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1.
Article in Chinese | WPRIM | ID: wpr-905158

ABSTRACT

Objective:To investigate the depression status of caregivers of children with disabilities and analyze the influencing factors. Methods:From August to September, 2020, a one-to-one interview was conducted using a convenience sampling method to determine the depression status of 334 caregivers of children with disabilities in Shanghai. Patient Health Questionnaire 9 Item (PHQ-9) was used to evaluate the depression status. The data were analyzed with univariate analysis from three aspects: caregiver, care recipient and environment. Then, the statistically significant variables were included in a dichotomous logistic regression. Results:The depression rate of 334 caregivers of children with disabilities was 35.9%. Among the caregiver factors, female caregivers had a higher risk of depression than male (OR = 2.193, 95%CI 1.131 to 4.254, P = 0.002). Among the care recipient factors, poor sleep quality (OR = 1.942, 5%CI 1.113 to 3.386, P < 0.05), emotional instability (OR = 17.456, 95%CI 2.534 to 120.240, P < 0.05) and types of disability (ORintelligence = 5.401, 95%CI 1.995 to 14.624; ORmental = 3.712, 95%CI 1.615 to 8.530; ORphysical = 2.913, 95%CI 1.330 to 6.379; P < 0.05) were associated with the depression of caregivers. Among the environmental factors, caregivers in rented housing had a higher risk of depression than those in owner-occupied housing (OR = 1.727, 95%CI 1.135 to 2.627, P < 0.05). Conclusion:The depression status of caregivers of children with disabilities is not optimistic, with higher rates of reported depression among female caregivers, caregivers in rented housing; caregivers of children with intellectual, mental and physical disabilities, and poor sleep quality and emotional instability.

2.
Article in Chinese | WPRIM | ID: wpr-905154

ABSTRACT

Objective:To explore the current status of the quality of life of children with disabilities and its influencing factors. Methods:From December, 2019 to January, 2020, and August to September, 2020, a total of 285 family caregivers of children with disabilities were enrolled in Shanghai. The EuroQol-5 Dimension Questionnaire Youth Version (EQ-5D-Y) was used to measure the quality of life of 285 children with disabilities. The impact of individual factors, caregiver factors, and environmental factors (family factors and social factors) on children's quality of life were analyzed using multiple linear stepwise regression analysis. Results:The score of Visual Analog Scale (VAS) was (71.66±22.33). The quality of life were poorer for children with physical disabilities (B = -13.623, 95%CI -25.282 to -1.965, P = 0.022) or multiple disabilities (B = -14.911, 95%CI -27.445 to -2.377, P = 0.020), combined diseases (B = -8.995, 95%CI -14.780 to -3.210, P = 0.002), emotional instability (B = -4.414, 95%CI -7.433 to -1.395, P = 0.004), poor partnerships (B = 4.965, 95%CI 1.748 to 8.181, P = 0.003), no pre-school education (B = -7.757, 95%CI -12.954 to -2.561, P = 0.004) and grandparents as the main caregiver (B = -7.999, 95%CI -14.288 to -1.710, P = 0.013). Conclusion:The quality of life for children with disabilities is relatively poor and influenced by multiple factors such as children's individual, caregivers, and environment. The main influencing factors are individual factors and caregiver factors.

3.
Journal of Medical Biomechanics ; (6): E102-E109, 2021.
Article in Chinese | WPRIM | ID: wpr-904372

ABSTRACT

Objective To propose a quick and low-cost personalized diabetic foot modeling and insole design scheme, so as to reduce the plantar pressure accurately. Methods The foot model of the patient was constructed by scaling the model with foot feature parameters, to make biomechanical analysis on plantar pressure. By means of numerical mapping model of insole elasticity and plantar pressure, the three-dimensional (3D) personalized insole model with gradient modulus was constructed. The insole was then manufactured via 3D printing technology and used for experimental validation. Results The related mechanical parameters from finite element prediction of the foot model constructed by the scaling modeling method were close to those of the CT reconstructed model, and the maximum error was controlled within 15%. Compared with wearing the normal insole, the peak pressure of the personalized insole was effectively reduced by 20%. The time and economic cost of this simplified design was reduced by approximately 90%. Conclusions The design scheme of the diabetes insole shortens the design cycle, and the personalized insole can effectively and accurately reduce the sole pressure, and reduce the risk of foot ulcer, which provides a technical basis for the promotion of the personalized diabetes insole.

4.
Article in English | WPRIM | ID: wpr-921868

ABSTRACT

The recent spring up of the antineoplastic agents and the prolonged survival bring both challenge and chance to radiological practice. Radiological methods including CT, MRI and PET play an increasingly important role in evaluating the efficacy of these antineoplastic drugs. However, different antineoplastic agents potentially induce different radiological signs, making it a challenge for radiological response evaluation, which depends mainly on one-sided morphological response evaluation criteria in solid tumors (RECIST) in the status quo of clinical practice. This brings opportunities for the development of radiomics, which is promising to serve as a surrogate for response evaluations of anti-tumor treatments. In this article, we introduce the basic concepts of radiomics, review the state-of-art radiomics researches with highlights of radiomics application in predictions of molecular biomarkers, treatment response, and prognosis. We also provide in-depth analyses on major obstacles and future direction of this new technique in clinical investigations on new antineoplastic agents.


Subject(s)
Antineoplastic Agents/therapeutic use , Humans , Magnetic Resonance Imaging , Neoplasms/drug therapy , Prognosis
5.
China Pharmacy ; (12): 2059-2065, 2021.
Article in Chinese | WPRIM | ID: wpr-886739

ABSTRACT

OBJECTIVE:To i nvestigate the metabolism stabilities of novel hypoglycemic compound LSM- 13 in rat liver microsomes,and to analyze the possible metabolites. METHODS :LSM-13 was dissolved in rat liver microsome incubation system initiated by reduced nicotinamide adenine dinucleotide phosphate ,and was incubated in water at 37 ℃. The reaction was terminated with acetonitrile at 0,5,10,15,30,45 and 60 min,respectively. Using indomethacin as internal standard ,the concentration of LSM-13 in incubation system was determined by HPLC. The residual percentage and enzyme kinetic parameters of LSM- 13 were calculated at different incubation time points with the concentration of LSM- 13 incubated for 0 min as reference. UPLC-Q-TOF/MS was used to analyze and speculate the metabolites of LSM- 13 in rat liver microsomes. RESULTS :After 60 min incubation ,the remaining percentage of LSM- 13 was(56.07±0.95)%,the half-life was 42.78 min,and the intrinsic clearance was 0.032 4 mL/(min·mg). Compared with total ion flow diagram of rat liver microsome blank samples ,three chromatographic peaks were added in the samples incubated for 60 min;the corresponding molecular ion peaks were m/z 505.133 8,417.102 4,293.111 7 [M+H]+;the possible metabolites may be dehydrogenation ,O-debentylation and hydrolysis products of LSM- 13. CONCLUSIONS : The compound LSM- 13 has moderate stability in rat liver microsomes ,and may undergo dehydrogenation ,O-debentylation and hydrolysis.

6.
Article in Chinese | WPRIM | ID: wpr-886509

ABSTRACT

@#Objective    To summarize the clinical experience of surgical resection of synchronous multiple ground-glass nodules (SMGN), and explore the individualized diagnosis and treatment strategy of SMGN. Methods    Clinical data of 84 patients with SMGN who underwent thoracic surgery in Anhui Chest Hospital from July 2016 to August 2018 were analyzed retrospectively, including 18 males (21.4%) and 66 females (78.6%), aged 32-80 (55.6±10.3) years. The results of operation and the information of GGNs were analyzed. Results    Except for 1 patient who was converted to thoracotomy due to extensive dense adhesion of thoracic, other patients underwent video-assisted thoracoscopic surgery successfully. All patients recuperated successfully after operation, without severe perioperative complications or death. Finally, 79 patients were diagnosed as malignant tumors (94.0%), and 5 patients of benign lesions (6.0%). A total of 240 GGNs were removed, among which there were 168 pGGNs, including 68 benign lesions (40.5%) and 100 malignant tumors (59.5%), and 72 mGGNs, including 2 benign nodules (2.8%) and 70 malignant tumors (97.2%). Nodules diameter (P<0.001), consolidation/maximum diameter of nodule ratio (P<0.001), vacuole sign (P<0.001), air bronchograms sign (P=0.001), spine-like process (P=0.001), pleural indentation sign (P<0.001), lobulation sign (P<0.001), and vascular convergence (P=0.002) were correlated with malignant tumor. Conclusion    Analysis of the imaging features of GGNs by thin-section CT scan and three-dimensional reconstruction is of great value in predicting the benign and malignant nodules, which can guide the surgical decision-making and preoperative planning. Through reasonable preoperative planning and following certain principles, simultaneous surgical treatment for SMGN is safe and feasible.

7.
China Pharmacy ; (12): 1728-1733, 2021.
Article in Chinese | WPRIM | ID: wpr-882144

ABSTRACT

OBJECTIVE:To establish the method for determining protein binding rate of dipeptidyl peptidase- 4 inhibitor LGT- 6 in different species of plasma ,and to compare their difference. METHODS :By equilibrium dialysis ,LGT-6(3,30,300,3 000 nmol/L)was equilibrated in rat ,monkey and human plasma (i. e. internal dialysis solution )for 48 h,using phosphate buffer as the external dialysis solution. The concentration of LGT- 6 in internal and external dialysis solution was determined by UPLC-MS/MS using tolbutamide as internal standard ,and the plasma protein binding rate was calculated. The determination was performed on ACQUITY UPLC HSS T 3 column with water (containing 0.01% formic acid )-acetonitrile(containing 0.01% formic acid )as mobile phase at the flow rate of 0.6 mL/min. The column temperature was 40 ℃,and the sample size was 2 μL. The ion source was electrospray ion source ,and the multiple ion monitoring mode was used to carry out positive ionization scanning. The ion pairs for quantitative analysis were m/z 487.0→434.3(LGT-6),m/z 271.1→172.0(internal standard ),respectively. RESULTS :At the concentrations of 3,30,300,and 3 000 nmol/L,the protein binding rates of LGT- 6 in rat plasma were (96.25±0.97)%,(84.16± 1.24)%,(78.25±0.61)%,(66.63±0.95)%;the protein protein binding rates in monkey plasma were (98.54±0.58)%,(87.27± 1.01)%,(79.35±0.86)%,(66.69±0.54)%;the protein binding rates in human plasma were (99.40±1.03)%,(84.48± 1.15)%,(77.62±0.77)%,(66.93±0.48)%. At the same concentration ,the protein binding rates of LGT- 6 in rat ,monkey and human plasma had no significant difference (P>0.05). In the same species of plasma ,there were significant differences in the plasma protein binding rates of different concentration of LGT-6 among those groups (P<0.05),and it decreased with 才〔2016〕4015) the increase of drug concentration. CONCLUSIONS : The method for the determination of plasma protein binding rate of LGT-6 is successfully established. The data revealed that the protein binding rate of LGT- 6 is concentration-dependent , there was no obvious spec ies difference on protein binding rates of LGT- 6 in rat ,monkey and human plasma under the same concentration.

8.
Article in English | WPRIM | ID: wpr-881064

ABSTRACT

Enterovirus 71 (EV71) infection is more likely to cause hand, foot and mouth disease (HFMD) in children, which can lead to neurogenic complications and higher mortality. As a commonly used clinical medicine, Reduning injection (RDN) helps to shorten the symptoms of patients with HFMD and facilitate the early recovery of children. However, the regulatory mechanism of RDN on the HFMD immune system disorder caused by EV71 remains to be discussed. This study collected detailed treatment data of 56 children with HFMD who entered the affiliated Children's Hospital of Nanjing Medical University during 2019. Retrospective analysis of clinical data showed that the symptoms of the RDN treatment group were improved compared with the untreated group. To explore its mechanism, the relevant detection indicators were detected by flow cytometry, enzyme-linked immunosorbent assay and real-time quantitative PCR. It was found that the number and function of innate immune (ILCs) and adaptive immunity (Th1, Th2 and secreted cytokines) were reduced, suggesting that RDN plays a role by regulating cellular immunity. The in vitro differentiation inhibition test further confirmed that RDN affected Th1 differentiation by inhibiting the expression of transcription factors on the basis of Th1 cell differentiation in vitro.

9.
Article in English | WPRIM | ID: wpr-878316

ABSTRACT

Objective@#The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population.@*Methods@#The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models.@*Results@#A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices).@*Conclusion@#An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.


Subject(s)
Aged , Asians , Blood Glucose/analysis , China/epidemiology , Cohort Studies , Diabetes Mellitus/blood , Female , Glucose Tolerance Test , Glycated Hemoglobin A/analysis , Glycemic Index , Humans , Male , Middle Aged , Uric Acid/blood
10.
China Pharmacy ; (12): 1325-1329, 2021.
Article in Chinese | WPRIM | ID: wpr-877253

ABSTRACT

OBJECTIVE:To establish the metho d for the concentration det ermination of foretinib derivative LWK- 126 in liver microsomes,and to study its metabolism stability in liver microsomes of rats ,Beagle dogs and human. METHODS :In the in vitro incubation system of liver microsomes ,LWK-126 was dissolved in liver microsomal incubation systems of rats ,Beagle dog and human initiated by reduced nicotinamide adenine dinucleotide phosphate solution. After incubation in water at 37 ℃ for 0,5,10,20, 30 and 60 min,the reaction was terminated with acetonitrile containing internal standard (1 μg/mL tolbutamide). UPLC-MS/MS method was applied to determine the concentration of LWK- 126 in the incubation systems. The determination was performed on Waters BEH C 18 column with mobile phase consisted of water (containing 0.1% formic acid )-acetonitrile(containing 0.1% formic acid)by gradient elution at the flow rate of 0.4 mL/min. The column temperature was 30 ℃,and the sample size was 2 μL. The mass spectral analysis was performed in a positive electrospray ionization mode ,and the full MS experiment was run with the selective reaction monitoring mode with a scanning range of m/z 50→1 200. Taking the concentration of LWK- 126 at 0 min as reference,the remaining percentage and the enzyme kinetic parameters were calculated. RESULTS :The linear range of LWK- 126 was 0.05-15 μg/mL(R 2=0.999 2);the lower limit of quantification was 0.05 μg/mL,and the lowest detection limit was 0.01 μg/mL. The precision,accuracy,extraction recovery and matrix effect all met the analysis requirements of biological samples. The remaining percentage of LWK- 126 in liver microsomes of human ,rats and Beagle dogs for 60 min were (33.17±4.52)%,(3.14± 6.73)%,(1.38±5.85)%;t1/2 of them were 33.15,11.76,5.62 min;the clearance rates were 38.45,118.81,245.76 μL(/ min·mg), respectively. CONCLUSIONS :The method for the content ; determination of LWK- 126 in liver microsomes is established successfully. The order of metabolic stability of LWK- 126 in 〔2016〕4015) liver microsomes of different species is human >rats>Beagle dogs.

11.
China Pharmacy ; (12): 195-200, 2021.
Article in Chinese | WPRIM | ID: wpr-862643

ABSTRACT

OBJECTIVE:To study the inhibitor y effects of cajanonic acid A on 5 kinds of cytochrome P 450(CYP)enzyme,in human liver microsomes in vitro . METHODS :By Cocktail probe substrate method ,50.0,15.0,5.0,1.5,0.5,0.15,0.05 μmol/L cajanonic acid A were added into liver microsomes , and incubated with mixed probe substrates [including phenacetin , dextromethorphan,omeprazole,testosterone and toluenesulfonbutylurea (probe substrates of CYP 1A2,CYP2D6,CYP2C19, CYP3A4,CYP2C9,respectively)]. On the basis of setting up blank group and positive control group [ α-naphthalene brass , quinidine,(+)-N-3-benzyl vanillin ,ketoconazole and sulfabendazole (specific inhibitors of CYP 1A2,CYP2D6,CYP2C19, CYP3A4,CYP2C9,respectively)],using puerarin as internal standard ,UPLC-MS/MS method was adopted to determine the contents of corresponding metabolites (acetaminophen, dextrophane, 5-hydroxy omeprazole , 6 β-hydroxytestosterone, hydroxytolbutamide). The determination was performed on ACQUITY UPLC ® BEH C 18 column,with mobile phase consisted of 0.01% formic acid aqueous solution- 0.01% acetonitrile formic acid (gradient elution )at the flow rate of 0.4 mL/min. The column temperature was 40 ℃,and the sample size was 2 μL. An electrospray ionization source was used to conduct positive and negative ion scanning in the multiple reaction monitoring mode. The data acquisition range was m/z 100-1 200,the collision gas was argon , the atomized gas was nitrogen ,the gas flow rate of the cone hole was 50 L/h,the desorption gas flow rate was 800 L/h,the capillary voltage under positive and negative mode was 2.0, 1.5 kV,and the ion source temperature was 120 ℃,110 ℃, respectively. The desolvent temperature were 400 ℃ and 450 ℃ , respectively. Non linear regression analysis was performed by using Graphpad Prism 5.0 software and IC 50 wascalculated. RESULTS :The linear ranges of above metabolifes were 0.26-8.35,0.36-34.56,0.10-3.09, 3.67-117.37,0.15-4.88 μmol/L(R2>0.99). The limits of quantitation were 0.26,0.36, 0.10,3.67,0.15 μmol/L,respectively. The IC 50 values of specific inhibitors in positive control group to CYP 1A2,CYP2D6, CYP2C19,CYP3A4 and CYP 2C9 in human liver microsomes were all within the acceptable range reported in the literature. The IC50 values of cajanonic acid A to CYP 1A2,CYP2D6 and CYP 3A4 in human liver microsomes were all more than 50 μmol/L,and the IC 50 values of CYP 2C9 and CYP 2C19 were 4.94 and 18.00 μmol/L,respectively. CONCLUSIONS :Cajanonic acid A has no inhibitory effect on CYP 1A2,CYP2D6 and CYP 3A4,but has a certain inhibitory effect on CYP 2C9 and CYP 2C19.

12.
Article in Chinese | WPRIM | ID: wpr-856314

ABSTRACT

Objective: To investigate the early effectiveness of proximal femur reconstruction combined with total hip arthroplasty (THA) in the treatment of adult Crowe type Ⅳ developmental dysplasia of the hip (DDH). Methods: Between May 2015 and March 2018, 29 cases (33 hips) suffering from Crowe type Ⅳ DDH were treated with proximal femur reconstruction combined with THA. Of the 29 cases, there were 6 males (7 hips) and 23 females (26 hips), aged from 24 to 74 years with an average age of 44.9 years. The preoperative Harris hip score was 44.0±12.0. Gait abnormalities were found in all of the 33 hips with positive Trendelenburg sign, and the lower limb discrepancy was (3.8±1.6) cm. Preoperative X-ray films and CT both indicated serious anatomical abnormalities, including complete dislocation of the affected hip with significant move-up of the greater trochanter, abnormal development of the femoral neck, abnormal anterversion angle and neck-shaft angle, dysplasia of proximal femur and dysplasia of medullary cavity. The operation time, intraoperative blood loss, transfusion rate, and complications were recorded. The Gruen and DeLee-Charnley zoning methods were used to evaluate the aseptic loosening of the prosthesis on X-ray films. The Harris score was used to evaluate hip function. The lower limb discrepancy was calculated and compared with the preoperative value. Results: The operation time ranged from 80 to 240 minutes, with an average of 124.8 minutes. The intraoperative blood loss ranged from 165 to 1 300 mL, with an average of 568.4 mL. Seventeen patients (51.5%) received blood transfusion treatment. All the incisions healed by first intention without infection or deep vein thrombosis. All patients were followed up 19-53 months, with an average of 33 months. One patient had posterior hip dislocation because of falling from the bed at 4 weeks after operation, and was treated with manual reduction and fixation with abduction brace for 4 weeks, and no dislocation occurred during next 12-month follow-up. Two patients developed sciatic nerve palsy of the affected limbs after operation and were treated with mecobalamin, and recovered completely at 12 weeks later. Trendelenburg sign was positive in 3 patients and mild claudication occurred in 4 patients after operation. X-ray films showed that all the osteotomy sites healed at 3-6 months after operation, and no wire fracture was observed during the follow-up. The Harris score was 89.8±2.8 and lower limb discrepancy was (0.6±0.4) cm at last follow-up, both improved significantly ( t=-22.917, P=0.000; t=11.958, P=0.000). The prosthesis of femur and acetabulum showed no obvious loosening and displacement, and achieved good bone ingrowth except 2 patients who had local osteolysis in the area of Gruen 1 and 7 around the femoral prosthesis, but no sign of loosening and sinking was observed. Conclusion: The treatment of Crowe Ⅳ DDH with proximal femur reconstruction and THA was satisfactory in the early postoperative period. The reconstruction technique of proximal femur can effectively restore the anatomical structure of proximal femur, which is one of the effective methods to deal with the deformity of proximal femur.

13.
Article in English | WPRIM | ID: wpr-827790

ABSTRACT

This study engineered β-carotene ketolase CrtW and β-carotene hydroxylase CrtZ to improve biosynthesis of astaxanthin in Escherichia coli. Firstly, crtW was randomly mutated to increase CrtW activities on conversion from β-carotene to astaxanthin. A crtW* mutant with A6T, T105A and L239M mutations has improved 5.35-fold astaxanthin production compared with the wild-type control. Secondly, the expression levels of crtW* and crtZ on chromosomal were balanced by simultaneous modulation RBS regions of their genes using RBS library. The strain RBS54 selected from RBS library, directed the pathway exclusively towards the desired product astaxanthin as predominant carotenoid (99%). Lastly, the number of chromosomal copies of the balanced crtW-crtZ cassette from RBS54 was increased using a Cre-loxP based technique, and a strain with 30 copies of the crtW*-crtZ cassette was selected. This final strain DL-A008 had a 9.8-fold increase of astaxanthin production compared with the wild-type control. Fed-batch fermentation showed that DL-A008 produced astaxanthin as predominant carotenoid (99%) with a specific titer of 0.88 g·L without addition of inducer. In conclusion, through constructing crtW mutation, balancing the expression levels between crtW* and crtZ, and increasing the copy number of the balanced crtW*-crtZ cassette, the activities of β-carotene ketolase and β-carotene hydroxylase were improved for conversion of β-carotene to astaxanthin with higher efficiency. The series of conventional and novel metabolic engineering strategies were designed and applied to construct the astaxanthin hetero-producer strain of E. coli, possibly offering a general approach for the construction of stable hetero-producer strains for other natural products.

14.
China Pharmacy ; (12): 1452-1445, 2020.
Article in Chinese | WPRIM | ID: wpr-822364

ABSTRACT

OBJECTIVE:To investigate th e stabilities of antitumor candid ate Gedatolisib in plasma in vitro and simulated gastric/intestinal fluids ,and to analyze the possible catabolites in plasma. METHODS :HPLC method was adopted. Using indometacin as internal standard ,the contents of Gedatolisib incubated in plasma of SD rats (male)for 0,0.5,1.0,1.5,2.0,3.0 h and blank simulated gastric fluid (pH 1.3,no enzyme ),blank simulated intestinal fluid (pH 6.8,no enzyme ),simulated gastric fluid(pH 1.3,containing pepsin )and simulated intestinal fluid (pH 6.8,containing trypsin )for 0,0.5,1.0,2.0,3.0,4.0,6.0 h were determined. The remaining percentage of Gedatolisib was calculated. UPLC-Q-TOF/MS was used to analyze the TIC of blank plasma and incubated samples. The differential peaks were compared, and catabolites were inferred by MS 1Z073).gzwjkj2019-1- chromatograms. RESULTS : The remaining percentage in plasma of rats for 2.0 h was about 63%,and there was nosignificant change after continued incubation. The remaining percentage of Gedatolisib incubated in blank simulated intestinal fluid for different time ranged (99.18 ± 2.15)% -(103.20 ± 3.41)% . The remaining percentage in simulated com intestinal fluids for 2.0 h ranged (88.76 ± 1.53)% . The remaining percentage in blank simulated gastric fluids for 2.0 h was ranged (85.63±1.55)%,and there was no significant change after continued incubation. The remaining percentage in simulated gastric fluid was from (94.94±3.52)%(0 h)to(16.19±1.17)% (6.0 h). TIC of UPLC-Q-TOF/MS showed that the differential peaks of incubated samples and blank plasma was 6.42 min under positive mode scanning ,molecular ion peak of m/z 616.335 1,simulated 632.327 7,630.317 0,602.278 6 [M+H]+ could be found in scanning channel. It was speculated that Gedatolisib could generate 1-(4-(3-(4,6-dimorpholino-1,3,5-triazin-2-yl)phenyl)urea) benzoyl)-N,N-dimethylpiperidin-4-amine oxide ,1-(4-(4-(dimethylamino)piperidine-1-carbonyl)phenyl)-3-(4-(4-morpholino-6- (3-oxomorpholino)-1,3,5-triazin-2-yl)phenyl)urea and 1-(4-(3-(4-(4,6-dimorpholino-1,3,5-triazin-2-yl)phenyl)urea) benzoyl)-N-methylpiperidine. CONCLUSIONS :Gedatolisib is not stable in rat plasma ,and it may undergo terminal N oxidation, morpholine ring oxidation and terminal N demethylation. Gedatolisib is stable in artificial intestinal fluid and blank artificial gastric/ intestinal fluid ,and degrades obviously in the presence of pepsin.

15.
China Pharmacy ; (12): 800-805, 2020.
Article in Chinese | WPRIM | ID: wpr-819090

ABSTRACT

OBJECTIVE:To isolate and purify baicalin metabolites from rat bile ,and to study its effect on the proliferation of liver cancer HepG 2 cells. METHODS :Totally of 6 SD rats were collected ,anesthetized and then intubated with bile ducts. They were given baicalin (168 mg/kg)intragastrically after the rats were awake as well as the bile sample 1 was collected during 24 h after intragastric administration. After processed ,bile sample 1 was preliminarily analyzed by HPLC. Another 5 SD rats were anesthetized and intubated in the same way as above ,and then given baicalin intragastrically (400 mg/kg). The bile sample 2 was collected during 48 h after intragastric administration. After processed ,the bile sample 2 was isolated and purified by semi-preparative HPLC. The isolated metabolites were identified by using UV ,IR,MS and NMR ,as well as based on physical and chemical properties. MTT method combined with high content cell imaging analysis system was used to study the effect of the metabolites on the proliferation of HepG 2 cells. RESULTS :Baicalin was mainly metabolized into metabolite 1 and metabolite 2 through bile. After isolation and purification , they were identified as oroxylin A- 7-O-β-D-glucuronide and 2726719792@qq.com baicalein 6-O-β-D-glucuronide. The results of MTT assay showed that the metabolite 2 had a significant inhibitory effect 分析。E-mail:gaoxl@gmc.edu.cn on the proliferation of HepG 2 cells,and its IC 50 was 90 µg/mL;the results of high content cell imaging analysis showed that at a certain concentration metabolite 2 may inhibit proliferation by changing the mitochondrial distribution and membrane permeability of HepG 2 cells(studies on the pharmacological activities of metabolism 1 had been reported ,it was skipped in this study ). CONCLUSIONS :In this study ,two baicalin bile metabolites were successfully isolated and identified ,of which baicalein 6-O-β-D-glucuronide has a significant inhibitory effect on the proliferation of HepG 2 cells.

16.
Article in Chinese | WPRIM | ID: wpr-817630

ABSTRACT

@#【Objective】To explore the role of lncRNA Xist in proliferation and migration of rat bone marrow mesenchymal stem cells(BMSC)and its possible mechanism.【Methods】BMSC were isolated,cultured and identified from the femur and tibia of 3 weeks old SD female rats in vitro. SiRNAs was designed and screened to acquire a high silencing efficiency siRNA. Lipo2000 was used to transfected si- Xist and si- NC into BMSC of the experimental group(si- Xist group)and the control group(si-NC group). BMSC proliferation capacity was determined by CCK-8 assay. The transverse and longitudinal mobility of BMSC were measured by wound healing assay and transwell migration assays. QPCR was performed to verify the silencing efficiency of lncRNA Xist and detect the expression levels of SDF- 1 and CXCR4 mRNA. Western blot was used to quantify the expression of CXCR4 protein.【Results】The P3 generation BMSC shows shuttle- like or whirlpool-like,and flow cytometry showed CD11b(-),CD34(-),CD45(-),CD44(+),CD90(+),CD105(+). When siRNAs were used to interfere with the expression of lncRNA Xist in BMSC ,the silencing efficiency of three siRNAs was 67.92% ,68.72% and 98.32% ,respectively. CCK- 8 assay showed that the OD450 value of si- Xist group decreased compared with si-NC group at 24 h and 48 h(P < 0.001,P < 0.01,respectively)and had no statistical difference at 12 h(P > 0.05). Wound healing assay showed that the wound healing percentage of si-Xist group was lower than that of si-NC group(P < 0.05);and the transwell migration assay showed that,compared with si- NC group,the cells that migrated through the polycarbonate membrane were obviously decreased at 6 h(P < 0.001). QPCR experiment showed that CXCR4 expression in si-Xist group was lower than that in si-NC group at mRNA level(P < 0.05),while SDF-1 expression showed no significant statistical difference(P > 0.05). Western blotting confirmed that CXCR4 expression in si- Xist group was lower than that in si-NC group(P < 0.05).【Conclusions】LncRNA Xist promotes proliferation and migration of rat BMSC by regulating CXCR4 expression.

17.
Chinese Journal of Urology ; (12): 681-686, 2020.
Article in Chinese | WPRIM | ID: wpr-869727

ABSTRACT

Objective:To establish a predictive model that can predict the effectiveness and safety of endoscopic surgery for pediatric upper urinary tract calculi, and evaluate its diagnostic efficacy through internal validation.Methods:The data was selected from the prospective database of pediatric upper tract calculi constructed by Beijing Friendship Hospital Affiliated to Capital Medical University from June 2014 to April 2019. A total of 348 children were recruited in this investigation including 250 boys and 98 girls, with a median age of 3.0 years(Interquartile Range 1.4, 7.0 years). Totally 375 endoscopic surgeries were performed, with an overall stone free rate (SFR) of 88.0% (330/375) and complication rate (CR) of 23.2% (87/375). This research used univariate and multivariate logistic regression analysis to evaluate and screen the predictors of SFR and CR. The nomogram of SFR and CR was established by using the selected predictive factors. The differentiation degree of the model was evaluated by the area under the curve (AUC), the consistency between the prediction probability and the actual risk was evaluated by the calibration curve, and the clinical benefits of the model application were assessed by the decision curve.Results:The results of multivariate analysis demonstrated that stone burden, operation duration, intraoperative perfusion, stone location and operative options were the postoperative predictors of SFR and CR for children. Besides, BMI was also a predictor of postoperative CR. The AUC of the model (model 1: SFR; model 2: CR) based on the above predictive factors was 0.81 and 0.73, respectively. The predictive probability of the calibration curve showed that the model had a good consistency with the actual value. The decision curve showed that the application of model 1 to predict SFR had significant clinical benefits when the threshold value was greater than 20%, and the application of model 2 to predict the postoperative CR had a significant clinical benefit when the threshold was greater than 10%.Conclusions:Nomogram based on stone burden, operation time, intraoperative perfusion, stone location and operative options was validated internally with preferable predictive power on the effectiveness and safety of pediatric endoscopic surgery. This model can be used to predict the clinical effects of pediatric endoscopic lithotripsy. BMI was also an important factor for the safety of pediatric endoscopic procedures.

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Chinese Journal of Endemiology ; (12): 703-709, 2020.
Article in Chinese | WPRIM | ID: wpr-866204

ABSTRACT

Objective:To investigate the changes of microRNA-153 (miR-153) expression and the mechanism of regulating histone H3 lysine 4 (H3K4) methyltransferase (SET7/9) and histone H3K4 methylation (H3K4me1) in the process of arsenic-induced endoplasmic reticulum stress-related hepatocytes apoptosis.Methods:Human normal hepatocytes (L-02 cells) were cultured in vitro and divided into control, arsenic treatment, arsenic + negative transfection, arsenic + miR-153 up-regulation and arsenic+ miR-153 down-regulation groups according to different treatment methods. Arsenic+ negative transfection, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were transfected with transfection plasmid and transfection reagent according to a certain proportion (3 μg: 8 μl). After 24 h, arsenic treatment, arsenic+ negative transfection, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were all treated with 100 μmol/L sodium arsenite (NaAsO 2) as the final concentration for 24 h. The control group was treated with phosphate buffer solution (PBS) of the same volume as NaAsO 2 for 24 h. The expression of miR-153 was detected by real-time quantitative polymerase chain reaction (RT-qPCR); cell apoptosis and cell cycle were detected by flow cytometry; real-time cell dynamic analyzer (RTCA) was used to detect cell proliferation; Western blotting was used to detect the expression of endoplasmic reticulum marker proteins glucose regulatory protein 78 (GRP78), SET7/9 and H3K4me1. Results:The expression levels of miR-153 in each group were significantly different ( F = 10.73, P < 0.05). Compared with the control group [(41.10 ± 6.08)%], the expression level of miR-153 in arsenic treatment group [(4.35 ± 0.20)%] was significantly decreased ( P < 0.05); compared with the arsenic+ negative transfection group [(10.00 ± 2.40)%], the expression level of miR-153 in arsenic+ miR-153 up-regulation group [(157.70 ± 42.70)%] was significantly increased ( P < 0.05), and that in arsenic+ miR-153 down-regulation group [(4.20 ± 0.28)%] was significantly decreased ( P < 0.05). There were significant differences in the total cell apoptosis rate and G1 phase cell proportion among the five groups ( F = 29.69, 104.32, P < 0.05). Compared with the control group, the total cell apoptosis rates and G1 phase cell proportions in arsenic treatment, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were significantly increased ( P < 0.05); compared with the arsenic+ negative transfection group, the total cell apoptosis rate and G1 phase cell proportion in arsenic+ miR-153 up-regulation group were significantly decreased ( P < 0.05), and those in arsenic+ miR-153 down-regulation group were significantly increased ( P < 0.05). The difference of cell proliferation rate in each group was statistically significant ( F = 799.35, P < 0.05). Compared with the control group, the cell proliferation rates in arsenic treatment, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were significantly decreased ( P < 0.05); compared with the arsenic+ negative transfection group, the cell proliferation rate in arsenic+ miR-153 up-regulation group was significantly increased ( P < 0.05), and that in arsenic+ miR-153 down-regulation group was significantly decreased ( P < 0.05). The protein expression levels of SET7/9, GRP78 and H3K4me1 in each group were significantly different ( F = 78.52, 52.13, 54.32, P < 0.05). Compared with the control group, the protein expression levels of SET7/9, GRP78 and H3K4me1 in arsenic treatment group were significantly increased ( P < 0.05); compared with the arsenic+ negative transfection group, the protein expression levels of SET7/9, GRP78 and H3K4me1 in arsenic+ miR-153 up-regulation group were significantly decreased ( P < 0.05), and those in arsenic + miR-153 down-regulation group were significantly increased ( P < 0.05). Conclusion:miR-153 plays an important role in arsenic-induced endoplasmic reticulum stress-related hepatocytes apoptosis, the expression and regulation are related to the changes of SET7/9 and H3K4me1 levels.

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Article in Chinese | WPRIM | ID: wpr-865094

ABSTRACT

Objective:To investigate the computed tomography (CT) features of adenocarcinoma of esophagogastric junction (AEG) after neoadjuvant chemotherapy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 59 patients with AEG who underwent neoadjuvant chemotherapy in Peking University Cancer Hospital from February 2010 to November 2014 were collected. There were 51 males and 8 females, aged from 46 to 82 years, with a median age of 63 years. All the 59 patients underwent enhanced CT examination before and after neoadjuvant chemotherapy. Observation indicators: (1) pathological examination and neoadjuvant chemotherapy of patients with AEG; (2) results of CT examination in patients with AEG, including ① qualitative indicators of CT and ② quantitative indicators of CT. Measurement data with skewed distribution were represented as M( P25, P75) or M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed by the chi-square test. Results:(1) Pathological examination and neoadjuvant chemotherapy of patients with AEG: of the 59 patients with AEG, high-differentiated adenocarcinoma was observed in 1 patient, moderate-differentiated adenocarcinoma in 40 patients, and low-differentiated adenocarcinoma in 18 patients. Effective response to neoadjuvant chemotherapy was observed in 13 patients, including 6 patients of pathological tumor regression grading (pTRG) 0 and 7 of pTRG 1; poor response was observed in 46 patients, including 12 patients of pTRG 2 and 34 patients of pTRG 3. (2) Results of CT examination in patients with AEG. ① Qualitative indicators of CT: for the 13 patients with effective response to neoadjuvant chemotherapy, 13 had the presence of ulcers, 5 had layered enhancement, 10 had infiltration of adventitia surface, and 2 had positive extramural venous invasion (EMVI) before neoadjuvant chemotherapy; after neoadjuvant chemotherapy, 13 had shallowed or disappeared ulcers, 7 patients had changed enhancement pattern, 3 had infiltration of adventitia surface, and 1 had positive EMVI. For the 46 patients with poor response to neoadjuvant chemotherapy, 28 had the presence of ulcers, 18 had layered enhancement, 37 had infiltration of adventitia surface, and 22 had positive EMVI before neoadjuvant chemotherapy; after neoadjuvant chemotherapy, 23 had shallowed or disappeared ulcers, 7 patients had changed layered enhancement pattern, 33 had infiltration of adventitia surface and 21 had positive EMVI, respectively. There was no significant difference in the layered enhancement or infiltration of adventitia surface before neoadjuvant chemotherapy between patients with different treatment response ( χ2=0.002, 0.000, P>0.05). There were significant differences in the presence of ulcers and positive EMVI before neoadjuvant chemotherapy between patients with different treatment response ( χ2=5.591, 4.421, P<0.05). After neoadjuvant chemotherapy, there were significant differences in the changes of layered enhancement pattern, infiltration of adventitia surface and positive EMVI between patients with different treatment response ( χ2=6.359, 10.090, 4.728, P<0.05); while there was no significant difference in the shallowed or disappeared ulcers between patients with different treatment response ( χ2=1.239, P>0.05). ② Quantitative indicators of CT: for the 13 patients with good response to neoadjuvant chemotherapy, the maximum tumor height, the maximum tumor area, enhanced CT value of the lesion before neoadjuvant chemotherapy were 1.37 cm(0.94 cm, 1.88 cm), 8.9 cm 2 (4.7 cm 2, 9.9 cm 2), 53 HU(47 HU, 63 HU), respectively. After neoadjuvant chemotherapy, the above indicators were 1.17 cm(0.79 cm, 1.29 cm), 4.4 cm 2(2.5 cm 2, 6.1 cm 2), 30 HU(25 HU, 53 HU), respectively. The change rates of the maximum tumor height, the maximum tumor area, and enhanced CT value of the lesion were -23%(-42%, 9%), -51%(-60 %, -21%), -44%(-51%, 19%), respectively. For the 46 patients with poor response to neoadjuvant chemotherapy, the maximum tumor height, the maximum tumor area, enhanced CT value of the lesion were 1.57 cm(1.21 cm, 1.96 cm), 9.4 cm 2(6.6 cm 2, 13.1 cm 2), 60 HU(53 HU, 66 HU) before neoadjuvant chemotherapy, respectively. After neoadjuvant chemotherapy, the above indicators were 1.16 cm(0.94 cm, 1.37 cm), 6.2 cm 2(4.8 cm 2, 8.1 cm 2), 55 HU(47 HU, 65 HU), respectively. The change rates of the maximum tumor height, the maximum tumor area, and enhanced CT value of the lesion were -27%(-38%, -9%), -33%(-47%, -12%), -9%(-22%, 9%), respectively. There was no significant difference in the maximum tumor height, the maximum tumor area, enhanced CT value of the lesion before neoadjuvant chemotherapy between patients with different treatment response ( Z=-1.372, -1.372, -1.331, P>0.05). There was no significant difference in the maximum tumor height after neoadjuvant chemotherapy between patients with different treatment response ( Z=-0.503, P>0.05), while there were significant differences in the maximum tumor area and CT value of the lesion ( Z=-2.743, -3.049, P<0.05). There was no significant difference in the change rate of the maximum tumor height or the maximum tumor area between patients with different treatment response ( Z=0.000, -1.481, P>0.05), while there was a significant difference in the change rate of CT value of the lesion ( Z=-3.231, P<0.05). Conclusion:Effective response of AEG to neoadjuvant chemotherapy was characterized by the changes in tumor layered enhancement pattern, reduction in the maximum tumor area, reduced CT value of the lesion, negative infiltration of adventitia surface, and negative EMVI.

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Article in Chinese | WPRIM | ID: wpr-864681

ABSTRACT

Objective:To explore and describe the experiences of young breast cancer survivors in transitional period, and to provide basis for the development of targeted rehabilitation nursing measures.Methods:This study was guided by phenomenological theory of qualitative research. 14 cases were deeply interviewed using a semi-structured questionnaire. The information of interview was analyzed, sorted, coded in according to Colaizzi′s analysis, and different themes were extracted.Results:6 themes of the experience of young breast cancer survivors in the transitional period were extracted including: trying to return to normal life, persistent side effects of treatment, problems of partnership and fertility, strong sense of insecurity and uncertainty, career planning and unmet needs.Conclusions:Young breast cancer survivors still face pressure from physiological, psychological and social aspects in the transitional period. Nurses can promote their smooth transition and early recovery by strengthening discharge assessment and planning, providing continuous care, paying attention to long-term symptom management, improving their self-care ability, encouraging their spouses to participate in support and other strategies.

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