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1.
Article in Chinese | WPRIM | ID: wpr-928353

ABSTRACT

OBJECTIVE@#To identify the pathogenic variant for a husband with osteogenesis imperfecta and provide preimplantation genetic testing (PGT) for the couple.@*METHODS@#High-throughput sequencing and Sanger sequencing were carried out to identify the pathologic variant in the husband patients. PGT of embryos was performed through direct detection of the mutation site. Meanwhile, chromosome aneuploidy of the blastocysts was screened. Following transplantation, cytogenetic and genetic testing of fetal amniotic fluid sample was carried out during mid-pregnancy. Chromosome copy number variant (CNV) was detected at multiple sites of the placenta after delivery.@*RESULTS@#The husband was found to harbor heterozygous c.544-2A>G variant of the COL1A1 gene. The same variant was not detected in either of his parents. PGT revealed that out of three embryos of the couple, one was wild-type for the c.544-2A site but mosaicism for duplication of 16p13.3.11.2. The other two embryos were both heterozygous for the c.544-2A>G variant. Following adequate genetic counseling, the wild-type embryo was transplanted. Amniotic fluid testing confirmed that the fetus had normal chromosomes and did not carry the c.544-2A>G variant. The copy number of chromosomes at different parts of placenta was normal after birth.@*CONCLUSION@#For couples affected with monogenic disorders, e.g., osteogenesis imperfecta, direct detection of the mutation site may be used for PGT after identifying the pathogenic variant. After adequate genetic counseling, prenatal diagnosis must be carried out to ensure the result.


Subject(s)
Aneuploidy , China , Female , Genetic Testing , Humans , Osteogenesis Imperfecta/genetics , Pregnancy , Preimplantation Diagnosis
2.
Article in Chinese | WPRIM | ID: wpr-928149

ABSTRACT

The methods for determining the characteristic chromatogram and index components content of Xuanfu Daizhe Decoction were established to provide a scientific basis for the quality evaluation of substance benchmarks and preparations. Eighteen batches of Xuanfu Daizhe Decoction were prepared with the decoction pieces of different batches and of the same batch were prepared respectively, and the HPLC characteristic chromatograms of these samples were established. The similarities of the chromatographic fingerprints were analyzed. With liquiritin, glycyrrhizic acid, 6-gingerol, ginsenoside Rg_1, and ginsenoside Re as index components, the high performance liquid chromatography was established for content determination with no more than 70%-130% of the mass average as the limit. The results showed that there were 19 characteristic peaks corresponding to the characteristic chromatograms of 18 batches of Xuanfu Daizhe Decoction, including 8 peaks representing liquiritin, 1,5-O-dicaffeoylqunic acid, ginsenoside Rg_1, ginsenoside Re, 1-O-acetyl britannilactone, ginsenoside Rb_1, glycyrrhizic acid, and 6-gingerol, and the fingerprint similarity was greater than 0.97. The contents of liquiritin, glycyrrhizic acid, 6-gingerol, and ginsenosides Rg_1 + Re in the prepared Xuanfu Daizhe Decoction samples were 0.53%-0.86%, 0.61%-1.2%, 0.023%-0.068%, and 0.33%-0.66%, respectively. Except for several batches, most batches of Xuanfu Daizhe Decoction showed stable contents of index components, with no discrete values. The characteristic chromatograms and index components content characterized the information of Inulae Flos, Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, and Zingiberis Rhizoma Recens in Xuanfu Daizhe Decoction. This study provides a scientific basis for the further research on the key chemical properties of substance benchmark and preparations of Xuanfu Daizhe Decoction.


Subject(s)
Benchmarking , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/chemistry , Ginsenosides/analysis , Glycyrrhizic Acid/analysis , Quality Control
3.
Article in English | WPRIM | ID: wpr-927631

ABSTRACT

OBJECTIVE@#This study aimed to assess the associations between maternal drug use, cytochrome P450 ( CYP450) genetic polymorphisms, and their interactions with the risk of congenital heart defects (CHDs) in offspring.@*METHODS@#A case-control study involving 569 mothers of CHD cases and 652 controls was conducted from November 2017 to January 2020.@*RESULTS@#After adjusting for potential confounding factors, the results show that mothers who used ovulatory drugs (adjusted odds ratio [a OR] = 2.12; 95% confidence interval [ CI]: 1.08-4.16), antidepressants (a OR = 2.56; 95% CI: 1.36-4.82), antiabortifacients (a OR = 1.55; 95% CI: 1.00-2.40), or traditional Chinese drugs (a OR = 1.97; 95% CI: 1.26-3.09) during pregnancy were at a significantly higher risk of CHDs in offspring. Maternal CYP450 genetic polymorphisms at rs1065852 (A/T vs. A/A: OR = 1.53, 95% CI: 1.10-2.14; T/T vs. A/A: OR = 1.57, 95% CI: 1.07-2.31) and rs16947 (G/G vs. C/C: OR = 3.41, 95% CI: 1.82-6.39) were also significantly associated with the risk of CHDs in offspring. Additionally, significant interactions were observed between the CYP450genetic variants and drug use on the development of CHDs.@*CONCLUSIONS@#In those of Chinese descent, ovulatory drugs, antidepressants, antiabortifacients, and traditional Chinese medicines may be associated with the risk of CHDs in offspring. Maternal CYP450 genes may regulate the effects of maternal drug exposure on fetal heart development.


Subject(s)
Adult , Cytochrome P-450 Enzyme System/genetics , Female , Genotype , Heart Defects, Congenital/genetics , Humans , Infant, Newborn , Polymorphism, Genetic , Pregnancy , Pregnancy Complications/drug therapy
4.
International Eye Science ; (12): 457-461, 2022.
Article in Chinese | WPRIM | ID: wpr-920429

ABSTRACT

@#AIM: To study the incidence and risk factors of posterior capsular opacification(PCO)after cataract surgery in diabetic patients.<p>METHODS: Clinical data of 182 cases(203 eyes)who underwent cataract phacoemulsification combined with intracellular lens implantation in our hospital from April 2016 to August were collected. The patients were divided into diabetic group(DM group, 98 eyes)and non-diabetic group(non-DM group, 105 eyes)according to whether they had diabetes before operation. DM group were divided into groups according to whether PCO occurred 30mo after cataract surgery, 26 eyes in the PCO group, and 72 eyes in non-PCO group. The incidence and grading of PCO in the DM group and the non-DM group were compared. The effects of preoperative diabetic course, HbA1c level and the presence of diabetic retinopathy on PCO in DM group were tested.<p>RESULTS: The incidence of PCO was 10.2%, 14.3%, 22.4%, 26.5% at 12, 18, 24 and 30mo in the DM group and 2.8%, 4.8%, 10.5%, and 14.3% in the non-DM group. Two groups of patients with the degree of PCO are gradually increasing, and the degree of each point in time the PCO patients with DM group were heavier than patients without DM group(all P<0.05). There were differences in the preoperative course of diabetes and the presence of DR between PCO and non-PCO groups(P<0.05), but there was no difference in the preoperative level of HbA1c(P>0.05).<p>CONCLUSION: The incidence of PCO in diabetic patients after cataract surgery was higher than that in non-diabetic patients, and the degree of opacity was more severe. Preoperative course of diabetes and the presence of DR were risk factors for PCO.

5.
Article in Chinese | WPRIM | ID: wpr-879892

ABSTRACT

OBJECTIVE@#To study the association between maternal reduced folate carrier (@*METHODS@#A hospital-based case-control study was conducted. The mothers of 683 infants with CHD who attended the Department of Cardiothoracic Surgery, Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group. The mothers of 740 healthy infants without any deformity who attended the hospital during the same period of time were enrolled as the control group. A questionnaire survey was performed to collect the exposure data of subjects. Venous blood samples of 5 mL were collected from the mothers for genetic polymorphism detection. A multivariate logistic regression analysis was used to evaluate the association of @*RESULTS@#After control for confounding factors, the multivariate logistic regression analysis showed that maternal @*CONCLUSIONS@#Maternal


Subject(s)
Case-Control Studies , Child , Female , Genetic Predisposition to Disease , Genotype , Heart Defects, Congenital/genetics , Humans , Infant , Polymorphism, Single Nucleotide , Reduced Folate Carrier Protein/genetics , Risk Factors
6.
Article in Chinese | WPRIM | ID: wpr-879581

ABSTRACT

OBJECTIVE@#To apply nanopore third-generation sequencing for the detection of chromosomal aneuploidy samples, and explore its performance and application prospects.@*METHODS@#DNA extracted from two human cell lines with X chromosome monosomy and 22.5 Mb deletion in 7q11.23-q21.3 region was sequenced with a MinION sequencer, and the results were analyzed.@*RESULTS@#Respectively, 555 872 and 2 679 882 reads were obtained from the two samples within 24 hours, with genome coverage being 53.75% and 88.63%. With a sequencing depth of 0.81× and 2.40× , respectively, the abnormal chromosomal regions could be detected by comparative analysis using Minimap2.@*CONCLUSION@#With low-depth whole genome sequencing, the use of nanopore third-generation sequencing is expected to complete the detection and analysis of chromosomal aneuploidy samples within 24 hours, but its further application and promotion needs to overcome the cost constraints.


Subject(s)
Aneuploidy , Chromosomes , High-Throughput Nucleotide Sequencing , Humans , Sequence Analysis, DNA , Technology
7.
Article in Chinese | WPRIM | ID: wpr-879525

ABSTRACT

OBJECTIVE@#To carry out genetic testing for an abortus suspected with Cornelia de Lange syndrome (CdLS).@*METHODS@#History of gestation and the family was taken. Combined with prenatal ultrasonography and the phenotype of the abortus, a diagnosis was made for the proband. Fetal tissue and peripheral blood samples of its parents were collected for the extraction of genomic DNA. Whole exome sequencing was carried out to detect mutations related to the phenotype. Suspected mutations were verified in the parents through Sanger sequencing.@*RESULTS@#Prenatal ultrasound found that the forearms and hands of the fetus were anomalous, in addition with poorly formed vermis cerebellum, slight micrognathia, and increased echo of bilateral renal parenchyma. Examination of the abortus has noted upper limb and facial malformations. Whole exome sequencing revealed that the fetus carried a heterozygous c.2118delG (p.Lys706fs) frameshift mutation of the NIPBL gene. The same mutation was not found in either parent.@*CONCLUSION@#The heterozygous c.2118delG (p.Lys706fs) frameshift mutation of the NIPBL gene probably underlies the CdLS in the fetus. Above finding has provided a basis for the genetic counseling for the family.


Subject(s)
Cell Cycle Proteins/genetics , DNA Mutational Analysis , De Lange Syndrome/pathology , Female , Fetus , Humans , Male , Mutation , Phenotype , Pregnancy , Whole Exome Sequencing
8.
Article in Chinese | WPRIM | ID: wpr-877646

ABSTRACT

OBJECTIVE@#To observe the clinical effect of electroacupuncture (EA) on aged insomnia, and explore its possible mechanism.@*METHODS@#A total of 60 patients with aged insomnia were randomly divided into an EA group (30 cases) and a sham EA group (30 cases, 1 case dropped off). The patients in the EA group were treated with acupuncture at Baihui (GV 20), Yintang (GV 29), Shenmen (HT 7), Sanyinjiao (SP 6), Xinshu (BL 15) and Shenshu (BL 23), and EA was used at Baihui (GV 20) and Yintang (GV 29), with intermittent wave, 2 Hz in frequency. In the sham EA group, the acupoints and the EA connection acupoints were the same as those in the EA group, 2-3 mm in depth, but no current was connected. The intervention was given 30 min each time, once every other day, 3 times a week for 4 weeks in the both groups. Before and after treatment, the Pittsburgh sleep quality index (PSQI) and Montreal cognitive assessment (MoCA) scale were used to assess sleep quality and cognitive function, and serum melatonin (MT) and dopamine (DA) levels were detected.@*RESULTS@#After treatment, the total score and sub-item scores of PSQI in the EA group were lower than those before treatment (@*CONCLUSION@#Electroacupuncture can improve sleep quality and cognitive function in aged insomnia patients, and its mechanism may be related to regulating serum MT and DA levels.


Subject(s)
Acupuncture Points , Aged , Dopamine , Electroacupuncture , Humans , Melatonin , Sleep Initiation and Maintenance Disorders/therapy
9.
Article in Chinese | WPRIM | ID: wpr-888182

ABSTRACT

A spectrum-activity relationship is established with high performance liquid chromatography(HPLC) fingerprints and the in vitro antioxidant activity to improve the quality evaluation system of Aralia taibaiensis. The HPLC profiles of 12 batches of samples were collected, and the similarity evaluation, heat map analysis and principal component analysis were conducted for the chemometric study of the fingerprint data. Combined with grey correlation analysis, the contributions of the common peaks in the fingerprints to the antioxidant activity were clarified, and the important peaks reflecting the efficacy were identified. The results showed that 17 common peaks were found in 12 batches of A. taibaiensis samples, and 6 of them were identified as saponins. Similarity evaluation, heat map analysis and principal component analysis roughly classified the A. taibaiensis herbs into two categories, i.e.,(1) S1-S10, S12 and(2) S11. Twelve batches of samples showed different antioxidant activities in a dose-dependent manner. In particular, S9 had the strongest antioxidant activity, while S11 was the weakest in antioxidant capacity, which was basically consistent with the overall score results. The results of grey correlation analysis demonstrated that the 17 common peaks scavenged DPPH radicals in the following order: X_3>X_(17)>X_4>X_8>X_7>X_(13)>X_2>X_6>X_(11)>X_(10)>X_(16)>X_(12)>X_9>X_5>X_(14)>X_1>X_(15), and scavenged ABTS radicals in the order of X_4>X_3>X_7>X_8>X_2>X_(17)>X_(13)>X_6>X_(16)>X_(11)>X_5>X_(12)>X_(10)>X_9>X_(14)>X_1>X_(15). Among them, X_3, X_4, X_7(araloside C), X_8 and X_(17) were the important peaks reflecting the efficacy of A. taibaiensis, which were basically consistent with those contained in the principal component 1. In this study, the correlation between the HPLC fingerprints of 12 batches of A. taibaiensis and its antioxidant activity provides a reference for the Q-marker screening and quality control of A. taibaiensis.


Subject(s)
Antioxidants , Aralia , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Saponins
10.
Article in Chinese | WPRIM | ID: wpr-888148

ABSTRACT

This study explored the in vivo effects and mechanisms of the modern classical prescription Supplemented Gegen Qinlian Decoction Formula(SGDF) against diabetic kidney disease(DKD). Sixty rats were randomly divided into the normal group, model group, SGDF group, and rosiglitazone(ROS) group. The modified DKD rat model was established by employing the following three methods: exposure to high-fat diet, unilateral nephrectomy, and intraperitoneal injection of streptozotocin(STZ). After modeling, rats in the four groups were treated with double distilled water, SGDF suspension, and ROS suspension, respectively, by gavage every day. At the end of the 6 th week of drug administration, all the rats were sacrificed for collecting urine, blood, and kidney tissue, followed by the examination of rat general conditions, urine and blood biochemical indicators, glomerulosclerosis-related indicators, podocyte pyroptosis markers, insulin resistance(IR)-related indicators, and key molecules in the insulin receptor substrate(IRS) 1/phosphatidylinositol-3-kinase(PI3 K)/serine threonine kinase(Akt) signaling pathway. The results showed that SGDF and ROS improved the general conditions, some renal function indicators and glomerulosclerosis of DKD model rats without affecting the blood glucose(BG). Besides, they ameliorated the expression characteristics and levels of podocyte pyroptosis markers, alleviated IR, and up-regulated the protein expression levels of the key molecules in IRS1/PI3 K/Akt pathway to varying degrees. In conclusion, similar to ROS, SGDF relieves DKD by targeting multiple targets in vivo. Specifically, it exerts the therapeutic effects by alleviating podocyte pyroptosis and IR. This study has preliminarily provided the pharmacological evidence for the research and development of new drugs for the treatment of DKD based on SGDF.


Subject(s)
Animals , Diabetes Mellitus , Diabetic Nephropathies/drug therapy , Drugs, Chinese Herbal , Insulin Resistance , Podocytes , Pyroptosis , Rats
11.
Article in Chinese | WPRIM | ID: wpr-912481

ABSTRACT

Objective:To investigate the diagnostic and prognostic value of the growth differentiation factor 15 (GDF15) and the procalcitonin (PCT) in sepsis.Methods:A total number of 137 patients with sepsis (considered as the sepsis group) and 59 patients with inflammatory infection but not diagnosed as sepsis (the non-sepsis group) received treatment in intensive care unit of Renming Hospital of Wuhan University were collected from July 2020 to January 2021, and 62 cases of healthy physical examination (control group) were simultaneously chosen as control. Sepsis patients were divided into two groups (death group [ n=48] and survival group [ n=89]) according to their 28-day′s survival. The serum levels of GDF15, PCT, C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-10 (IL-10) were examined, and the levels of each index, was dynamically monitored on the 1st, 3rd and 7th day after admission. The differences of the two indicators between different groups were compared by non-parametric test. The correlation between GDF15 and PCT was analyzed by Spearman correlation test. The receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic and prognostic value of the two indicators for sepsis. Results:The levels of GDF15 in the sepsis group, non-sepsis group and control group were 3.22 (1.39, 6.31) μg/L, 0.84 (0.21, 1.66) μg/L and 0.11 (0.09, 0.13) μg/L, respectively. The levels of PCT were 13.10 (1.99, 50.25) μg/L, 0.24 (0.13, 0.68) μg/L and 0.05 (0.03, 0.10) μg/L, respectively. The levels of CRP were 115.80 (26.40, 184.07) mg/L, 24.20 (11.30, 53.20) mg/L and 0.50 (0.50, 2.76) mg/L, respectively. The levels of IL-6 were 68.26 (21.59, 255.46) ng/L, 33.20 (10.81, 89.27) ng/L and 8.82 (7.33, 11.23) ng/L, respectively. The levels of IL-10 were 11.30 (5.88, 25.50) ng/L, 9.34 (5.65, 16.90) ng/L and 4.94 (4.31, 5.31) ng/L, respectively. The GDF15, PCT, CRP and IL-6 of the sepsis group were significantly higher than those of the non-sepsis group (The U values were 67.681, 86.034, 44.164 and 38.934, respectively, with P values less than 0.05) and the control group (The U values were 136.475, 138.667, 120.701 and 100.886, respectively, with P values less than 0.001). There was no significant difference in IL-10 between sepsis group and nonsepsis group, but it was higher than that of control group ( U=80.221, P<0.001). There was a positive correlation between GDF15 and PCT in patients with sepsis, and the spearman correlation coefficient was 0.234 ( P=0.006). The GDF15 of the death group and the survival group were 5.49 (3.60, 8.25) μg/L and 2.03 (1.06, 3.69) μg/L, and the PCT levels were 26.45 (11.23, 94.25) μg/L and 9.08 (1.33, 22.75) μg/L, respectively. GDF15 and PCT in the death group were significantly higher than those in the survival group ( U values were 3 305.500 and 3 060.000, respectively, and P values were both less than 0.001). The GDF15 and PCT levels in the death group were higher than those in the survival group on the 1st, 3rd and 7th day of dynamic monitoring ( P<0.05), however, the level of CRP and IL-10 were not significantly different ( P>0.05). The level of IL-6 in the death group was not significantly different from that of the death group on 1st day, but was higher than that of the survival group on the 3rd and 7th day ( P<0.05). The area under the curve (AUC) of GDF15, PCT, CRP, IL-6 and IL-10 alone and in the combined diagnosis of sepsis were 0.899, 0.938, 0.874, 0.789, 0.698 and 0.962, respectively. The combined detection of AUC was better than a single index; the GDF15, PCT, CRP, IL-6 and IL-10 alone and combined detection of sepsis prognosis AUC were 0.774, 0.716, 0.522, 0.623, 0.520 and 0.839, respectively, the combined detection of AUC is also better than single index. Conclusions:GDF15 and PCT have good clinical reference value in the differential diagnosis and prognosis of sepsis. The combination of indicators has a higher clinical value. GDF15 may become a biomarker for the diagnosis and prognosis of sepsis.

12.
Article in Chinese | WPRIM | ID: wpr-912372

ABSTRACT

Glucocorticoids (GCS) are the main treatment for non-infectious uveitis (NIU). However, long-term GCS treatment may induce systemic side effects including hypertension, hyperlipidemia and diabetes. Patients may develop cataract, ocular hypertension or glaucoma because of topical application of GCS. Rapamycin (RAPA) exhibits immunosuppressive, antiangiogenic and antiproliferative effects. Animal experiments and clinical trials have shown that RAPA has therapeutic potential for NIU, especially the treatment of intravitreal injection. In particular, intravitreal injection of RAPA can result in minimal systemic exposure and reduce adverse events. Meanwhile, systemic unwanted effects should be concerned about. In recent years, some studies have attempted to employ nanostructured carriers to improve penetrating abilities of RAPA and efficacy of treatment for ocular posterior segment diseases. These carriers include micelles, liposomes, nanocrystals, polymeric nanoparticles, magnetic nanoparticles and so on. Whether they can load RAPA for treating NIU deserves further study and exploration.

13.
Article in Chinese | WPRIM | ID: wpr-910546

ABSTRACT

Objective:To analyze the efficacy and prognostic factors of induced chemotherapy combined with radiotherapy in the treatment of early stage extranodal natural-killer/T cell lymphoma (ENKTCL).Methods:Two hundred and eighty-seven early stage NKTCL patients were treated in Affiliated Cancer Hospital of Guizhou Medical University from October 2003 to October 2021. All patients were aD ministrated with short courses of induced chemotherapy combined with radiotherapy. Clinical prognostic factors of early stage NKTCL were analyzed. The overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan- Meier method, log-rank test was conducted for univariate analysis and Cox models were performed for multivariate analysis. Results:The 5-year OS and PFS were 72.8% and 68.9% in all patients. According to Nomogram risk index (NRI) prognostic model, 286 patients were divided into the low risk (NRI=0), intermediate low risk (NRI=1), intermediate high risk (NRI=2), high risk (NRI=3) and very high risk (NRI≥4) groups. In these 5 groups, the 5-year OS were 95.6%, 76.3%, 69.5%, 61.0% and 23.3%(all P<0.001), and the 5-year PFS were 93, 2%, 69.8%, 64.6%, 60.2% and 23.3%(all P<0.001), respectively. In the radiotherapy with a dose of ≥50 Gy and<50 Gy groups, the 5-year OS were 73.8% and 65.9%( P=0.123) and the 5-year PFS were 72.8% and 45.3%( P=0.001). According to the response to induced chemotherapy of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD), the 5-year OS were 85.4%, 74.0%, 61.8% and 28.5%(all P<0.001), and the 5-year PFS were 83.7%, 66.8%, 65.7% and 27.4%(all P<0.001), respectively. Univariate analyses showed that stage Ⅱ, ECOG≥2, primary tumor invasion, radiotherapy dose<50 Gy and short-term efficacy of induced chemotherapy were poor prognostic factors for the 5-year OS and PFS (all P<0.05). Multivariate analyses demonstrated that primary tumor invasion, ECOG≥2 and stage Ⅱ were poor prognostic factors for OS (all P<0.05), and primary tumor invasion and ECOG≥2 were poor prognostic factors for PFS (all P<0.05). Conclusions:Early stage NKTCL patients can obtain high efficacy after induced chemotherapy combined with radiotherapy. Complete response to induced chemotherapy is associated with favorable prognosis.

14.
Article in Chinese | WPRIM | ID: wpr-908805

ABSTRACT

Objective:To investigate the expression of glypican1 (GPC1) in pancreatic ductal adenocarcinoma (PDAC) and its relationship with the prognosis of patients with PDAC.Methods:From January 2015 to December 2018, 125 PDAC tumor specimens and corresponding para-carcinoma normal pancreatic tissue were collected from the Department of Pathology of Peking University Third Hospital. The expression of GPC1 protein was detected by the immunohistochemical Envision two-step method in all specimens. The specimens were divided into high and low GPC1 expression groups according to immunohistochemical scores, and the correlation between GPC1 protein expression and clinicopathological features and overall survival time was analyzed.Results:The positive expression rate of GPC1 protein was 0 score in 30.4% of PDAC tissues, 1 score in 15.2%, 2 score in 18.4% and 3 score in 36.0%, respectively, and high expression rate (2+ 3) was 54.4%. GPC1 protein was negatively expressed in para-carcinoma pancreatic tissues. The positive expression rate of GPC1 protein in PDAC tissue was significantly higher than that in para-carcinoma pancreatic tissue, and the difference was statistically significant ( P=0.000). The high expression of GPC1 protein was significantly correlated with tumor location and T stage ( P<0.05), but not with gender, age, history of diabetes and pancreatitis, preoperative blood CA19-9 level, postoperative surgical margin, tumor differentiation, lymph node metastasis, nerve invasion and vascular invasion (all P values >0.05). Univariate Cox proportional hazards analysis showed that GPC1 expression was associated with postoperative overall survival time in PDAC patients ( P<0.001). Multivariate Cox proportional hazards analysis showed that GPC1 protein expression level was an independent prognostic factor affecting overall survival time in PDAC patients ( P<0.001). The median survival time of PDAC patients with high GPC1 expression was significantly lower than that of PDAC patients with low GPC1 expression (11.00 months vs 18.00 months), and the difference was statistically significant ( P<0.01). Conclusions:GPC1 protein was abnormally high expressed in PDAC tumor tissue, and the high expression of GPC1 protein was positively correlated with tumor stage and negatively correlated with the overall survival time of patients. High expression of GPC1 was an independent risk factor for poor prognosis in PDAC patients.

15.
Article in Chinese | WPRIM | ID: wpr-908614

ABSTRACT

Objective:To explore the therapeutic effects of intravenous injection of small extracellular vesicles (sEVs) derived from human umbilical cord mesenchymal stem cells (MSCs) on experimental autoimmune uveitis (EAU) in mice.Methods:MSCs from human umbilical cord were cultured and the supernatant was collected.The sEVs were isolated by ultracentrifugation method and a NanoSight instrument was used to analyze the particle size.The expression of surface markers sEVs, CD9, CD81 and CD63 was determined via Western blot.The morphology of sEVs was observed with a transmission electron microscope.Forty-eight 7-week-old female C57BL/6 mice were seclected to establish the EAU model through immunization with interphotoreceptor retinoid-binding protein peptide 651-670 (IRBP 651-670). The mice were divided into sEVs treatment group and phosphate buffer solution (PBS) control group using a random number table, with 24 mice in each group.The mice in the sEVs treatment group were injected with 50 μg of MSCs-derived sEVs via tail vein on the 11th day after modeling.In the PBS control group, the mice were injected with the same volume of PBS.Six mice in each group were randomly selected to observe the inflammation of the retina after mydriasis with an ophthalmoscope every other day from 8th day following modeling and the inflammation scores were evaluated.Six mice were randomly selected and sacrificed on the 14th day and 6 on the 18th day following modeling in each group, and both eyeballs of the mice were enucleated.Retinal tissue sections of the 6 mice sacrificed on the 18th day were stained with hematoxylin-eosin and the pathological scores were evaluated.The infiltration of helper T 1 (Th1) cells and Th17 cells in the eyeballs of the 6 mice sacrificed on the 18th day following modeling was detected by flow cytometry.T cells were isolated from spleen and lymph nodes of the 6 mice sacrificed on the 14th day, and the proliferation of T cells under different concentrations of IRBP 651-670 (0, 1, 10 and 20 μg/ml) was detected using a 5-bromodeoxyuridine (BrdU) method.To further study the effects of MSCs-derived sEVs on Th1/Th17 cells differentiation, naive T cells of spleen from another 3 normal mice were isolated by magnetic bead negative sorting and incubated with 10 μg/ml MSCs-derived sEVs or 10 μg/ml PBS, and then were cultured under Th1/Th17 cell differentiation conditions, respectively.Flow cytometry was used to measure the differentiation of naive T cells into Th1/Th17 cells.This study protocol complied with the regulations of the care and use of laboratory animals in China and was approved by an Ethics Committee of Tianjin Medical University (No.TJYY2019103022). Results:The isolated human MSCs-derived sEVs was with an average diameter of (102.4±33.6) nm and showed a double-layer membrane vesicle structure under the transmission electron microscope.The CD9, CD63 and CD81 proteins were highly expressed in sEVs.The inflammation scores of the sEVs treatment group were significantly lower than those in the control group on day 14, 16, 18, 20 and 22 after modeling (all at P<0.05). The pathological score of mice in the sEVs treatment group was significantly lower than that of PBS control group on the 18th day following modeling ( P<0.05). The flow cytometry results showed that on day 18 after modeling, the proportions of Th1 and Th17 cells in eyeballs in the sEVs treatment group were (15.55±2.03)% and (15.67±2.15)%, respectively, which were significantly lower than (21.35±0.72)% and (20.90±1.10)% in the PBS control group ( t=6.58, 5.31; both at P<0.01). BrdU results showed that when the IRBP 651-670 concentration was 20 μg/ml, the T cell proliferation ability in the sEVs treatment group was inhibited obviously compared with the control group ( P<0.05). The proportions of naive T cells differentiated into Th1 cells and Th17 cells in the sEVs treatment group were (28.15±1.32)% and (11.60±2.23)% respectively, which were significantly lower than (31.58±1.75)% and (23.52±1.76)% of the PBS control group, and the differences were statistically significant ( t=3.93, 10.26; both at P<0.05). Conclusions:Intravenous injection of human umbilical cord MSCs-derived sEVs can reduce the inflammation in EAU mice.The mechanism may be related to inhibiting the differentiation of naive T cells to Th1 and Th17 cells, and reducing the infiltration of Th1 and Th17 cells in the eyeballs.

16.
Article in Chinese | WPRIM | ID: wpr-906356

ABSTRACT

Objective:To explore the effects of Shenwei Ningyu pills (SNP), a new Chinese medicine for depression, on the immunoinflammatory response mediated by Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway in the hippocampus of rats exposed to chronic restraint stress (CRS). Method:Forty-four male Sprague Dawley rats were randomly enrolled into a normal group, a model group, an escitalopram group, and an SNP group. Except for the rats in the normal group, all rats were exposed to CRS and isolated rearing for 21 days continuously. Rats in the escitalopram group and the SNP group were administered with escitalopram (30 mg·kg<sup>-1</sup>) and SNP (18 mg·kg<sup>-1</sup>) one hour prior to CRS, respectively. The changes in body weight, sucrose preference index, horizontal movement scores, and vertical movement scores were observed by body weight assessment, sucrose preference test, and open field test. The expression of hippocampal TLR4 and MyD88 was detected by Western blot. The content of serum interleukin-1<italic>β</italic> (IL-1<italic>β</italic>), IL-10, and tumor necrosis factor-<italic>α</italic> (TNF-<italic>α</italic>) was detected by enzyme-linked immunosorbent assay (ELISA). Result:The results of the behavioral assessment showed that there was no significant difference in the changes of behavioral baselines among the groups before intervention. However, significant differences were found among the groups following different interventions. The body weight, sugar preference index, horizontal movement score, and vertical movement score of rats in the model group decreased after CRS for 21 days as compared with those in the normal group (<italic>P</italic><0.01). The above indicators in the SNP<italic> </italic>group and the escitalopram group were higher than those in the model group (<italic>P</italic><0.01), which indicated that SNP<italic> </italic>exerted an obvious antidepressant effect. The results of Western blot and ELISA showed that compared with the normal group, the model group showed elevated levels of hippocampal TLR4 and MyD88 and serum IL-1<italic>β</italic> and TNF-<italic>α </italic>(<italic>P</italic>˂0.01) and dwindled serum IL-10 (<italic>P</italic>˂0.01), while SNP<italic> </italic>and escitalopram reversed the conditions in the model group (<italic>P</italic>˂0.01) except for TNF-<italic>α</italic>. Conclusion:The present study indicated that the antidepressant effect of SNP was presumedly achieved by inhibiting the immunoinflammatory response mediated by the TLR4/Myd88 signaling pathway in CRS rats.

17.
Acta Pharmaceutica Sinica ; (12): 1409-1415, 2021.
Article in Chinese | WPRIM | ID: wpr-887074

ABSTRACT

Compound houttuynia mixture belongs to OTC class A medicine, which is made from Houttuynia cordata, Scutellaria baicalensis, Radix Isatidis, Forsythia, and Lonicera. As a kind of compound preparation of traditional Chinese medicine, houttuynia cordata mixture has extensive pharmacological effects, for example, clearing away heat and detoxifying, thus it is used for the sore throat, acute pharyngitis, and tonsillitis with wind-heat syndrome. In this study, the antiviral activity against influenza viruses and the primary mechanism of compound houttuynia mixture was evaluated. The antiviral effect of compound houttuynia mixture was determined by cytopathic effects (CPE), Western blot, quantitive reverse transcription PCR (qRT-PCR), and virus titer assays. The effect of houttuynia mixture on the replication cycle of influenza virus was evaluated by time-of-addition assay. In conclusion, the results showed that the compound houttuynia mixture had a broad-spectrum effect against influenza virus, including the international common influenza virus strains, the drug-resistant strains and the highly pathogenic avian influenza viruses H5N1 and H7N9. It mainly impairs the early stage of the viral replication.

18.
Acta Pharmaceutica Sinica ; (12): 1400-1408, 2021.
Article in Chinese | WPRIM | ID: wpr-887072

ABSTRACT

Qing-Fei-Pai-Du decoction (QFPDD) is a combination of traditional Chinese medicine and plays an important role in the treatment of coronavirus disease 2019 (COVID-19). This study investigated the inhibitory effect of QFPDD on coronavirus replication and antiviral mechanism. The cytotoxicity of QFPDD was determined by PrestoBlue cell viability assay. Quantitive reverse transcription PCR (qRT-PCR) and immunofluorescence assay (IF) were used to detect the inhibitory effects of QFPDD on coronavirus at RNA and protein levels. qRT-PCR was used to detect the adsorption and penetration of coronavirus after QFPDD treatment. The effects of QFPDD on interferon (IFN) and interferon-stimulated genes (ISGs) were also detected by qRT-PCR. The results showed that QFPDD inhibited coronavirus at RNA and protein levels in a dose-dependent manner at non-toxic concentration, and QFPDD targeted in the early stages of coronavirus infection cycle. Preliminary mechanism studies have shown that QFPDD can directly block the virus entry into the cell by inhibiting virus adsorption, and QFPDD can also play an antiviral role by up-regulating the expression of IFN and ISGs. These results indicate QFPDD as a drug potential to treat coronavirus infection.

19.
Article in Chinese | WPRIM | ID: wpr-885546

ABSTRACT

We describe the prenatal diagnosis and postnatal follow-up of a fetus with a pericallosal lipoma diagnosed by MRI. The pregnant woman was admitted to Zhongnan Hospital of Wuhan University in February 2019. MRI examinations with multiple sequences and imaging methods were performed prenatally at 31 +6 and 38 +3 weeks of gestation, and at two days and three months postnatally. The MRI images showed that the corpus callosum was normal and the lesion was located around the corpus callosum, with high signal intensity on T1 weighted imaging, medium-to-high signal intensity on T2 weighted imaging, and low signal intensity on fat suppression sequence. No abnormal blood vessels were found on susceptibility-weighted imaging and time-of-flight magnetic resonance angiography sequences. Based on the prenatal and postnatal MRI findings, the tumor was clinically diagnosed as a pericallosal lipoma.

20.
Journal of Chinese Physician ; (12): 797-800, 2021.
Article in Chinese | WPRIM | ID: wpr-884123

ABSTRACT

MicroRNAs (miRNAs) are a class of non coding small RNAs. MiRNAs can regulate cell signal transduction and gene expression, affect cell proliferation, apoptosis and other cell physiological processes, and play a crucial role in maintaining normal biological metabolism and homeostasis of the intracellular environment. In addition, miRNAs are widely involved in the occurrence and progress of cancer. Studies have shown that miRNA27a, a member of the miRNAs family, can play the role of oncogene or tumor suppressor gene in different cancer disease models. This article will review the expression, mechanism and potential clinical application of miRNA27a in different malignant tumors.

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