilated intracranial arterial remodeling may have a heavier CSVD load. Dilated intracranial arterial remodeling may serve as a new biomarker for assessing CSVD, but the mechanism of the association needs further study.

19.
Artigo em Chinês | WPRIM | ID: wpr-994155

RESUMO

Objective:To investigate the current situation of clinical help-seeking of anesthesiologists and analyze the influencing factors of help-seeking behaviors in order to provide a basis for improving the help-seeking ability of anesthesiologists.Methods:The anesthesiologists in 35 public hospitals in Hubei province were investigated using a self-designed questionnaire, and the demographic differences and influencing factors related to help-seeking were analyzed.Results:The score for the help-seeking attitude questionnaire of anesthesiologists was (3.6±0.4). The score for the help-seeking needs sub-questionnaire of anesthesiologists was (2.7±0.6), and the score for the help-seeking behavior sub-questionnaire was (3.0±0.4). The item with the highest score was " special patients or patient emergency needs help", and the item with the lowest score was " self injury potential needs help". There was a statistically significant difference in the scores for the help-seeking needs sub-questionnaire for anesthesiologists of different ages and working years ( P<0.05), and there was no statistically significant difference in the scores for the help-seeking attitude questionnaire and help-seeking behavior sub-questionnaire for anesthesiologists of different genders, ages, professional titles, working years, personnel types, and whether they obtained a doctor′s license ( P>0.05). The percentage of anesthesiologists who believed that " they did not ask for help timely or without asking for help" was 35.4%, and the percentage of anesthesiologists who believed that " colleagues did not ask for help timely or without asking for help" was 50.7%. Among the reasons why the need for help did not translate into help-seeking behavior, the percentage of anesthesiologists who believed that " doctors think they can solve" was the highest (74.0%). Conclusions:Anesthesiologists in public hospitals have a positive attitude towards seeking-help and can better translate the need for help into behaviors. The main reasons for delay in seeking-help or non-seeking-help are inaccurate assessment of their own ability and inability to grasp the opportunity of seeking-help, and targeted training should be carried out to improve the doctors′ help-seeking ability.

20.
Artigo em Chinês | WPRIM | ID: wpr-993182

RESUMO

Objective:To improve the quality assurance (QA) skills of radiotherapy personnel and medical students and reduce the radiation risk of training by developing a remote training system for QA of medical electronic linear accelerators.Methods:This training system was built based on radiotherapy technology and quality control contents of medical electronic linear accelerators, and a virtual reality interactive software was developed using extended reality (XR) technology Unity 3D. A remote control module of multi-terminal platform was also developed. A multi-perspective evaluation system was adopted and a questionnaire was designed to analyze the application value of this system.Results:The training system reproduced the live environment and physical objects of medical electronic linear accelerator treatment room. It built a multi-terminal virtual simulation training system with radiotherapy technology as well as QA knowledge system. This system could provide 5G remote control of medical electronic linear accelerator for off-site quality control demonstration and guidance. By March 1, 2022, a total number of 133 people had been trained using this system, 76 valid questionnaires had been taken, of which 90.79% (69/76) of the respondents trusted the experimental results shown by the system and 88.16% (67/76) of the respondents considered the training system necessary.Conclusions:The training effect of this system is widely recognized. It fundamentally reduces the training radiation hazard and provides reference for the reform and progress of QA training mode of medical electronic linear accelerators.

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