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ObjectiveTo investigate the effect of NOD-like receptor family pyrin domain containing 3 (NLRP3) knockdown on a mouse model of nonalcoholic steatohepatitis (NASH) induced by high-fat high-carbohydrate (HFHC) diet. MethodsA total of 44 mice were randomly divided into normal diet group (CON group) with 20 mice and HFHC group with 24 mice. At the end of week 14 of modeling, 4 mice were randomly selected from the HFHC group for the pre-experiment of adeno-associated virus (AAV) by tail vein injection, and NLRP3 knockdown was verified after 4 weeks. After NLRP3 knockdown was verified at the end of week 18, the remaining 40 mice were given a single tail vein injection of AAV, and then they were divided into CON+NLRP3 knockdown negative control group (CON+NLRP3-NC group), CON+NLRP3 knockdown group (CON+NLRP3-KD group), HFHC+NLRP3-NC group, and HFHC+NLRP3-KD group, with 10 mice in each group. At the end of week 24, the activation of NLRP3 inflammasome was observed; related indicators were measured, including body weight, liver weight, liver index, and glucose metabolism (fasting blood glucose, fasting insulin, and Homeostasis Model Assessment of Insulin Resistance [HOMA-IR] index); the indicators of liver lipid content (liver triglyceride [TG] and oil red O staining), liver inflammation (serum alanine aminotransferase [ALT] activity, HE staining, and inflammation-related genes), and liver fibrosis (Sirius Red staining and fibrosis-related genes) were measured. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the CON+NLRP3-NC group based on the results of Western Blot, the HFHC+NLRP3-NC group had significant increases in the protein expression levels of NLRP3, pro-Caspase1, Caspase1, ASC, and IL-1β, while the HFHC+NLRP3-KD group had significant reductions in these levels (all P<0.05). The HFHC+NLRP3-NC group showed varying degrees of increase in body weight, liver weight, liver index, and glucose metabolism indicators, while the HFHC+NLRP3-KD group showed significant improvements in these indicators (all P<0.05). As for hepatic fat deposition, compared with the CON+NLRP3-NC group, the HFHC+NLRP3-NC group had a significant increase in liver TG, with a large number of red lipid droplets shown by oil red O staining, and the HFHC+NLRP3-KD group had significant reductions in liver TG and the number of lipid droplets in the liver (all P<0.01). In terms of liver inflammation, compared with the CON+NLRP3-NC group, the HFHC+NLRP3-NC group had significant increases in serum ALT, NAFLD activity score, and inflammation-related genes, while the HFHC+NLRP3-KD group had significant reductions in these indicators (all P<0.01). As for liver fibrosis, compared with the CON+NLRP3-NC group, the HFHC+NLRP3-NC group had significant increases in collagen fiber area and fibrosis-related genes, and the HFHC+NLRP3-KD group had significant reductions in fibrosis-related genes (all P<0.05) and a tendency of reduction in collagen fiber area (P>0.05). ConclusionNLRP3 knockdown can significantly improve hepatic fat deposition and inflammation in a mouse model of HFHC-induced NASH.
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Objective: To explore the prognostic value of circulating tumor DNA (ctDNA) testing in patients with refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL) undergoing chimeric antigen receptor T-cell (CAR-T) therapy, and to guide the prevention and subsequent treatment of CAR-T-cell therapy failure. Methods: In this study, 48 patients with R/R DLBCL who received CAR-T-cell therapy at the First Affiliated Hospital of Zhejiang University School of Medicine between December 2017 and March 2022 were included. Furthermore, ctDNA testing of 187 lymphoma-related gene sets was performed on peripheral blood samples obtained before treatment. The patients were divided into complete remission and noncomplete remission groups. The chi-square test and t-test were used to compare group differences, and the Log-rank test was used to compare the differences in survival. Results: Among the patients who did not achieve complete remission after CAR-T-cell therapy for R/R DLBCL, the top ten genes with the highest mutation frequencies were TP53 (41%), TTN (36%), BCR (27%), KMT2D (27%), IGLL5 (23%), KMT2C (23%), MYD88 (23%), BTG2 (18%), MUC16 (18%), and SGK1 (18%). Kaplan-Meier survival analysis revealed that patients with ctDNA mutation genes >10 had poorer overall survival (OS) rate (1-year OS rate: 0 vs 73.8%, P<0.001) and progression-free survival (PFS) rate (1-year PFS rate: 0 vs 51.8%, P=0.011) compared with patients with ctDNA mutation genes ≤10. Moreover, patients with MUC16 mutation positivity before treatment had better OS (2-year OS rate: 56.8% vs 26.7%, P=0.046), whereas patients with BTG2 mutation positivity had poorer OS (1-year OS rate: 0 vs 72.5%, P=0.005) . Conclusion: ctDNA detection can serve as a tool for evaluating the efficacy of CAR-T-cell therapy in patients with R/R DLBCL. The pretreatment gene mutation burden, mutations in MUC16 and BTG2 have potential prognostic value.
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Humanos , Prognóstico , Receptores de Antígenos Quiméricos , DNA Tumoral Circulante/genética , Estudos de Viabilidade , Linfoma Difuso de Grandes Células B/terapia , Linfoma não Hodgkin , Mutação , Terapia Baseada em Transplante de Células e Tecidos , Estudos Retrospectivos , Proteínas Imediatamente Precoces , Proteínas Supressoras de TumorRESUMO
Objective: To analyze the clinical features, efficacy and prognosis factors of core binding factor (CBF) acute myeloid leukemia (AML) children in South China. Methods: This was a retrospective cohort study. Clinical data of 584 AML patients from 9 hospitals between January 2015 to December 2020 was collected. According to fusion gene results, all patients were divided into two groups: CBF-AML group (189 cases) and non-CBF-AML group (395 cases). CBF-AML group were divided into AML1-ETO subgroup (154 cases) and CBFβ-MYH11 subgroup (35 cases). Patients in CBF-AML group chosen different induction scheme were divided into group A (fludarabine, cytarabine, granulocyte colony stimulating factor and idarubicin (FLAG-IDA) scheme, 134 cases) and group B (daunorubicin, cytarabine and etoposide (DAE) scheme, 55 cases). Age, gender, response rate, recurrence rate, mortality, molecular genetic characteristics and other clinical data were compared between groups. Kaplan-Meier method was used for survival analysis and survival curve was drawn. Cox regression model was used to analyze prognostic factors. Results: A total of 584 AML children were diagnosed, including 346 males and 238 females. And a total of 189 children with CBF-AML were included, including 117 males and 72 females. The age of diagnosis was 7.3 (4.5,10.0)years, and the white blood cell count at initial diagnosis was 21.4 (9.7, 47.7)×109/L.The complete remission rate of the first course (CR1) of induction therapy, relapse rate, and mortality of children with CBF-AML were significantly different from those in the non-CBF-AML group (91.0% (172/189) vs. 78.0% (308/395); 10.1% (19/189) vs. 18.7% (74/395); 13.2% (25/189) vs. 25.6% (101/395), all P<0.05). In children with CBF-AML, the CBFβ-MYH11 subgroup had higher initial white blood cells and lower proportion of extramedullary invasion than the AML1-ETO subgroup, with statistical significance (65.7% (23/35) vs. 14.9% (23/154), 2.9% (1/35) vs. 16.9% (26/154), both P<0.05). AML1-ETO subgroup had more additional chromosome abnormalities (75/154), especially sex chromosome loss (53/154). Compared with group B, group A had more additional chromosome abnormalities and a higher proportion of tumor reduction regimen, with statistical significance (50.0% (67/134) vs. 29.1% (16/55), 34.3% (46/134) vs. 18.2% (10/55), both P<0.05). Significant differences were found in 5-years event free survival (EFS) rate and 5-year overall survival (OS) rate between CBF-AML group and non-CBF-AML group ((77.0±6.4)%vs. (61.9±6.7)%,(83.7±9.0)%vs. (67.3±7.2)%, both P<0.05).EFS and OS rates of AML1-ETO subgroup and CBFβ-MYH11 subgroup in children with CBF-AML were not significantly different (both P>0.05). Multivariate analysis showed in the AML1-ETO subgroup, CR1 rate and high white blood cell count (≥50×109/L) were independent risk factors for EFS (HR=0.24, 95%CI 0.07-0.85,HR=1.01, 95%CI 1.00-1.02, both P<0.05) and OS (HR=0.24, 95%CI 0.06-0.87; HR=1.01, 95%CI 1.00-1.02; both P<0.05). Conclusions: In CBF-AML, AML1-ETO is more common which has a higher extramedullary involvement and additional chromosome abnormalities, especially sex chromosome loss. The prognosis of AML1-ETO was similar to that of CBFβ-MYH11. The selection of induction regimen group FLAG-IDA for high white blood cell count and additional chromosome abnormality can improve the prognosis.
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Masculino , Feminino , Humanos , Criança , Estudos Retrospectivos , Proteína 1 Parceira de Translocação de RUNX1/genética , Subunidade alfa 2 de Fator de Ligação ao Core/uso terapêutico , Prognóstico , Leucemia Mieloide Aguda/genética , Citarabina/uso terapêutico , Proteínas de Fusão Oncogênica/genética , Aberrações CromossômicasRESUMO
Objective: To investigate the impact of orthotopic liver transplantation on serum lipid and growing development in patients with homozygous (HoFH) or compound heterozygotes (cHeFH) familial hypercholesterolemia. Methods: Patients who were treated in Peking Union Medical College Hospital from August 2019 to August 2021, entered the rare disease database and underwent liver transplantation, were included in this single center retrospective cohort study. The height for age Z score (HAZ) and length for age Z score (WAZ) at birth, at the time of transplantation and one year after transplantation were calculated respectively by collecting demographic characteristics, clinical manifestations, echocardiography, lipid-lowering treatment, blood lipid level data and donor characteristics data of liver transplantation. The serum cholesterol level and growing development changes before and after liver transplantation were evaluated. Results: A total of five patients with HoFH or cHeFH, including two females, were included in this study. The median age was 10 years (6-22 years). The median follow up duration was 28 months (24-33 months). All HoFH or cHeFH patients in this study received the maximum daily dosage of the lipid-lowering drug combined with low salt and low-fat diet control treatment for at least 3 months before orthotopic liver transplantation. The average level of total cholesterol (TC) decreased by 27% compared with that before treatment, the level of low-density lipoprotein cholesterol (LDL-C) decreased by 21% after 3 months treatment. There was no intervention of lipid-lowering therapy after operation. One month after liver transplantation, the average levels of TC and LDL-C further decreased rapidly by 68% and 76% respectively. One year after liver transplantation, the level of LDL-C decreased from (17.1±1.6)mmol/L without any intervention before transplantation to (3.0±0.7)mmol/L, and remained stable thereafter. In addition, compared with no intervention before liver transplantation, the serum triglyceride (TG) level decreased after the maximum daily dosage of the lipid-lowering drug and low salt and low-fat diet control for 3 months ((1.88±0.27) mmol/L vs. (1.12±0.55)mmol/L, P=0.031), and the HDL-C level also decreased significantly ((1.95±0.49)mmol/L vs. (0.95±0.30)mmol/L, P=0.006) at the same time period. TG and HDL-C remained stable after liver transplantation during the 24-month follow-up period (P>0.05). One and two years after liver transplantation, there was no significant difference in height and weight, malnutrition and growth retardation between the patients in this cohort and Chinese children of the same age. Conclusion: Early liver transplantation is a feasible and effective treatment option for HoFH or cHeFH patients with extremely high serum low-density lipoprotein cholesterol levels.
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Criança , Recém-Nascido , Feminino , Humanos , LDL-Colesterol/uso terapêutico , Transplante de Fígado , Hipercolesterolemia Familiar Homozigota , Estudos Retrospectivos , Hiperlipoproteinemia Tipo II/cirurgia , Lipídeos , Hipolipemiantes/uso terapêuticoRESUMO
Three different preclinical evaluation methods of MTF through-frequency response, MTF through-focus-response and expected visual acuity were used to compare and analyze the imaging differences of IOLs with four different optical designs. The research work could be used in the simultaneous vision IOLs in the optical design stage and verify the optical quality of the IOLs, the results can predict the visual representation of the patients better. The evaluation results can provide reference for IOL manufacturers and users in product design, development, validation and application selection.
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Humanos , Desenho de Prótese , Lentes Intraoculares , Visão Ocular , Acuidade VisualRESUMO
Objective: To explore the application effects of feedforward control theory in the rollover bed treatment of mass patients with burn-explosion combined injury. Methods: A retrospective observational research was conducted. From June 13 to 14, 2020, 15 patients with severe burn-explosion combined injury caused by liquefied natural gas tank car explosion and conforming to the inclusion criteria were admitted to the Second Affiliated Hospital of Zhejiang University School of Medicine. There were 13 males and 2 females, aged 33-92 (66±17) years. All the patients were treated with rollover bed from 48 h post admission, and the feedforward control theory was introduced, including establishing a special feedforward control management team for rollover bed, clarifying the duties of the medical staff in the rollover bed treatment of patients, implementing the cooperation strategy of multidisciplinary physician, training and examining for 80 nurses in the temporarily organized nurse team in the form of "rollover bed workshop", and formulating the checklist and valuation list of rollover bed treatment for continuous quality control. The frequency and the total number of turning over, and successful rate of one-time posture change with the rollover bed of patients within 30 days of admission were recorded, the occurrences of adverse events caused by improper operation for the rollover bed during the treatment were observed, including respiratory and cardiac arrests, treatment interruption, unplanned extubation, bed falling, and skin graft displacement. The lowest levels of arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2), the number of patients with oxygenation index>300 mmHg (1 mmHg=0.133 kPa), and the occurrence of acute respiratory distress syndrome (ARDS) of patients within 2 days of admission and on the 30th day of admission were recorded. Results: Within 30 days of admission, the patients were turned over with the rollover bed for 2 to 6 times each day, with a total of 1 320 turning over operations, the successful rate of one-time posture change reached 99.9% (1 319/1 320), and no adverse event occurred. Within 2 days of admission, the lowest levels of PaO2 and PaCO2 of the patients were (100±19) and (42±4) mmHg, respectively, and the number of patients with mild, moderate, and severe ARDS were 10, 2, and 3, respectively, and none of the patients had oxygenation index>300 mmHg. On the 30th day of admission, the lowest levels of PaO2 and PaCO2 of the patients were (135±28) and (37±8) mmHg, respectively, 3 patients developed moderate ARDS, 1 patient developed severe ARDS, and 11 patients had oxygenation index>300 mmHg. Conclusions: The introduction of feedforward control theory in the treatment of rollover bed of mass patients with burn-explosion combined injury can ensure safe and successful completion of turning over with the rollover bed, promote the repair of burn wound, and improve respiratory function, and therefore improve the treatment quality of patients.
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Feminino , Humanos , Masculino , Gasometria , Queimaduras/terapia , Explosões , Síndrome do Desconforto Respiratório do Recém-Nascido , Estudos RetrospectivosRESUMO
Objective:To investigate the risk factors related to urinary tract infection after indwelling ureteral D-J tube in pregnant women with acute renal colic.Methods:Clinical data of 109 pregnant women with acute renal colic undergoing indwelling ureteral D-J tube in emergency department of Taizhou Hospital or Enze Hospital from January 2008 to December 2019 were retrospectively analyzed. There were 31 cases (28.4%) with urinary tract infection after discharge and before delivery (infection group) and 78 cases without infection (non-infected group). Univariate and multivariate logistic regression analyses were used to evaluate the risk factors of urinary tract infection after ureteral D-J tube insertion.Results:In 109 patients the average age was 28 (25,33) years, the average gestational age was 26 (21,31)weeks, and the average body mass index (BMI) was 24.84 (22.60,27.43) kg/m 2. Compared with the non-infected group, the infection group had a higher rate of positive urine culture [38.7%(12/31) vs. 15.4%(12/78), χ2=6.56, P=0.010] and diabetes [45.2%(14/31) vs. 11.5%(9/78), χ2=13.86, P<0.001], and a lower gestational age [23(20,28) vs.27(21,32) weeks, Mann-Whitney U test, P=0.006]. Multivariate analysis showed that diabetes( OR=7.739,95 %CI:2.579-23.223, P<0.001), positive urine culture( OR=3.249,95 %CI:1.131-9.330, P=0.029), and gestational age( OR=0.201,95 %CI:0.042-0.955, P=0.044) were independent risk factors for urinary tract infection in pregnant women with acute renal colic after ureteral D-J tube insertion. Conclusion:History of diabetes, gestational age, and positive preoperative urine culture are risk factors for urinary tract infection after ureteral D-J tube insertion in pregnant women with acute renal colic.
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Stereotactic biopsies for lesions in the brainstem and deep brain are rare. This study aimed to summarize our 6-year experience in the accurate diagnosis of lesions in the brain stem and deep brain and to discuss the technical note and strategies. From December 2011 to January 2018, 72 cases of intracranial lesions in the brainstem or deep in the lobes undergoing stereotactic biopsy were retrospectively reviewed. An individualized puncture path was designed based on the lesion's location and the image characteristics. The most common biopsy targets were deep in the lobes (43 cases, 59.7%), including frontal lobe (33 cases, 45.8%), temporal lobe (4 cases, 5.6%), parietal lobe (3 cases, 4.2%), and occipital lobe (3 cases, 4.2 %). There were 12 cases (16.7%) of the brainstem, including 8 cases (11.1%) of midbrain, and 4 cases (5.6%) of pons or brachium pontis. Other targets included internal capsule (2 cases, 2.8%), thalamus (3 cases, 4.2%), and basal ganglion (12 cases, 16.7%). As for complications, one patient developed acute intracerebral hemorrhage in the biopsy area at 2 h post-operation, and one patient had delayed intracerebral hemorrhage at 7 days post-operation. The remaining patients recovered well after surgery. There was no surgery-related death. The CT-MRI-guided stereotactic biopsy of lesions in the brainstem or deep in the brain has the advantages of high safety, accurate diagnosis, and low incidence of complications. It plays a crucial role in the diagnosis of atypical, microscopic, diffuse, multiple, and refractory lesions.
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Humanos , Encéfalo/diagnóstico por imagem , Técnicas Estereotáxicas , Biópsia , Tronco Encefálico/diagnóstico por imagem , Estudos Retrospectivos , Biópsia Guiada por ImagemRESUMO
Seven compounds were isolated from the alcohol extract of Edgeworthia gardneri by various technologies, including silica gel, Sephadex LH-20 and high performance liquid chromatography, and were identified as edgeworthiaside A (1), 2,4,6-trichlorol-3-methyl-5-methoxy-phenol 1-O-β-D-glucopyranosyl-(1-6)-β-D-glucopyranoside (2), 2,6-dimethoxy-4-(2-propen-1-yl)phenyl 6-O-(6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranoside (3), eugenol rutinoside (4), tiliroside (5), edgeworoside C (6), and salicylic acid (7). Compound 1 is a new chlorophenyl glycoside and 2-4 were isolated for the first time from Edgeworthia gardneri. The in vitro inhibition of α-glucosidase showed that the inhibition rate of compounds 1 and 2 were similar to acarbose.
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Objective:To observe the affected elbow flexor activities and balance of stroke patients in standing and walking as fixing the affected upper extremity with different methods. Methods:From September to December, 2018, 14 stroke patients from Affiliated Suzhou Science & Technology Town Hospital of Nanjing Medical University were included. They were measured elbow flexor contraction ratio (integrated electromyogram of flexor/integrated electromyogram of antagonist) with wireless surface electromyography as standing and walking in normal speed, and sway index with Biodex as standing, in four conditions: the affected arm without fixing, and fixed with elbow orthosis, and with unaffected hand backwards and forwards. Results:The contraction ratio was the most as the arm fixed with elbow orthosis in both standing and walking (F > 2.687, P < 0.05). The sway index was the most as the arm fixed with unaffected hand forwards (F = 21.091, P < 0.05). Conclusion:The elbow orthosis restraint may lead to increased contraction of the affected elbow flexor, which is unsatisfactory to inhibit flexor activity of the upper extremities; while restraint of unaffected hand forwards may lead to instable balance.
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Objective:To investigate the effect of body weight-supported treadmill training on neuropathic pain and expression of glutamate decarboxylase-65/67 (GAD-65/67) in spinal dorsal horn of rats with spinal cord injury (SCI). Methods:A total of 24 Sprague-Dawley rats were randomly divided into sham group, SCI-sedentary (SCI-Sed) group and SCI-Exercise (SCI-Ex) group, with eight rats in each group. Allen's method was used to make T10 incomplete SCI model. Seven days after SCI, SCI-Ex group was given body weight-supported treadmill training. Before SCI, and seven days, 14 days, 21 days, 28 days and 35 days after SCI, the von Frey filaments and thermal stimulation pain tester were used to evaluate the mechanical and thermal pain thresholds. Then, Western blotting and immunohistochemical analysis were performed on the spinal cord of all rats to detect the expression of GAD-65 and GAD-67. Results:The mechanical and thermal pain thresholds were higher in SCI-Ex group than in SCI-Sed group 21 days, 28 days and 35 days after SCI (P < 0.01). Compared with the sham group, the expression of GAD-65 and GAD-67 decreased in SCI and SCI-Ex groups (P < 0.05), and increased in SCI-Ex group compared with that of SCI-Sed group (P < 0.05). Conclusion:Body weight-supported treadmill training could increase the synthesis of GAD-65/67 in the distal spinal cord dorsal horn of incomplete SCI rats, and improve the pain thresholds of hind limbs in rats with SCI.
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Objective:To explore the therapeutic effect of Fuzheng Huayu capsule on nonalcoholic fatty liver fibrosis induced by high trans fatty acid and high sugar diet in mice. Method:Forty SPF male C57/B6 mice were randomly divided into 4 groups (normal group, model group, Obelcholinic acid group, and Fuzheng Huayu capsule group), with 10 mice in each group. Except 10 mice in the normal group, nonalcoholic fatty liver fibrosis was induced by high-fat and high-sugar diet for 24 weeks in the other 30 mice. From the 25th week of modeling, 4 groups received intragastric administration for 4 weeks, once a day: Fuzheng Huayu capsule group 4.8 g·kg<sup>-1</sup>. Oxycholic acid group 10 mg·kg<sup>-1</sup>. Model control group and normal group received the same volume of normal saline. Liver tissue and serum samples were collected at the end of the 28th week. The pathological changes of liver tissue of mice in each group were observed by hematoxylin-eosin (HE) staining, the degree of liver fibrosis was observed by Sirius red staining, the degree of lipid deposition was observed by oil red O staining, the content of hydroxypropylamine (Hyp) in liver tissue was determined by alkaline hydrolysis, and the change of triglyceride (TG) in liver tissue was detected by enzyme method. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) activities and fasting blood glucose (FBG) were detected by kit method, enzyme-linked immunosorbent assay (ELISA) was used to detect fasting Insulin (INS) level and calculate the changes of insulin resistance index (HOMA-IR), liver fibrosis related mRNA and proteins of were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), Western blot and Immunohistochemistry. Result:Compared with the normal group, the liver tissue in the model group showed significant collagen fiber deposition, at mostly F2-F3 fibrosis stages, with increased number of inflammatory foci in liver tissue, obvious balloon degeneration and fatty degeneration of liver cells, significantly increased contents of Hyp and TG in liver tissue (<italic>P</italic><0.01), significantly increased activities of ALT and AST in serum and levels of FBG, INS and HOMA-IR (<italic>P</italic><0.01), and increased type I collagen (Col-Ⅰ), Col-Ⅳ, <italic>α</italic>-smooth muscle agonist protein (<italic>α</italic>-SMA) and transforming growth factor-<italic>β</italic> (TGF-<italic>β</italic>) protein and mRNA in liver tissue. Compared with the model group, the collagen fiber deposition in liver tissue of mice in Fuzheng Huayu capsule group was significantly reduced, at mostly F0-F1 fibrosis stages, with significantly improved balloon-like change of hepatocytes, and significantly reduced number of inflammatory foci in lobules (<italic>P</italic><0.05,<italic>P</italic><0.01). Compared with the model group, Fuzheng Huayu capsule can significantly reduce the content of Hyp in liver tissue, the levels of serum ALT and AST, and the expression of Col-Ⅰ, Col-Ⅳ, <italic>α</italic>-SMA and TGF-<italic>β</italic> genes and proteins in mice (<italic>P</italic><0.05,<italic>P</italic><0.01). Conclusion:Fuzheng Huayu capsule has a good therapeutic effect on nonalcoholic fatty liver fibrosis induced by high trans fatty acid and high sugar diet in mice.
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Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) is an imaging method that uses magnetic resonance technology to perform objective, quantitative, and noninvasive assessment of fat in the whole liver. This article mainly analyzes the correlation between MRI-PDFF value and the “gold index” nonalcoholic steatohepatitis (NASH) liver histological evaluation and explores its advantages and disadvantages as a noninvasive evaluation index for NASH clinical trials. Current studies have shown that MRI-PDFF, as an emerging noninvasive technique, is suitable for quantifying liver fat content and evaluating the degree of hepatic steatosis, but it cannot replace liver biopsy as a tool for the diagnosis of NASH. Meanwhile, the relative reduction in MRI-PDFF after drug intervention is not only highly correlated with the improvement of fat deposition, but also correlated with the improvement of inflammation and ballooning degeneration, and MRI-PDFF can predict the overall improvement of liver histology to a certain extent. Therefore, MRI-PDFF is considered a potential surrogate endpoint for NASH clinical trials.
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OBJECTIVE@#To analyze the literature of acupuncture and moxibustion for diseases in the recent 5 years, and discuss the spectrum and indications of acupuncture and moxibustion.@*METHODS@#The literature on acupuncture and moxibustion for diseases in CNKI, Wanfang and VIP databases from January 1, 2015 to December 31, 2019 was searched, summarized and analyzed, and the disease spectrum was summarized. At the same time, the literature from 2015 to 2019 (group A), 1978 to 2005 (group B), and 1949 to 2005 (group C) was compared, and the indications of acupuncture and moxibustion therapy were summarized.@*RESULTS@#There were 32 011 articles on acupuncture and moxibustion for diseases in the recent 5 years, including 377 kinds of indications. These indications can be mostly classified as neurology (9384), orthopedics and traumatology (7765), gastroenterology (3529) and obstetrics and gynecology (2283). The types of diseases were mostly gastroenterology (52 types), neurology (47 types), ophthalmology and otorhinolaryngology (47 types), and obstetrics and gynecology (42 types). The first-class indications of acupuncture and moxibustion therapy in the recent 5 years were hemiplegia, lumbar disc herniation, cervical spondylosis, knee osteoarthritis, insomnia, constipation and cerebrovascular diseases; the second-class were facial neuritis, shoulder pain and headache; the third-class were dysphagia, dysmenorrhea and depression; the forth-class were asthma, urinary retention, cerebral palsy, hypertension, dementia, side effects of radiotherapy and chemotherapy, infertility, allergic rhinitis, vertigo, shoulder-hand syndrome, diabetic neuropathy, herpes zoster, pain, hiccup, diarrhea, lumbar sprain and sciatica.@*CONCLUSION@#Although the disease spectrum and indications of acupuncture and moxibustion therapy have changed to some extent in the recent 5 years, neurology and orthopedics and traumatology are still predominant, and the observation objects tend to transition from symptoms to diseases.
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Feminino , Humanos , Acupuntura , Terapia por Acupuntura , Bibliometria , Dismenorreia , MoxibustãoRESUMO
OBJECTIVE@#To describe the thyroid function abnormality of first-trimester twin pregnant women according to different references, and to explore its association with preterm delivery.@*METHODS@#Participants, first-trimester twin pregnant women, were recruited at Peking University Third Hospital from March 2017 to February 2020. The thyroid hormone reference for ordinary adults identified on the assay kits by Siemens incorporation, thyroid hormone reference specifically for singleton pregnancy established previously, and thyroid hormone reference specifically for twin pregnancy established previously were used in the description of hypothyroidism and hyperthyroidism for first-trimester twin pregnant women. Thyroid autoantibody reference identified on the assay kits by Siemens incorporation was used in the description of positive thyroid autoantibody. Multivariable log-binomial regression was conducted to examine the association between thyroid function and preterm delivery, in which normal pregnant women according to the three references and normal pregnant women according to twin pregnancy reference accompanied with negative thyroid autoantibody were taken as control respectively.@*RESULTS@#A total of 570 twin pregnant women were finally included. Rates of hypothyroidism according to the three references were 1.2%, 1.6% and 3.5%, respectively. Rates of hyperthyroidism according to the three references were 32.6%, 18.1% and 1.1%, respectively. After adjustment for potential confounding factors, risk of preterm delivery significantly increased in pregnant women with hyperthyroidism according to the twin specific pregnancy reference [adjusted relative risk (ARR)=1.41, 95%CI: 1.14-1.75], while no significant increase was found in those with normal thyroid function according to the twin specific pregnancy reference but hyperthyroidism according to the singleton specific pregnancy reference (ARR=1.00, 95%CI: 0.81-1.25) and in those with hyperthyroidism purely according to the ordinary adult reference (ARR=1.06, 95%CI: 0.85-1.32), compared with those normal according to all the references. Risks of preterm delivery almost significantly or significantly increased in pregnant women with hypothyroidism according to the ordinary adult or singleton specific pregnancy reference (ARR=1.40, 95%CI: 0.88-2.22) and those with hypothyroidism according to the twin specific pregnancy reference (ARR=1.53, 95%CI: 1.03-2.28). Overall analysis of thyroid function according to the twin specific pregnancy reference and thyroid autoantibody showed that risks of preterm delivery almost significantly or significantly increased in pregnant women with simple hypothyroidism (ARR=1.46, 95%CI: 0.93-2.27), simple positive thyroid autoantibody (ARR=1.32, 95%CI: 1.15-1.52), and hypothyroidism accompanied with positive thyroid autoantibody (ARR=1.78, 95%CI: 1.30-2.44), compared with those normal according to the twin specific pregnancy reference with negative thyroid autoantibody.@*CONCLUSION@#The ordinary adult reference and that of singleton pregnancy may lead to under-diagnosis of hypothyroidism and over-diagnosis of hyperthyroidism in first-trimester twin pregnant women. Compared with pregnant women with normal thyroid function, those missed in the diagnosis of hypothyroidism were at a higher risk of preterm delivery, while those over-diagnosed as hyperthyroidism had a similar risk of preterm delivery, indicating a need to develop and generalize twin-pregnancy-specific reference on common indicators of thyroid function. Moreover, the thyroid autoantibody should be taken into consideration in the prenatal diagnosis and treatment to twin pregnant women with hypothyroidism.
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Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Hipotireoidismo/epidemiologia , Complicações na Gravidez/epidemiologia , Primeiro Trimestre da Gravidez , Gestantes , Nascimento Prematuro/epidemiologiaRESUMO
Objective: To summarize the clinical application patterns in acupuncture-moxibustion treatment of AD by reviewing the clinical literatures on acupuncture-moxibustion for Alzheimer disease (AD) published between January 2009 and December 2019. Methods: China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP), Chinese Medicine Acupuncture-moxibustion Information Database, PubMed Medical Data Retrieval Service System, Springer Database and Ovid Technologies (OVID) were retrieved to screen clinical studies of acupuncture-moxibustion treatment of AD according to the inclusion and exclusion criteria to conduct quantitative, clustering and association analyses. Results: In acupuncture-moxibustion treatment of AD, the frequently used points were Baihui (GV 20), Zusanli (ST 36), Sishencong (EX-HN 1), Taixi (KI 3), Sanyinjiao (SP 6), and Neiguan (PC 6) in the descending order. Regarding meridians, the most frequently used one was the Governor Vessel, followed by the Stomach Meridian of Foot Yangming and Gallbladder Meridian of Foot Shaoyang. From the perspective of body regions, the points in the head-face region and the lower-limb region had the highest frequencies, followed by the upper-limb, back and chest-abdomen regions. The point group, Baihui (GV 20) and Sishencong (EX-HN 1)-Neiguan (PC 6)-Sanyinjiao (SP 6), showed the most significant association, and the group winning the second place was Baihui (GV 20) and Sishencong (EX-HN 1)-Neiguan (PC 6)- Zusanli (ST 36). The clustering analysis showed that the commonly used point pairs included Zusanli (ST 36)-Sishencong (EX-HN 1) and Taixi (KI 3)-Sanyinjiao (SP 6), which were closely associated with Baihui (GV 20). By analyzing the three commonly used acupuncture-moxibustion methods, acupuncture plus medication was found achieving the best result in the total effective rate and mini-mental state examination (MMSE) score, followed by monotherapy of electroacupuncture therapy, and these two methods were superior to acupuncture alone (P<0.05); the scores of MMSE, Alzheimer disease assessment scale-cognitive section (ADAS-cog) and activity of daily living scale (ADL) showed significant improvements after treatment (all P<0.01). Conclusion: In the acupuncture-moxibustion prescriptions for AD, the main points are Baihui (GV 20), Sishencong (EX-HN 1), Neiguan (PC 6), Zusanli (ST 36), Sanyinjiao (SP 6) and Taixi (KI 3). Monotherapy of acupuncture has the highest frequency amongst the treatment methods, but its effective rate is lower than that of acupuncture plus medication and monotherapy of electroacupuncture.
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Objective:Structure-based angiotension converting enzyme 2 (ACE2) and interleukin-6R (IL-6R) were taken as the target proteins to in the investigation of the material basis of Xuanfei Huazhuo prescription in the treatment of coronavirus disease-2019 (COVID-19) by molecular docking. Method:The compounds in Xuanfei Huazhuo prescription were retrieved through TCMSP. Structure-based ACE2 and IL-6R were taken as the target proteins to screen out the compounds with a better activity by molecular docking, and analyze structural properties of these compounds. Furthermore, the potential molecular mechanism of Xuanfei Huazhuo prescription in the treatment of COVID-19 was analyzed by target reverse prediction. Result:There were 312 potentially active compounds in Xuanfei Huazhuo prescription, including 75 highly active compounds and 15 highly active compounds for ACE2. There were 100 eligible active compounds and 3 highly active compounds for IL-6R, most of which belong to flavonoids. The herb-component-target network included 10 herbs, 126 compounds and 130 targets. String analysis showed that PIK3R1, SRC, AKT1, AR and EGFR might be the key targets of Xuanfei Huazhuo prescription. Conclusion:Based on the virtual screening of multi-target molecular docking, the anti-virus and anti-inflammatory material basis of Xuanfei Huazhuo prescription was preliminarily obtained. At the same time, based on the reverse prediction and analysis, potential targets and molecular mechanism of the recipe in the treatment of COVID-19 were explored, so as to provide clues for the multi-angle mining of Xuanfei Huazhuo prescription and its relevant prescriptions and the modernization development of monomer components.
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Objective To investigate the expression of miR-34a-5p and AKT1 genes in endometrium tissues of patients with endometriosis (EM) and their effects on migration and invasion of endometrial stromal cells (ESCs). Methods A total of 91 patients, undergone hysterectomy in the Department of Obstetrics and Gynecology of Zhujiang Hospital of Southern Medical University from Jan. 2018 to Jun. 2019 due to benign gynecological diseases, were collected and divided into EM group (68 cases) and non-EM group (23 cases). The expressions of miR-34a-5p and AKT1 genes in endometrium tissues of patients were detected by in situ hybridization and immunohistochemistry. ESCs were transfected with miR-34a-5p mimic and negative control RNA (miR-NC) using liposome-3000 to construct the cell models of miR-34a-5p mimic group and miR-NC group. The cell proliferation rate was detected by CCK-8 method, and cell migration, invasion, apoptosis and autophagy ability experiments were performed to determine the effect of miR-34a-5p on ESCs' proliferation, migration, invasion, apoptosis and autophagy. Results The positive expression rate of miR-34a-5p was lower, and of AKT1 was higher in EM group than those in non-EM group (16.2% vs. 82.6%, X2=34.323; 72.1% vs. 30.4%, X2=12.581, P<0.001). After culturing for 12, 24 and 48 h, the cell proliferation rate was higher in miR-NC group than that in miR-34a-5p mimic group (P<0.05). The cell migration ability and invasion ability were higher in miR-NC group than those in miR-34a-5p mimic group with statistically significant difference [(65.00%±5.00%) vs. (30.67%±4.04%); (88.0±8.5) vs. (32.3±6.1), t=9.179, P<0.05]. The cell apoptosis rate and the expression level of LC3 gene were obviously lower in miR-NC group than those in miR-34a-5p mimic group [(9.33%±3.51%) vs. (18.00%±2.00%); (0.19±0.04) vs. (0.39±0.03), t=8.02, P<0.05]. Conclusion miR-34a-5p may be involved in the pathogenesis of EM by targeting AKT1 genes to affect the proliferation, migration, invasion, apoptosis and autophagy function of ESC.
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Nonalcoholic fatty liver disease (NAFLD) and hypertension are both important components of metabolic syndrome, and there is a strong association between these two diseases. This article analyzes the association between NAFLD and hypertension based on clinical data and describes the common pathogeneses of the two diseases, among which insulin resistance, gut microbiota, renin-angiotensin-aldosterone system play an important role in the pathogenesis of these two diseases. In addition, this article briefly summarizes the application of renin-angiotensin-aldosterone system inhibitors and diuretics in the treatment of NAFLD, which provides a reference for further clarifying the association between these two diseases, understanding the mechanism of interaction between the two diseases, and exploring the treatment methods for NAFLD with hypertension.
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Lycophytes and ferns are unique and charismatic members of many terrestrial ecosystems and occupy the pivotal position in land plant origin and evolution. The Chinese lycophytes and ferns flora, with approximately 2000 species, contributes a substantial component to the global lycophytes and ferns diversity, with estimates of 12 000 species. Among them, about 433 species are medicinally recorded and researches based on their phytochemical properties are important topics in natural medicines. This paper reviewed the research history and current status of chemical constituents and biological activities of lycophytes and ferns, which had highlighted the research progress of our group.