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Objective To summarize and analyze the clinical phenotypes,hereditary features and treatment and follow-up strategies of different hereditary pheochromocytoma/paragangliomas(PCC/PGL)and related syndromes.Methods Forty-four clinically diagnosed PCC/PGL patients admitted in our hospital from January 2000 to August 2022 were enrolled,and the clinical data of them and their family members were collected.Second-generation sequencing was performed on 43 patients for genetic detection,and Sanger sequencing was applied to verify the mutation of the probands and family members.Results There were 15 patients diagnosed with hereditary PCC/PGL,including 7 cases of von Hippel-Lindau(VHL)syndrome,3 cases of multiple endocrine neoplasia type 2(MEN2),and 5 cases of familial paraganglioma syndrome.Seven VHL syndrome families were diagnosed as VHL2A(c.500G＞A),VHL2B(c.239G＞T and c.444_457del),and VHL2C(c.293A＞G)according to their clinical manifestations.All probands received surgical treatment,and 2 cases of recurrent PCC and the patients with multiple renal cancer also received targeted therapy with sunitinib.Three MEN2 families carried c.1901G＞C,c.1832G＞A,and c.1901G＞A missense mutations,respectively,and were diagnosed with MEN2A clinically.All of them underwent adrenalectomy and thyroidectomy,including one for preventive thyroidectomy.Among the 5 familial paraganglioma syndrome families,4 patients carried SDHB mutations(SDHB:c.343C＞T,c.541-2A＞G,c.575G＞A,c.268C＞T)and 1 patient carried an SDHD mutation(SDHD:c.337_340del).Sporadic retroperitoneal PGL were most common.Conclusion More than 1/3 of PCC/PGL patients carry germline gene mutations,showing obvious genotype-phenotype correlation.Genetic diagnosis technology plays an important guidance role for clinical precision treatment and follow-up,and genetic counseling.
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Human physiological indicators have become an important standard for assessing health in modern society.Traditional detection methods often require a separate laboratory,complex operation process and long detection time,so it is urgent to develop portable,fast and accurate on-site detection technologies for bioanalysis.Point-of-care testing(POCT),which differs from traditional laboratory testing,can realize the rapid in situ detection of biomarkers without the complicated analytical process of the laboratory.Smartphones,which are an essential tool in our daily life,not only have independent operating systems and built-in storage functions,but also have high-definition cameras,which have great application potential in POCT visualization.The combination of various biosensing technologies and smartphones has developed into a new direction in the field of POCT.This review mainly introduced the research progress of smartphone-based visual biosensors in POCT in recent years,including colorimetric sensors,fluorescence sensors,chemiluminescence sensors and electrochemiluminescence sensors.Finally,the problems faced by smart-phone-based visual biosensors in the application of POCT were summarized,and their future development was prospected.
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90 patients(251 teeth)with wedge-shaped defects were included and randomly divided into the study group(45 patients with 125 teeth,treated with flowable resin filling)and the control group(45 patients with 126 teeth,treated with composite resin).The success rates were compared between the 2 groups.The results showed that the success rate of flowable resin was basically the same with that of com-posite resin,and the clinical operation time was shorter.
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Objective To develop an undergraduate curriculum for nursing engineering hence to provide a reference for establishing an innovative thinking of nursing undergraduates and cultivating innovative talents with interdisciplinary knowledge in nursing and engineering.Methods Based on literatures review,the primary undergraduate curriculum for nursing engineering was drafted through the expert focus method.With the Delphi method,20 experts were engaged in two rounds of correspondence consultation to finalise the curriculum.Results The response rate from two rounds of expert consultation was 100.00%,with an expert authority coefficient of 0.855.Of the first and second round of consultations,the coefficient of variation of each item was 0.09-0.28 and 0.08-0.24,respectively,and the Kendall coordination coefficient was 0.130-0.210 and 0.152-0.350,respectively(all P<0.01).The average importance of each item for the first round of consultation was 3.45 to 4.68,with a standard deviation from 0.51 to 1.14,and it was 3.80 to 4.85 for the second round with a standard deviation from 0.37 to 0.99.Finally,the undergraduate curriculum for nursing engineering was finalised.It included 4 primary indicators,10 secondary indicators and 38 tertiary indicators.Conclusions The developed undergraduate curriculum for nursing engineering meets the requirement of clinical medicine and development in nursing science.The curriculum is authoritative and scientific,therefore it can provide a reference for the training of innovative talents with interdisciplinary knowledge of nursing and engineering in China.
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Objective To observe the value of laparoscopic ultrasound(LUS)combined with CT three-dimensional reconstruction for guiding laparoscopic hepatectomy(LH).Methods Data of 78 hepatocellular carcinoma(HCC)patients who underwent LH were retrospectively analyzed.The patients were divided into observation group(n=46)or control group(n=32)based on whether underwent preoperative CT three-dimensional reconstruction and LUS.Clinical data,perioperative data and prognosis were compared between groups.Results No significant difference of clinical data was found(all P＞0.05),whereas significant differences of tumor body mainly location,resection method,tumor resection margin,surgical operation time,intraoperative blood loss,postoperative hospital stay,postoperative complication grading and incidence were found between groups(all P＜0.05).During follow-up period,15 patients died in observation group and 14 died in control group.Significant difference of disease-free survival rate was detected between groups(x2=4.210,P=0.040).Conclusion LUS combined with CT three-dimensional reconstruction for guiding LH could reduce intraoperative injury and complication incidence,improving disease-free survival rate of HCC patients.
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Bone and soft tissue tumors are diverse and with complicated histologic components and significantly divergent biological behaviors.Conventional imaging examinations,such as CT,magnetic resonance imaging(MRI)and positron emission tomography(PET),are limited to the identification of anatomical structures and abnormal signals,which are difficult to meet the qualitative requirements of imaging.With the improvement of digitalization in hospitals and medical institutions,the introduction of electronic medical records and the improvement of computational power,modern intelligent medical treatment gradually evolves to the combination of human brain,big data and artificial intelligence.Researchers are committed to mining deeper image data information,and radiomics came into being.Radiomics is a method of extracting and analyzing subvisual quantitative features from medical images and quantifying tumor heterogeneity through modeling,which is of great significance in the accurate diagnosis and treatment of bone and soft tissue tumors.
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Objective:To explore the clinical features of programmed cell death-1 (PD-1) inhibitor-associated hypophysitis and improve the understanding of the disease.Methods:For the present retrospective case series study, the clinical data of patients with PD-1 inhibitor-associated hypophysitis who were treated at the Affiliated Hospital of Hebei University and the 3rd Hospital of Hebei Medical University from January 2020 to May 2023 were collected for analysis of clinical manifestations and prognosis.Results:Fifteen cases of PD-1 inhibitor-induced hypophysitis were included, with 13 males and 2 females. The mean age of onset was (62.1±7.5) years, and the median time of onset was 6.5 (4.7, 11.6) cycles of PD-1 inhibitor. At diagnosis, 14 patients complained of gastrointestinal symptoms, and 12 patients complained of fatigue. There were 12, 1, 1, 5, and 1 cases of hyponatremia, hypokalemia, hypoglycemia, hypotension, and fever, respectively. Secondary adrenocortical insufficiency occurred in all cases. Moreover, four patients had secondary hypothyroidism, and two patients had secondary hypogonadism. Posterior pituitary hypofunction was not found. Pituitary MRI showed one case each of vacuolar sella turcica, pituitary cystic lesion, pituitary stalk slightly shifted to the left, high metabolism in the sella turcica, and pituitary abnormal signal, while no abnormalities were found in 11 cases. The follow-up time was (47.66±11.93) weeks. At the last follow-up, one patient′s serum levels of adrenocorticotropic hormone and cortisol returned to normal.Conclusions:Hypophysitis associated with PD-1 inhibitors occurs later, and gastrointestinal symptoms and fatigue are the most common clinical manifestations. PD-1 inhibitor-associated hypophysitis mainly manifests as adrenocortical hypofunction, and some cases manifest as hypothyroidism and hypogonadism. In addition, patients with PD-1 inhibitor-associated hypophysitis show no obvious imaging changes in the pituitary gland.
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ObjectiveTo observe the effect of salvianolate on the protein expressions of adenosine monophosphate （AMP）-activated protein kinase （AMPK）， silent information regulator 1 （SIRT1） and peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α）， autophagy and apoptosis in kidney tissue of rats with membranous nephropathy （MN）， and to explore its possible molecular mechanism against MN. MethodEighty male SD rats were randomly divided into normal group， model group， benazepril hydrochloride group （10 mg·kg-1）， and salvianolate low-， medium-， and high-dose groups （16.7， 33.3 and 66.7 mg·kg-1）. The rats were modeled by injection of cationized bovine serum albumin （C-BSA） into the tail vein. After successful modeling， rats in the administration groups were given corresponding doses of drugs for 4 consecutive weeks， and then 24-hour urine， serum and kidney tissue were collected for the detection of 24-hour urinary protein （UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， C reactive protein （CRP）， glutathione peroxidase （GSH-Px）， superoxide dismutase （SOD）， and malondialdehyde （MDA）. The pathological changes of kidneys were observed by light microscope， electron microscope and immunofluorescence. Western blot was used to detect the protein expressions of phospho-AMPK （p-AMPK）， AMPK， phospho-SIRT1 （p-SIRT1）， SIRT1 and PGC-1α in rat kidney tissue. The protein expressions of autophagy-specific gene （Beclin-1）， microtubule-associated protein 1 light chain 3 （LC3） Ⅱ， ubiquitin-binding protein （p62）， B cell lymphoma （Bcl-2）， Bcl-2-associated X （Bax）， and cysteine aspartic protease-7 （Caspase-7） in rat kidney tissue were determined by immunohistochemistry （IHC）. ResultCompared with the conditions in the normal group， the levels of UTP， IL-6， TNF-α， CRP and MDA in the model group were increased （P<0.05） while the levels of SOD and GSH-Px were decreased （P<0.05）， and there was no difference in BUN and SCr. Compared with the model group， the administration groups had lowered UTP， IL-6， TNF-α， CRP and MDA （P<0.05） while elevated SOD and GSH-Px （P<0.05）. It could be seen from hematoxylin and eosin （HE） staining， Masson staining， immunofluorescence and electron microscopy that the pathological damage of rat kidney tissue in the model group was significant， but after treatment with benazepril hydrochloride and salvianolate， the pathological damage of kidney cells was gradually improved. The expressions of p-AMPK/AMPK， p-SIRT1/SIRT1， PGC-1α， Bcl-2， Beclin-1 and LC3Ⅱ in rat kidney in the model group were lower than those in the normal group （P<0.05） while the expressions of Bax， Caspase-7 and p62 were higher （P<0.05）. Compared with the model group， benazepril hydrochloride group and salvianolate groups had an up-regulation in the expressions of p-AMPK/AMPK， p-SIRT1/SIRT1， PGC-1α， Bcl-2， Beclin-1 and LC3Ⅱ in the kidney （P<0.05） while a down-regulation in the expressions of Bax， Caspase-7 and p62 （P<0.05）. ConclusionThe protective effect of salvianolate on the kidneys of MN rats may be related to the activation of AMPK/SIRT1/PGC-1α signaling pathway， the up-regulation of autophagy and the reduction of apoptosis.
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Fifteen compounds were isolated from the 95% ethanol extract of the whole plant of Elephantopus tomentosus L. by silica gel column chromatography, Sephadex LH-20 column chromatography, MCI column chromatography and semi-preparative HPLC methods. Their structures were identified on the basis of physicochemical properties, and spectral data (UV, IR, NMR, MS and CD) analysis as tomenlephanlide A (1), molephantinin (2), molephantin (3), 8-O-methacryloylelephanpane (4), apigenin (5), tricin (6), 2-phenyl acetamide (7), 3,4-dihydroxybenzoic acid methyl ester (8), caffeic acid methyl ester (9), caffeic acid ethyl ester (10), (+)-(4S)-(2E)-4-hydroxy-2-nonenoic acid (11), E-4-hydroxyhex-2-enoic acid (12), 1H-indole-3-carboxylic acid (13), 1H-indole-3-carbaldehyde (14) and isohematinic acid (15). Among them, compound 1 is a new germacrene-type sesquiterpenoid, 5-15 were obtained from E. tomentosus L. for the first time. It was the first time the absolute configuration of compound 2 was reported. Compound 1 showed weak cytotoxicity against gastric cancer cells (SGC-7901).
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To study the material basis of cold and hot properties of traditional Chinese medicines (TCMs) in Lamiaceae and to establish a cold and hot properties identification model, a database of material components of TCMs in Lamiaceae was established. A three-level classification system of material components was used to obtain the material basis of cold and hot properties of the Lamiaceae family by using data mining methods such as frequency analysis, association rule analysis, logistic regression, and feature selection. Several identification models were established to recognize the cold and hot properties. The chi-square test results showed that the material composition ratios of cold and hot properties were significantly different at the first-level, second-level, and third-level classification (P < 0.05), and the differences varied as the levels of substance classification changed. The average coefficients of variation were 42.30%, 79.07%, and 91.51% at the first-level, second-level, and third-level classification levels, respectively. In other words, in terms of the percentage differences in material composition ratio, the first-level was smaller than the second-level, and the second-level was smaller than the third-level. The results of the association rule analysis showed that under the third-level classification, there were many effective association rules, and 27 core groups and 34 specific groups of chemical components were obtained based on these rules. 15 decisive groups were obtained from the feature selection results. Multinomial logistic regression analysis was used to successfully establish a cold and hot properties identification model with an overall accuracy of 89%. The material basis of cold and hot properties of TCMs in Lamiaceae is different and intersect with each other. Twenty-seven groups of chemical components, such as bicyclic diterpenes, are the core groups of cold and hot properties, of which 15 groups are the decisive groups. The cold and hot properties are often characterized by the interaction of multiple classes of substances, and a single class of substances often cannot be used to characterize the properties. The organic combination of multiple classes of substances is the material basis of cold and hot properties.
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Objective:To explore the status of microsatellite instability (MSI) and its relationship with clinicopathological characteristics of patients with endometrial carcinoma.Methods:The clinical data of 365 patients with endometrial carcinoma who received surgery in Shanxi Province Cancer Hospital between January 2020 and December 2021 were retrospectively analyzed. Immunohistochemistry was used to detect the expressions of 4 DNA mismatch repair (MMR) proteins (MLH1, MSH2, MHS6, and PMS2), estrogen receptor (ER), progesterone receptor (PR), and p53 mutant protein in postoperative cancer tissue samples from 365 patients with endometrial carcinoma. All patients were divided into MSI group (1 or more non-expression of MMR protein) and microsatellite stability (MSS) group (4 proteins were all expressed), and the clinicopathological characteristics of patients in both groups were compared. φ efficient was used to analyze the correlation of MSI with ER, PR, p53 mutant protein expressions. Results:There were 72 cases (19.7%) in MSI group and 293 cases (80.3%) in MSS group; and the age of all patients was (53±19) years (21-83 years). There were statistically significant differences in the proportion of MSI patients in endometrial carcinoma patients with different age [>50 years vs. ≤50 years: 22.1% (61/276) vs. 12.4% (11/89)], tumor diameter [≤2 cm vs. > 2 cm: 25.9% (30/116) vs. 16.8% (42/249)], International Federation of Gynecology and Obstetrics (FIGO) staging [stage Ⅲ-Ⅳ vs. stage Ⅰ-Ⅱ: 31.1% (14/45) vs. 18.1% (58/320)], histological type [type Ⅰ vs. type Ⅱ: 21.7% (71/327) vs. 2.6% (1/38)] (all P < 0.05). There were no statistically significant differences in the proportion of MSI patients with different depth of invasion, degree of differentiation, lymph node metastasis, vascular involvement, and lesion location (all P > 0.05). Among 327 cases of type Ⅰendometrial carcinoma, 1 case was mucinous adenocarcinoma (MSS status), and the other 326 cases were endometrioid adenocarcinoma. Of the 72 patients with MSI, 71 cases were endometrioid carcinoma and the other was 1 of 3 mixed carcinomas in type Ⅱ endometrial carcinoma. There was a negative correlation between MSI and mutant p53 ( φ coefficient was -0.11, P = 0.031), and φ coefficient of the correlation of MSI with ER and PR was -0.03 and -0.06, while there were no statistically significant differences ( P value was 0.578 and 0.255, respectively). Conclusions:Endometrioid adenocarcinoma is the main type of endometrial cancer patients with MSI. MSI in endometrial cancer is correlated with age, FIGO staging, tumor diameter and histological type of patients, while negatively correlated with mutant p53.
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ObjectiveBased on serum pharmacochemistry and ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） the transitional components in the serum of rats after intragastric administration of water extract of Alismatis Rhizoma（AR）and salt-processed Alismatis Rhizoma（SAR） were compared. MethodSD rats were randomly divided into blank group, AR group（10 g·kg-1） and SAR group（10 g·kg-1）, 3 rats in each group, the administration groups were given AR and SAR aqueous extracts by gavage, respectively, and the blank group was given an equal volume of drinking water by gavage once in the morning and once in the evening, for 3 consecutive days. Sixty minutes after the last administration, blood was collected from the eye orbits, and the serum samples were prepared. The serum samples were prepared on an ACQUITY UPLC BEH C18 column（2.1 mm×50 mm, 1.7 μm） with the mobile phase of acetonitrile（A）-0.1% formic acid aqueous solution（B） in a gradient elution（0-10 min, 10%-50% A; 10-27 min, 50%-95%A; 27-27.1 min, 95%-10% A; 27.1-30 min, 10%A）, the data were collected at a flow rate of 0.3 mL·min-1 in positive ion mode with a scanning range of m/z 100-1 200. Based on the self-constructed chemical composition library of AR, the total ion flow diagrams and secondary MS fragmentation information of the aqueous extracts of AR and SAR, as well as the administered serum and the blank serum, were compared with each other by UNIFI 1.9.2, so as to deduce the possible blood-migrating constituents and their cleavage patterns in the aqueous extracts, and the response intensity ratios of each chemical component were calculated before and after processing. ResultA total of 20 components, including 5 prototypical components and 15 metabolites, were analyzed and deduced from the serum of rats given aqueous extract of AR. And 14 components, including 5 prototypical components and 9 metabolites, were analyzed and deduced from the serum of rats given aqueous extract of SAR. Of these, 13 components were common to both of them, including 5 prototypical components and 8 metabolites. The 5 prototypical components were 16-oxoalisol A, alisol A 24-acetate, alisol A, alisol B and alisol C. The metabolites were mainly involved in phase Ⅰ metabolism（oxidation） and phase Ⅱ metabolism（glucuronidation）. There was a big change in the intensity of response of the common components before and after salt-processing, and the response intensities of the prototypical components, 16-oxoalisol A, alisol B and alisol C, were elevated, while the type and response intensity of metabolites were generally decreased, and it was hypothesized that the metabolic rate of terpenoids might be slowed down after salt-processing of AR, so that the blood-migrating constituents could participate in the metabolism of the body more in the form of prototypes. ConclusionSalt-processing of AR may promote the absorption of prototypical components into the blood by slowing down the metabolic rate of terpenoids, which can provide support for the research on material basis of AR and SAR.
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Objective To explore the effect of temperature on the risk of hand-foot-and-mouth disease (HFMD) and population susceptibility. Methods The data of HFMD cases in Chengdu from January 1, 2016 to October 31, 2022 were collected, and local meteorological data during the same period were also collected. Distributional lag nonlinear models were developed. The relative risk (RR) of morbidity at different temperatures and different lags was calculated. Differences in the relative risk levels of different populations were analyzed and compared. Results A total of 263 776 cases of HFDM were reported in Chengdu during the study period. The distribution of HFMD was periodic. For the overall population, the short-term average temperature and RR showed a “U”-shaped relationship. When the lag time was 0-7 days, the cumulative RR was 1.59 (95%CI: 1.18-2.14) at the average temperature of -0.5℃ and 2.16 (95%CI: 1.60-2.91) at the average temperature of 34.5℃. The RR values under high and low temperatures decreased with increasing lag period. When the lag time was extended, the average temperature and RR showed an inverted “U”-shaped relationship, with higher RR at moderate temperatures and increasing as the lag period increased. The results of the subgroups showed that the RR of onset among scattered children was higher at high and low temperatures. Conclusion The risk effect of temperature on the onset of HFMD in different populations is variable and changes with the lag period, and the prevention and control measures should be adjusted in a timely and targeted manner.
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OBJECTIVE To analyze the effects of tigecycline on coagulation function in patients with severe renal insufficiency， and to provide a reference for safe clinical drug use. METHODS Retrospective analysis was performed for the clinical data of patients with severe renal dysfunction complicated with infection receiving tigecycline admitted to nephrology department of our hospital from January 2021 to October 2022. The levels of prothrombin time （PT）， activated partial thromboplastin time （APTT）， international normalized ratio （INR）， platelet （PLT） and fibrinogen （FIB） were compared 3 days before medication， with 1-5， 6-10， 11-15 and 16-20 days after medication， 5 days after withdrawal and/or after symptomatic treatment. RESULTS Finally， 14 patients were included， and 9 patients developed coagulopathy， with an incidence of 64.29%. Compared with 3 days after medication， the levels of FIB at 6-10 and 11-15 days after medication， and PLT at 1-5 ， 6-10 and 11- 15 days after medication were decreased significantly， while the levels of PT at 1-5 and 6-10 days after medication， APTT at 1-5， 6-10 and 11-15 days after medication were significantly prolonged， and INR increased significantly at 1-5 and 6-10 days after medication （P＜0.05）. Compared with 3 days before medication， there were no statistically significant changes in FIB， PT， INR， APTT and PLT at 16-20 days after medication and 5 days after withdrawal and/or symptomatic treatment（P＞0.05）. CONCLUSIONS Patients with severe renal insufficiency should be cautious with tigecycline， which can lead to prolonged PT and APTT， increased INR， and decreased PLT and FIB. If medication time is over 14 days， dynamic monitoring of coagulation function indicators is recommended to reduce the risk of adverse reactions.
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Purpose@#Elevated plasma D-dimer level is a poor prognostic factor for many solid tumors. However, limited research has been conducted on D-dimer in children with neuroblastoma (NB), and its clinical significance remains unclear. The present study investigated the clinical and prognostic significance of D-dimer in pediatric NB patients. @*Methods@#A retrospective analysis of all newly admitted NB patients was conducted from January 2014 to December 2020.Baseline clinicopathological features, preoperative laboratory parameters, and follow-up information were collected. Univariate and multivariate analyses were performed to determine the relationship between D-dimer level, clinical features, and the prognostic value. @*Results@#Among 266 patients, the median value of D-dimer was 2.98 ng/mL, of which 132 patients showed elevated D-dimer levels before surgery (>2.98 ng/mL). Univariate analysis revealed that elevated D-dimer was significantly associated with age, hemoglobin, neutrophil-to-lymphocyte ratio, neuron-specific enolase, 24-hour vanillylmandelic acid, overall survival, and so on (P < 0.05). Patients with elevated D-dimer levels had shorter median overall survival time when compared with normal D-dimer levels (P = 0.01). The prognosis was better in patients with normal D-dimer levels when combined with lower age, ganglioneuroblastoma tumor type, lower stage on International Neuroblastoma Staging System, low-risk group, and without bone metastasis or bone marrow metastasis. The continuous increase of D-dimer level after treatment indicated tumor recurrence or progression. @*Conclusion@#A high D-dimer level is associated with low overall survival, and an elevated D-dimer level after treatment indicates tumor recurrence and progression. D-dimer can be used as one of the evaluation factors for NB treatment or prognosis.
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OBJECTIVE@#To explore the regulatory mechanism of human hepatocyte apoptosis induced by lysosomal membrane protein Sidt2 knockout.@*METHODS@#The Sidt2 knockout (Sidt2-/-) cell model was constructed in human hepatocyte HL7702 cells using Crispr-Cas9 technology.The protein levels of Sidt2 and key autophagy proteins LC3-II/I and P62 in the cell model were detected using Western blotting, and the formation of autophagosomes was observed with MDC staining.EdU incorporation assay and flow cytometry were performed to observe the effect of Sidt2 knockout on cell proliferation and apoptosis.The effect of chloroquine at the saturating concentration on autophagic flux, proliferation and apoptosis of Sidt2 knockout cells were observed.@*RESULTS@#Sidt2-/- HL7702 cells were successfully constructed.Sidt2 knockout significantly inhibited the proliferation and increased apoptosis of the cells, causing also increased protein expressions of LC3-II/I and P62(P < 0.05) and increased number of autophagosomes.Autophagy of the cells reached a saturated state following treatment with 50 μmol/L chloroquine, and at this concentration, chloroquine significantly increased the expressions of LC3B and P62 in Sidt2-/- HL7702 cells.@*CONCLUSION@#Sidt2 gene knockout causes dysregulation of the autophagy pathway and induces apoptosis of HL7702 cells, and the latter effect is not mediated by inhibiting the autophagy-lysosomal pathway.
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Humanos , Proteínas de Membrana Lisossomal/metabolismo , Autofagia , Apoptose , Hepatócitos , Lisossomos/metabolismo , Cloroquina/farmacologia , Proteínas de Transporte de Nucleotídeos/metabolismoRESUMO
ObjectiveTo investigate the effect of microemulsion on the distribution of index components in different phases of Zexietang extract based on high performance liquid chromatography（HPLC） and phase separation process. MethodParticle size meter and transmission electron microscope were used to characterize the colloidal particles in blank microemulsion， aqueous extract of Zexietang and microemulsion extract of Zexietang. The phase separation process was established by high-speed centrifugation and dialysis， and based on this process， the aqueous extract and microemulsion extract of Zexietang were separated into the true solution phase， the colloidal phase and the precipitation phase， respectively. The contents of six components， including atractylenolide Ⅲ， atractylenolide Ⅱ， 23-acetyl alisol C， alisol A， alisol B and alisol B 23-acetate， were determined by HPLC with the mobile phase of water（A）-acetonitrile（B） for gradient elution（0-5 min， 40%-43%B； 5-20 min， 43%-45%B； 20-45 min. 45%-60%B； 45-75 min， 60%-80%B）. The solubility of the index components in water and microemulsion was determined by saturation solubility method. ResultThe colloidal particles in the aqueous extract， microemulsion extract and blank microemulsion were all spherical， and the particle size， polydispersity index（PDI） and Zeta potential of the colloidal particles were in the order of aqueous extract >microemulsion extract >blank microemulsion. The results of phase separation showed that the colloidal phase and the true solution phase could be completely separated by dialysis for 2.5 h， and the phase separation process was tested to be stable and feasible. Compared with the aqueous extract of Zexietang， the use of microemulsion as an extraction solvent could increase the contents of atractylenolide Ⅲ， 23-acetyl alisol C， atractylenolide Ⅱ ， alisol A， alisol B and alisol B 23-acetate by 3.75， 6.82， 35.47， 10.66， 35.41， 27.75-fold， and could increase the extraction efficiencies of the latter five constituents by 2.03， 1.15， 1.70， 6.43， 5.53 times. The solubility test showed that the microemulsion could significantly improve the solubility of atractylenolide Ⅱ， alisol A， alisol B and alisol B 23-acetate， but it had less effect on the solubility of atractylenolide Ⅲ and 23-acetyl alisol C. ConclusionMicroemulsion can improve the extraction efficiency and increase the distribution of the index components in the colloidal phase state of Zexietang to different degrees， providing a reference for the feasibility of microemulsion as an extraction solvent for traditional Chinese medicine.
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【Objective】 To establish an enzyme-linked immunosorbent assay (ELISA) method for the determination of residual human coagulation factor Ⅺ in human prothrombin complex and validate the method. 【Methods】 Human factor Ⅺ was reacted with the capture antibody coated on the microtiter plate. After appropriate washing steps, biotinylated primary antibody was bound to the captured protein. Excess primary antibody was washed away and bound antibody was reacted with horseradish peroxidase conjugated streptavidin. TMB substrate was used for color development at 450 nm. The dilution reliability, accuracy, specificity, repeatability, intermediate precision, linearity, range and durability were verified. 【Results】 The verification results showed that the accuracy and specificity of this method met the experimental requirements, with an average recovery rate of 109.2% and RSD of 6.93%. The repeatability RSD was 6.78%, and the intermediate precision RSD was 6.75%, indicating good precision. The linear regression correlation coefficient of standard curve was 0.999 9, showing good accuracy and precision within the linear range. The durability was verified by the incubation time and the validity period of reagent kit opening. The results showed that the RSD of the incubation time change was 6.62%, indicating that the incubation time of this detection method was controlled between 28 to 32 minutes, and there was no significant impact on the results. The RSD of the detection results before and after the reagent kit was opened and stored under conditions for 7 days was 3.84%, indicating that the preservation of the reagent kit according to the conditions for 7 days after opening has no effect on the FⅪ detection results. Both indicated that the method had good durability. The dilution reliability results showed that there was a "hook" effect in the detection of FⅪ residue in human prothrombin complex, which could be solved by diluting 100 to 200 times. 【Conclusion】 This method can be used for the determination of FⅪ residues of human prothrombin complex in laboratory.
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【Objective:】 To explore the network characteristics of sleep quality and anxiety in first-line medical staff fighting against COVID-19, further understand the relationship between sleep quality and anxiety, and provide basis for intervention. 【Methods:】 Using the convenient sampling method, this paper used the Pittsburgh Sleep Quality Index (PSQI) and Self Rating Anxiety Scale (SAS) to conduct a questionnaire survey on the front-line medical staff who fought against the epidemic during the COVID-19. Network analysis was used to construct sleep quality and anxiety network, and R language was used for statistical analysis and visualization. 【Results:】 In the network of sleep quality and anxiety of first-line medical staff fighting against COVID-19, "sleep disorder" and "sleep quality", "unfortunate premonition" and "inability to sit still", "syncope" and "hand and foot tingling" were highly related. "Fatigue", "dizziness" and "panic" had the highest expected influence. "Sleep quality", "sleep disorder" and "fatigue" had the highest bridge expected influence. The average predictability value of all nodes was 0.778. 【Conclusion:】 This paper used network analysis to explore the sleep quality and anxiety of first-line medical staff fighting against COVID-19 and found that there was a unique correlation path between them. Intervention against core symptoms can ameliorate anxiety and sleep problems to the great extent, and provide guidance for improving the physical and mental health.
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【Objective:】 To explore the network structure characteristics and core items of meaning in life and coping styles among college students, and provide a basis for understanding their relationships and related interventions. 【Methods:】 A survey was conducted among college students using the Simplified Coping Style Questionnaire and Meaning in Life Questionnaire . The network analysis method was used to construct a network of college students’ meaning in life and coping styles, and R software was used for statistical analysis and visualization. 【Results:】 In the network of college students’ meaning in life and coping styles, "believing that time will change the status quo, and the only thing to do is to wait" and "trying to forget the whole thing" had the closest connection. "Learning from others to handle similar difficult situations" had the highest expected impact. "Seeking the meaning in life" and "pursuing hobbies and actively participating in cultural and sports activities" had the highest bridge expected influence. The average predictability value of all nodes was 0.775. 【Conclusions:】 Interventions aimed at "learning from others to handle similar difficult situations", "changing one’s own ideas and rediscovering what is important in life" and "changing some of the original practices or problems" may maximize the coping effect of college students. "Seeking the meaning in life" can furthest influence the coping styles, and "pursuing hobbies and actively participating in cultural and sports activities" can maximize the improvement of meaning in life.