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【Objective】 To explore the effectiveness of creating the obstructive sleep apnea hypopnea syndrome (OSAHS) animal model of glossocoma using the botulinum toxin type A in white rabbits, and to explore the effectiveness and safety of magnetic traction hyoid suspension operation in the OSAHS animal model of glossocoma. 【Methods】 A total of 12 adult male experimental white rabbits were randomly divided into two groups. The animals in the experimental group were injected with 0.4 mL (10 U) of botulinum toxin type A in the genioglossus muscle to construct the OSAHS animal model of glossocoma. The animals in the control group were injected with 0.4 mL of normal saline. We designed and 3D printed a polyacrylate shell that could be loaded with inner and outer neodymium iron boron (NdFeB) magnets. After the modeling, a polyacrylate shell with the inner magnet device was fixed on the hyoid bone of the animals in the experimental group. All animals in the experimental group wore the polyacrylate orthotic neck brace containing the outer magnet 10 days after the operation. The arterial blood oxygen detector was used to record the oxygen saturation (SaO2) of the femoral artery, and multi-slice CT plain scan was used to measure the diameter of the narrowest part of the upper airway. 【Results】 The animals in the experimental group gradually showed decreased activity, labored breathing, blue lips and ear margins and other manifestations of hypoxemia 5 days after intramuscular injection of botulinum toxin type A in the genioglossus, and their body weight dropped from (3.72±0.21)kg to (3.40±0.20)kg, the average SaO2 of the femoral artery decreased from (93.84±5.14)% to (84.00±3.35)%, and the diameter of the narrowest part of the upper airway decreased from (4.83±0.47)mm to (3.52±0.83)mm (P<0.05). In the control group, the animals’ weight, the average SaO2 of the femoral artery, and the diameter of the narrowest part of the upper airway did not significantly change before and after injection of normal saline into the genioglossus muscle (P>0.05). The animals in the experimental group completed the magnetic traction hyoid suspension surgery. After wearing the orthotic neck brace containing an external magnet for hyoid magnetic traction, the food intake and activity of the animals in the experimental group increased, the color of the lips changed from purple to pink, the SaO2 of the femoral artery increased significantly to (90.44±5.95)%, and the diameter of the narrowest part of the upper airway increased significantly to (4.42±0.15)mm (P<0.05). 【Conclusion】 The genioglossus muscle injection of botulinum toxin type A in white rabbits could successfully establish the OSAHS animal model of glossocoma. Magnetic traction hyoid suspension surgery in the treatment of OSAHS animal model could effectively correct the upper airway stenosis related symptoms and hypoxemia caused by glossocoma.
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【Objective】 To screen and verify a peptide ligand specific for CD44v9. 【Methods】 A 12-mer phage peptide library was screened on CD44v9 coated on solid phase. Candidate sequences emerged after sequencing. Candidate phages were selected using enzyme-linked immunosorbent assay. The best sequence was chosen for further study. Binding of C9-3 to CD44v overexpressed HEK-293 cells was determined using immunofluorescence. Binding affinity and specificity were verified on gastric cancer tissues with immunohistochemistry. 【Results】 Phages significantly were enriched during panning process. After sequencing, nine individual sequences occurred in 30 selected clones. Among the 9 candidate sequences, C9-3 exhibited the highest frequency. Results of ELISA showed that C9-3 had the highest OD value and selectivity. Thus, C9-3 was chosen for peptide probe synthesis. C9-3 probe stained CD44v overexpressed HEK-293 cells, but not empty vector transfected HEK-293 cells. Immunohistochemistry scores of C9-3 were significantly different between gastric cancer and paracancer tissues (t=3.953, P<0.01). A linear positive correlation was observed between C9-3 binding and CD44v9 expression (r=0.823, P<0.01). 【Conclusion】 In this study, peptide ligand of CD44v9 was successfully screened. The peptide can bind to cells and cancer tissues via CD44v9. It has potential for gastric targeting probes.
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【Objective】 To investigate the outcomes of intravenous injection of human albumin (HA) in patients with both liver cirrhosis and nephrotic syndrome. 【Methods】 We retrospectively studied 101 liver cirrhosis patients with ascites and nephrotic syndrome treated in our hospital from January 2018 to November 2021. All the patients received oral diuretic and intravenous albumin therapy. Their baseline characteristics were collected and the changes in serum albumin and creatinine levels before and after treatment were evaluated. The patients with elevated albumin levels after treatment greater than the median value (1.8 g/L) were defined as response group. The rest of the patients were classified as the non-response group. And Logistic regression analysis was used to evaluate the relevant influencing factors for treatment response. 【Results】 All the patients’ symptoms of abdominal distension related to moderate to great ascites were clinically lessened at the end of treatment, and no case of acute kidney injury occurred during the treatment. Of them, 32 patients had repeated hospitalizations within six months after discharge. The serum albumin level was significantly increased after treatment [(26.5±5.9) g/L vs. (29.9±4.9) g/L, P<0.001] and there was no significant difference in serum creatinine before and after treatment [(111.9±118.4)μmol/L vs. (108.5±87.9)μmol/L, P=0.816]. Fifty-three patients were defined as treatment response group. The differences in characteristics including age, sex, etiology of cirrhosis, and proteinuria were not statistically significant. However, the serum creatinine level was significantly lower in the response group than in the non-response group [(84.1±51.2)μmol/L vs. (142.7±158.4)μmol/L, P=0.017\]. A similar trend of difference was observed with respect to urea nitrogen level \[(8.7±5.1)mmol/L vs. (11.8±9.1)mmol/L, P=0.039\]. Multivariate analyses demonstrated that the serum creatinine level was a risk factor for non-response to treatment (hazard ratio=1.025, 95% CI: 1.010-1.049, P=0.037). In addition, the correlation analysis showed that the baseline albumin levels were negatively correlated with hospital stay time (r=-0.340, P=0.001), daily HA usage (r=-0.546, P<0.001), and baseline proteinuria levels (r=-0.654, P<0.001), respectively. 【Conclusion】 Intravenous injection of HA in cirrhotic patients with nephrotic syndrome was safe and effective for the treatment of ascites. Kidney function affects serum albumin levels and response to treatment.
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Immunotherapy has become another effective tumor treatment after surgical resection, chemotherapy, radiotherapy and targeted therapy. However, due to the low immunogenicity of tumor cells and immunosuppressive tumor microenvironment, antigen-presenting cells inefficiently process and present tumor antigens, thus leading to insufficient activation of cytotoxic T lymphocytes and tumor infiltration, which significantly affects the effectiveness of tumor immunotherapy. In recent years, it has been demonstrated that multiple metal ions exhibit distinguished modulatory effects in activating innate immune stimulation and conquering acquired immune tolerance. Based on this, scientists have designed a series of nano-adjuvant delivery systems with metal ions or metal nanoparticles to enhance the targeted accumulation of metal ions in tumor tissues or lymphoid organs for efficiently inducing immunogenic cell death or directly activating antigen-presenting cells to initiate anti-tumor specific immune response. This review briefly outlines the role of various metal ions in anti-tumor immunomodulation, summarizes the research progress in using metal nanoadjuvant delivery systems to achieve efficient anti-tumor immunotherapy, and provides foresight on the main challenges and potential directions in this field.
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Objective:To investigate the distribution and related factors of lipoprotein(a) [Lp(a)] level in healthy Tajik and Kazak adults in China.Methods:A cross-sectional study was conducted from May to October 2021 and March to June 2022, and blood samples were collected from 2, 637 healthy Tajik adults [1 010 men, average age: (40.08±14.74) years; 1 627 women, average age: (38.27±12.90) years] in Tashkurgan Tajik Autonomous County and 1 911 healthy Kazak adults [720 men, average age: (42.10±12.26) years; 1 191 women, average age: (38.27±12.90) years] in Fuyun County of Xinjiang. Fasting blood glucose (FBG), creatinine (Cr), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and Lp(a) were measured. The distribution of Lp(a) levels in different sex and age groups was compared. The Lp(a) level of Tajik and Kazakh ethnic groups was compared by Mann-Whitney U test, and correlation factors of Lp(a) level were analyzed by multiple logistic regression. Results:The distribution of Lp(a) level in Tajik and Kazak population was skewed. Lp(a) levels of Tajik and Kazak ranged from the lowest 0.40 mg/L and 0.62 mg/L to the highest 1 229.40 mg/L and 2 108.58 mg/L, respectively, and the median Lp(a) level was 78.90 (38.60, 190.20) mg/L and 103.30 (49.57, 234.27) mg/L, respectively. Median Lp(a) level of Kazak was significantly higher than that of Tjik ( P<0.001). The median Lp(a) levels of Tajik males and females were similar: 77.45 (39.80, 187.10) mg/L and 79.90 (38.60, 192.30) mg/L ( P=0.948). The median Lp(a) levels of Kazakh males and females were also similar: 109.42 (50.49, 230.38) mg/L and 99.01 (49.11, 237.25) mg/L, respectively ( P=0.578). After pooling the data of Tajik and Kazak and adjusting for age, sex, BMI, smoking, drinking, blood pressure, blood glucose and other factors, Lp(a) level was correlated with ethnic (standard partial regression coefficient 0.066, P=0.008) and LDL-C level (standard partial regression coefficient 0.136, P<0.001). Conclusions:Lp(a) level in healthy Tajik and Kazak adults varied greatly among individuals, and Kazak residents had a higher Lp(a) level than Tajik residents. There was no significant sex difference in Lp(a) level among Tajik and Kazakh, and LDL-C and ethnicity are independent factors related to Lp(a) level.
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Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.
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Objective:To evaluate the trend and hotspots of the research on cognitive frailty in China and abroad through literature visualization analysis.Methods:Literature related to cognitive frailty were retrieved from the databases of CNKI, Wanfang, VIP and Web of Science from January 1, 2013 to August 31, 2022 with"cognitive frailty""cognitive decline"and"cognitive impairment"as retrieval terms. Based on the visualization software CiteSpace and VOSviewer, the network map analysis was conducted on the number of publications, journal distribution, country distribution and cooperation, institution distribution and cooperation and research hotspots.Results:A total of 2 500 literatures were retrieved, including 151 in Chinese and 2 349 in English. The number of publications showed an increasing trend with time. Among Chinese journals, Chin J Mod Nurs published the most literature (10 articles), while BMC Geriatr published the most literature (105 articles) in English journals. The top 5 countries in the number of English literature published were the United States (608 articles), the United Kingdom (295 articles), Italy (271 articles), China (252 articles) and Canada (195 articles). The top 5 institutions in the number of Chinese literature published were Fudan University (12 articles), Capital Medical University (10 articles), Zhengzhou University (7 articles), Central South University (5 articles) and Huazhong University of Science and Technology (5 articles). The National Center For Geriatrics Gerontology in Japan published the most English articles (74 articles). A total of 22 Chinese keywords and 44 English keywords were included. The nodes of the network analysis diagram were closely connected and highly centralized. The Chinese and English keywords“cognitive frailty”“elderly”and“frailty”were all in the core position. The Chinese emergent words were“cognitive frailty”“heart failure”“chronic disease”and“risk prediction”. The English burst terms were“cognitive frailty”“questionnaire”“cohort study”“social isolation”and“prevention”. Conclusions:The research popularity in the field of cognitive frailty is increasing year by year, and the number of articles published in English is higher than those in Chinese. At present, the main research focus is cognitive frailty, the elderly and frailty with great differences between China and abroad.
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Objective:To evaluate the effect of two-way referral service in referral and treatment of patients with coronary disease.Methods:A non-randomized controlled study was used, 80 patients with coronary disease who were referred to the First Affiliated Hospital of Xinjiang Medical University through the fast referral channel, also called green referral channel (GRC) of telemedicine service mode from January 2021 to January 2022 were selected as the GRC referral group. A propensity score was used to match 110 patients from the same period with coronary disease who were referred to this hospital through conventional medical channels and had similar basic conditions such as age, gender, region and medical insurance type as the conventional referral group. The differences in disease severity, referral time, hospitalization cost and other indicators were compared using t-test, χ2 test and nonparametric test between the two groups, and the satisfaction of the GRC referral group was investigated. Results:The proportion of patients with heart function grade Ⅲ (NYHA grading), heart failure, atrial fibrillation and interventional therapy in the GRC referral group was significantly higher than conventional referral group (all P<0.05). The total referral time and bed waiting time of patients in the GRC referral group were significantly shorter than conventional referral group [14.16 (9.62, 25.61) vs 34.39 (28.51, 49.68) h, 2.13 (0.83, 6.64) vs 24.58 (20.27, 27.68) h] ( Z=8.465, 9.172, all P<0.001). The hospitalization cost, surgical treatment cost and material cost in GRC referral group were significantly higher than conventional referral group [24 755 (11 559, 56 521) vs 14 700 (9 375, 29 534) CNY, 6 013 (2 096, 8 256) vs 2 562 (2 044, 6 154) CNY, 12 093 (1 267, 35 689) vs 1 329 (826, 16 125) CNY] ( Z=2.814, 2.917, 3.353, all P<0.05), and the diagnosis cost was significantly lower than conventional referral group [4 878 (3 628, 6 847) vs 5 719 (4 228, 7 639) CNY] ( Z=2.323, P<0.05). In the GRC referral group, the satisfaction rates with referral process, visit time and patient experience were all above 90%. Conclusion:Two-way referral service based on telemedicine has a good application effect in the referral and treatment of patients with coronary disease.
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Objective @#To examine the association between acute exposure to traffic-related air pollutants (TRAP) NOX and NO2 and outpatient visits of pediatric respiratory diseases. @*Methods @#Data regarding outpatient visits to Department of Respiratory Diseases of Beijing Children's Hospital from 2015 to 2020 were collected, and the concentrations of nitrogen oxides (NOX), nitrogen dioxide (NO2) and other TRAP were collected from the surveillance sites assigned by the Peking University Health Science Center. A time-stratified case-crossover design was employed, and a conditional logistic regression model was created to examine the association between NOX and NO2 acute exposure and outpatient visits of pediatric respiratory diseases. @*Results @#The daily mean outpatient visits of pediatric respiratory diseases were 571 (interquartile range, 554) person-times among children at ages of 0 to 14 years in Beijing Children's Hospital from 2015 to 2020, and the daily mean outpatient visits for upper respiratory tract infections (URI), bronchitis, and pneumonia were 265 (interquartile range, 282), 143 (interquartile range, 178) and 128 (interquartile range, 120) person-times, respectively. The daily mean concentrations of atmospheric NOX and NO2 were 67.8 (interquartile range, 50.7) and 49.3 (interquartile range, 30.7) μg/m3, respectively. Conditional logistic regression analysis showed the largest lagged effect of NOX and NO2 on pediatric respiratory diseases at cumulative lags of 0 to 7 days. An increase in NOX concentrations by an interquartile range resulted in the excess risks of URI, bronchitis and pneumonia by 6.87% (95%CI: 6.37%-7.38%), 7.25% (95%CI: 6.51%-7.99%), and 5.51% (95%CI: 4.69%-6.33%), and an increase in NO2 concentrations by an interquartile range resulted in excess risks of URI, bronchitis and pneumonia by 5.71% (95%CI: 5.12%-6.31%), 5.32% (95%CI: 4.51%-6.14%), and 4.83% (95%CI: 3.91%-5.75%), respectively. NOX and NO2 presented a more remarkable effect on outpatient visits of pediatric respiratory diseases among children at ages of over 5 years. @*Conclusion @#NOx and NO2 acute exposure may increase the outpatient visits of pediatric respiratory diseases.
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Hepatic alveolar echinococcosis (HAE) is a parasitic disease caused by Echinococcus multilocularis infection and has wide distribution and great harm in China. At present, ultrasound, CT, and MRI are the main radiological examination methods for HAE, with certain limitations in preoperative diagnosis and evaluation. This article introduces the guiding effect of three-dimensional visualization technique and its derivative technologies in the accurate diagnosis and preoperative evaluation of HAE, so as to provide help for the clinical diagnosis and treatment of HAE in the future.
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ObjectiveTo analyze the polarized light microscopic characteristics， the composition of physical phases and their relative contents of Maifanitum from different origins， and to establish the Fourier characteristic fingerprint of Maifanitum powder crystals by X-ray diffraction（XRD）. MethodA total of 26 batches of Maifanitum samples were selected， and the microscopic characteristics of the sample powders and grinding flakes were observed by polarized light microscopy under single polarized light and orthogonal polarized light， and the main phase compositions and their relative contents were analyzed by powder crystal XRD technique， and the XRD Fourier characteristic fingerprint of Maifanitum was established. The incident light source of XRD was Cu target Kβ radiation， the light tube voltage and light tube current were 40 kV and 40 mA， respectively， the divergence slit was 1°， the scattering slit was 1°， the receiving slit was 0.2 mm， the scanning speed was 5°·min-1 with continuous scanning and scanning range of 5-90°（2θ）， and the step length was 0.02°. ResultThe polarized light micrographs of powders and grinding flakes of Maifanitum were obtained， and the main phases were plagioclase， potassium feldspar and quartz， and a few samples also contained illite， pyrite， iron dolomite， calcite， iron amphibole and chlorite， etc. The relative total content of feldspar phases was 61.9%-82.4%， and the relative content of quartz was 12.6%-33.6%. The XRD Fourier fingerprint analysis method of Maifanitum with 13 common peaks as the characteristic fingerprint information was established， and the similarity calculated by the mean correlation coefficient method was 0.920 9-0.997 7， the similarity calculated by the mean angle cosine method was 0.940 5-0.998 4， the similarity calculated by the median correlation coefficient method was 0.921 1-0.997 5， and the similarity calculated by the median angle cosine method was 0.947 5-0.998 2. ConclusionThe polarized light microscopic identification characteristics of Maifanitum are mainly plagioclase， quartz and potassium feldspar， and the technique of powder crystal XRD Fourier fingerprint analysis can be used for the identification of Maifanitum.
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Nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), is a common hepatic manifestation of metabolic syndrome. However, there are no effective therapy to treat this devastating disease. Accumulating evidence suggests that the generation of elastin-derived peptides (EDPs) and the inhibition of adiponectin receptors (AdipoR)1/2 plays essential roles in hepatic lipid metabolism and liver fibrosis. We recently reported that the AdipoR1/2 dual agonist JT003 significantly degraded the extracellular matrix (ECM) and ameliorated liver fibrosis. However, the degradation of the ECM lead to the generation of EDPs, which could further alter liver homeostasis negatively. Thus, in this study, we successfully combined AdipoR1/2 agonist JT003 with V14, which acted as an inhibitor of EDPs-EBP interaction to overcome the defect of ECM degradation. We found that combination of JT003 and V14 possessed excellent synergistic benefits on ameliorating NASH and liver fibrosis than either alone since they compensate the shortage of each other. These effects are induced by the enhancement of the mitochondrial antioxidant capacity, mitophagy, and mitochondrial biogenesis via AMPK pathway. Furthermore, specific suppression of AMPK could block the effects of the combination of JT003 and V14 on reduced oxidative stress, increased mitophagy and mitochondrial biogenesis. These positive results suggested that this administration of combination of AdipoR1/2 dual agonist and inhibitor of EDPs-EBP interaction can be recommended alternatively for an effective and promising therapeutic strategy for the treatment of NAFLD and NASH related fibrosis.
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Objective:To analyze the clinical characteristics and prognostic factors of high-risk neuroblastoma (HR-NB) patients with skeletal metastasis.Methods:The clinical features of 336 newly treated HR-NB patients with skeletal metastases admitted to the Department of Medical Oncology of Beijing Children′s Hospital, Capital Medical University from January 2007 to December 2018 were analyzed retrospectively.Kaplan-Meier method was used for the survival analysis, and Log- Rank test was used for univariate prognosis analysis.The Cox model was used to analyze the multifactorial prognostic analysis. Results:A total of 336 HR-NB patients were recruited, involving 188 males and 148 females with the median age of onset of at 43 (4-148) months.Skeletal metastases affected the viscerocranium (89 cases, 26.5%), neurocranium (193 cases, 57.4%), vertebrae (298 cases, 88.7%), sternum and ribs (183 cases, 54.5%), pelvis (270 cases, 80.4%), upper limbs (182 cases, 54.2%) and lower limbs (240 cases, 71.4%). The 5-year event-free survival (EFS) rate and overall survival (OS) rate were (30.4±2.7)% and (41.3±2.9)%, respectively.Univariate analysis showed a significantly lower 5-year OS rate in skeletal metastatic HR-NB patients with poor prognostic classification, the morphology of neuroblastoma (stroma-poor) and ganglioneuroblastoma (intermixed), high index of mitosis-karyorrhexis index, lactate dehydrogenase≥587 U/L, serum ferritin≥92 μg/L, MYCN amplification and 1p loss of heterozygosity, and metastases in the viscerocranium, neurocranium, vertebrae, sternum and ribs, pelvis, upper limbs and lower limbs (all P<0.05). The 5-year OS rate of HR-NB patients with all 7 regions of skeletal metastases was only (14.2±5.9)%, which was significantly lower than that in patients with a single region metastasis or multi-region metastases[(66.0±10.2)% vs.(43.6±3.4)%, χ2=45.722, P<0.05]. Cox multifactorial analysis showed that MYCN amplification ( HR=4.165, 95% CI: 2.356-7.363) and the viscerocranium metastasis ( HR=2.560, 95% CI: 1.519-4.315) were the independent risk factors affecting the prognosis of HR-NB patients with skeletal metastases (all P<0.05). Conclusions:The prognosis is extremely poor in HR-NB patients with multiple skeletal metastases at the initial diagnosis.The amplification of MYCN and the viscerocranium metastasis are the poor prognostic factors for HR-NB patients with skeletal metastases.
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MicroRNAs (miRNAs) are a class of small, single-stranded non-coding RNAs that act as important regulators of gene expression and are involved in a number of important processes in life. A large number of studies have suggested that dysregulation of miRNA expression may be an important part of the mechanism of human tumorigenesis and progression. MiR-155-5p is mainly regarded as an oncomiR that acts on multiple target genes to participate in tumor progression, although it has been suggested to possess cancer growth suppressor effects. In this paper, we summarize the effects of miR-155-5p on cancer cell proliferation, invasion, migration, and drug resistance in various tumor types and elucidate its value as a possible potential marker in assisting diagnosis.
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Objective: To explore the effects of fecal microbiota transplantation (FMT) on neurobehavior and gut microbiota of arsenic-exposed offspring rats. Methods: In April 2021, Thirty-six SPF SD rats aged 8 weeks were seleted, rats were ranked by weight and divided into four groups according to randomized block design, namely control group, arsenic exposure group (As group) , arsenic+normal saline group (As+NaCl group) and As+FMT group, 6 females and 3 males in each group. Fecal microbiota fluid were provided by feces of rats in control group. Rats drank tap water containing 75 mg/L sodium arsenite for one week and then were caged together. The arsenic exposure was terminated until the pups were born. Female rats with vaginal plug were treated with fecal microbiota fluid via gavage during neurodevelopmental teratogenic window period. The volume of gavage was 1 ml/100 g with once every two days, for a total of three times. Weight alterations of offspring rats were recorded every week after weaning, and when offspring rats grew up for 6 weeks, Morris test and open field experiment was used to observe learning and memory abilities, as well as neurobehavioral performance of autonomous exploration and tension, respectively. 16S rDNA sequencing technology was used to detect microbiota diversities in fecal samples of rats in As group and As+FMT group. Results: Compared with the control group, the ratio of swimming distance and staying time in the target quadrant and the times of crossing the platform of rats in As group decreased significantly, and the motor distance, times entering central zone and the number of grid crossing of rats decreased significantly (P<0.05) . Compared with As group, the ratio of swimming distance in target quadrant, the motor distance in central zone and times entering central zone of rats in As+FMT group were evidently increased (P<0.05) . The analysis of fecal microbiota diversities showed that, at the phyla level, the relative abundance of Bacteroidetes in feces of rats in As+FMT group was higher than that in As group (68.34% vs 60.55%) , while the relative abundance of Firmicutes was lower than that in As group (28.02% vs 33.48%) . At the genus level, the relative abundance of Prevotella in As+FMT group was significantly higher than that in As group, becoming the dominant genus (42.08% vs 21.78%) . Additionally, compared with As group, a total of 22 genus were increased with 21 decreased genus in As+FMT group (P<0.05) . LEfSe analysis showed that dominant genuses in As+FMT group were Prevotella and UCG_005, and their relative abundance was significantly higher than that of As group (P<0.05) . Conclusion: FMT may alleviate the impaired learning and memory ability and anxiety like behavior of the offspring rats exposed to arsenic, and improve the disrupted gut microbiota.
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Masculino , Ratas , Animales , Femenino , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Arsénico , Ratas Sprague-Dawley , HecesRESUMEN
Hair loss affects millions of people at some time in their life, and safe and efficient treatments for hair loss are a significant unmet medical need. We report that topical delivery of quercetin (Que) stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice. We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1α in endothelial cells. Skin administration of a HIF-1α agonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que. Together, these findings provide a molecular understanding for the efficacy of Que in hair regrowth, which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine, and suggest a route of pharmacological intervention that may promote hair regrowth.
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Ratones , Animales , Quercetina/farmacología , Células Endoteliales , Cabello , Folículo Piloso , AlopeciaRESUMEN
Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.
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Animales , Humanos , Sarcopenia/metabolismo , Proteína Forkhead Box O3/metabolismo , Músculo Esquelético/metabolismo , Envejecimiento/metabolismo , Primates/metabolismoRESUMEN
Objective: To observe the effect of Tuina (Chinese therapeutic massage) on creatine kinase (CK), mitochondrial Ca2+ concentration, and ultrastructure of skeletal muscle in delayed onset muscle soreness (DOMS) model rats.Methods: A total of 130 healthy male Sprague-Dawley rats were randomly divided into a blank group, an exercise control group, a pre-exercise Tuina group, and a post-exercise Tuina group. According to the time points for sample collection, the exercise control group was divided into a 0 h exercise control group, a 24 h exercise control group, a 48 h exercise control group, and a 72 h exercise control group; the pre-exercise Tuina group was further divided into a 0 h pre-exercise Tuina group, a 24 h pre-exercise Tuina group, a 48 h pre-exercise Tuina group, and a 72 h pre-exercise Tuina group; and the post-exercise Tuina group was divided into a 0 h post-exercise Tuina group, a 24 h post-exercise Tuina group, a 48 h post-exercise Tuina group, and a 72 h post-exercise Tuina group. Rats in all groups except for the blank group received DOMS modeling. Professionals performed Nie-Pinching manipulation and finger Nian-Twisting manipulation on the lower limbs of the rats. The samples were collected at 0 h, 24 h, 48 h, or 72 h after exhaustive exercise for each pre-exercise Tuina group. The samples were collected at 0 h, 24 h, 48 h, or 72 h after Tuina for each post-exercise Tuina group. The changes in serum CK, skeletal muscle mitochondrial Ca2+ concentration, and Ca2+-adenosine triphosphatase (ATPase) were determined. The ultrastructure changes of skeletal muscles in each group were observed by a transmission electron microscope. Results: The electron microscope showed that compared with the exercise control group, the skeletal muscle structures of the pre-exercise Tuina group and the post-exercise Tuina group were significantly improved, and the overall performance of skeletal muscle in the pre-exercise Tuina group was more similar to that of the blank group. The level of serum CK in the pre-exercise Tuina group and the post-exercise Tuina group was significantly lower than that in the exercise control group (P<0.01). The Ca2+ concentration of skeletal muscle in the 24 h, 48 h, and 72 h pre-exercise Tuina groups was lower than that in the post-exercise Tuina group at the same time point (P<0.01). The Ca2+-ATPase concentration of skeletal muscle in the 24 h and 72 h pre-exercise Tuina groups was lower than that in the post-exercise Tuina group at the same time point (P<0.05).Conclusion: Tuina effectively prevents muscle damage caused by heavy exercise and long-term exercise, which may be related to the increase of skeletal muscle Ca2+-ATPase activity and mitochondrial Ca2+ transport.
RESUMEN
OBJECTIVE@#To construct an adenovirus vector expressing artificial splicing factor capable of regulating alternative splicing of Yap1 in cardiomyocytes.@*METHODS@#The splicing factors with different sequences were constructed against Exon6 of YAP1 based on the sequence specificity of Pumilio1. The PCR fragment of the artificially synthesized PUF-SR or wild-type PUFSR was cloned into pAd-Track plasmid, and the recombinant plasmids were transformed into E. coli DH5α for plasmid amplification. The amplified plasmids were digested with Pac I and transfected into 293A cells for packaging to obtain the adenovirus vectors. Cultured neonatal rat cardiomyocytes were transfected with the adenoviral vectors, and alternative splicing of YAP1 was detected using quantitative and semi-quantitative PCR; Western blotting was performed to detect the signal of the fusion protein Flag.@*RESULTS@#The transfection efficiency of the adenovirus vectors was close to 100% in rat cardiomyocytes, and no fluorescent protein was detected in the cells with plasmid transfection. The results of Western blotting showed that both the negative control and Flag-SR-NLS-PUF targeting the YAPExon6XULIE sequence were capable of detecting the expression of the protein fused to Flag. The results of reverse transcription-PCR and PCR demonstrated that the artificial splicing factor constructed based on the 4th target sequence of YAP1 effectively regulated the splicing of YAP1 Exon6 in the cardiomyocytes (P < 0.05).@*CONCLUSION@#We successfully constructed adenovirus vectors capable of regulating YAP1 alternative splicing rat cardiomyocytes.
Asunto(s)
Animales , Ratas , Adenoviridae/metabolismo , Empalme Alternativo , Animales Recién Nacidos , Escherichia coli/metabolismo , Vectores Genéticos , Miocitos Cardíacos/metabolismo , Plásmidos , Factores de Empalme de ARN/metabolismo , TransfecciónRESUMEN
ObjectiveTo explore the accuracy of clinical common serum fibrosis indexes hyaluronic acid （HA）， type Ⅳ collagen （CⅣ）， laminin （LN）， and type Ⅲ procollagen peptide （PⅢNP）， in combination with liver stiffness measurement （LSM， measured by transient elastography） and non-invasive markers of fibrosis aspartate aminotransferase to platelet ratio index （APRI） and fibrosis-4 （FIB-4） in the prediction of the hepatic fibrosis of Wilson's disease （WD） and to observe the clinical effect of Gandouling （GDL）. MethodThe data of 76 WD patients were collected and the LSM， serum fibrosis indexes （HA， PⅢNP， CⅣ， LN）， APRI， and FIB-4 before treatment were recorded. The correlation of LSM with serum fibrosis indexes， APRI， and FIB-4 was discussed via Pearson′s correlation analysis. According to the therapeutic schemes， patients were classified into the control group （36 cases） and treatment group （40 cases）. Patients in control group were treated with sodium dimercaptopropylsulfonate （DMPS）， while those in the treatment group received GDL in addition to the western medicine therapy. The treatment lasted 6 courses （8 days/course） and the influence of GDL on the indictors was evaluated. ResultHA， CⅣ， LN， PⅢNP， APRI， and FIB-4 were in positive correlation with LSM （r=0.517， 0.438， 0.281， 0.457， 0.778， 0.847， P<0.01）. HA， CⅣ， LN， and PⅢNP in the treatment group were lower after treatment than before treatment （P<0.05， P<0.01）. HA， CⅣ， and LN in the control group were lower after treatment than before treatment （P<0.05， P<0.01）， and PⅢNP showed no significant difference. LSM， FIB-4， and APRI in both groups decreased after treatment （P<0.05）. After treatment， LSM， FIB-4， APRI， HA， and PⅢNP in the treatment group were lower than those in the control group （P<0.05， P<0.01）， but CⅣ and LN demonstrated no significant difference from the control group. ConclusionLSM in combination with serum fibrosis indexes （HA， PⅢNP， CⅣ， LN）， FIB-4， and APRI can help accurately identify the level of the hepatic fibrosis in WD. Moreover， on the basis of decoppering by western medicine， GDL can significantly improve the liver function and hepatic fibrosis of WD patients.