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1.
Article in Chinese | WPRIM | ID: wpr-940996

ABSTRACT

OBJECTIVE@#To explore potential categories of parental social support for young parents under the coronavirus disease 2019 (COVID-19) epidemic, and to examine correlations of different types of parents' social support with parental burnout.@*METHODS@#In April 2020, we conducted an online voluntary survey among young parents across China with scales and a self-designed questionnaire. The latent profile analysis method was used to analyze parents' received social support and perceived social support. The social support categories were taken as independent variables and parental burnout as dependent variables, and multiple regression analysis was carried out to explore the relationship between received social support, perceived social support and parental burnout. Finally, the moderating effect of resilience between social support groups and parental burnout was discussed.@*RESULTS@#The results of latent profile analysis revealed three potential types of received social support, namely isolate, normal, and multi-support and the proportions of the respondents with the three profiles were 14.1%, 78.0%, and 7.9%. Four potential types of perceived social support, namely, indigent, medium, affluent and divergent and the proportions of the respondents with the four profiles were 13.7%, 29.6%, 25.3%, and 31.3%. Among them, the parents with divergent perceived social support had more perception of social support from the couple, family and relatives, but less perception of social support from net-friend, social organizations and the government. Regression analysis showed that there was no statistically significant correlation between different profiles of received social support and parental burnout, and among the groups of perceived social support, there was a statistically significant correlation between indigent and divergent types of social support and parental burnout. The divergent parents had lower levels of parental burnout compared with indigent (β=-0.120, P=0.003). Also, resilience moderated the effect of divergent perceived social support and parental burnout. Compared with the parents with low resilience, the parents with high resilience perceived divergent social support with lower parenting burnout.@*CONCLUSION@#There are prominent latent types of received social support and perceived social support under epidemic. People with divergent perceived social support (more perceived supports from partner, family and friends) are prone to have a relatively lower risk of parental burnout. Parents with higher resilience will be more sensitive to the support of close acquaintances, and can better resist parental burnout.


Subject(s)
Burnout, Psychological/epidemiology , COVID-19/epidemiology , China/epidemiology , Humans , Parents , Social Support
2.
Chinese Journal of Cardiology ; (12): 549-555, 2022.
Article in Chinese | WPRIM | ID: wpr-940887

ABSTRACT

Objective: To investigate the acute and long-term outcome of catheter ablation for the treatment of ventricular tachycardia (VT) in patients with arrhythmogenic left ventricular cardiomyopathy (ALVC). Methods: This retrospective, cross-sectional study enrolled ALVC patients undergoing radiofrequency ablation for the treatment of VT at the First Affiliated Hospital of Nanjing Medical University from January 2011 to December 2018 and collected their clinical characteristics and intraoperative electrophysiological examination. Patients were followed up every 6 months after radiofrequency ablation until August 2021. Echocardiographic results and VT recurrence post radiofrequency ablation were analysed. Results: Totally 12 patients were enrolled (mean age: (42±15) years, 11 males(11/12)). The mean of left ventricular end diastolic diameter (LVDd) and left ventricular ejection fraction (LVEF) were (51±5)mm and (65±5)%, respectively. Twelve VTs were induced in 10 patients during the electrophysiological study, and the mean tachycardia cycle length was (293±65) ms. Three-dimensional substrate mapping revealed the diseased area at endocardial site in one patient, at epicardial sites in the other 11 patients (involved endocardial sites in 2 cases) with the basal part near the mitral annulus being the predilection for the substrate (10/11). After the catheter ablation at the endocardial and epicardial sites respectively, the complete procedure endpoint was achieved in all patients (VT cannot be induced post ablation). The median follow-up time was 65 (25, 123) months. One patient was lost to follow-up, and the other 11 patients survived without VT. No significant cardiac function deterioration was detected by the echocardiographic examination ((51±5)mm vs. (52±5)mm, P>0.05 for LVDd, (65±5)% vs. (60±6)%, P>0.05 for LVEF) at the end of follow-up. Conclusion: After radiofrequency ablation, the complete procedure endpoint is achieved in ALVC patients, and the catheter ablation provides long-term ventricular tachycardia control during the long-term follow-up.


Subject(s)
Adult , Cardiomyopathies , Catheter Ablation , Cross-Sectional Studies , Follow-Up Studies , Humans , Male , Middle Aged , Pericardium/surgery , Recurrence , Retrospective Studies , Stroke Volume , Tachycardia, Ventricular/surgery , Treatment Outcome , Ventricular Function, Left
3.
Article in Chinese | WPRIM | ID: wpr-940480

ABSTRACT

ObjectiveTo explore the mechanism of Liu Junzitang in preventing and treating muscle atrophy in mice with lung cancer cachexia based on the signal transducer and activator of transcription 3(STAT3)/ubiquitin proteasome pathway in vivo. MethodForty C57BL/6 mice aged six weeks were randomly divided into a blank group, a model group, a Liu Junzitang group, an inhibitor group (stattic group),and a Liu Junzitang + inhibitor group (combination group), with eight mice in each group. The cachectic muscle atrophy model was induced by subcutaneous inoculation of Lewis lung cancer cell line under the right anterior armpit in mice except those in the blank group. On the 8th day after subcutaneous inoculation, the mice in the corresponding groups received Liu Junzitang (9.56 g·kg-1·d-1) by gavage and intraperitoneal injection of stattic [25 mg·kg-1·(2 d)-1]. After three weeks of drug intervention, the body weight and gastrocnemius muscle weight were recorded. Hematoxylin-eosin (HE) staining was used to observe the pathological changes and cross-sectional area of gastrocnemius muscle fibers in mice. Western blot was used to detect the expression of phosphorylated-STAT3 (p-STAT3), STAT3, muscle atrophy F-box (MAFbx), and muscle RING finger protein 1 (MuRF1) in the gastrocnemius muscle. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of STAT3, MAFbx, and MuRF1 in the gastrocnemius muscle. ResultCompared with the blank group, the model group showed lightened body and the gastrocnemius muscle, reduced cross-sectional area of gastrocnemius muscle fibers, and increased protein expression of p-STAT3, STAT3, MAFbx, and MuRF1 and mRNA expression of STAT3, MuRF1, and MAFbx in the gastrocnemius muscle (P<0.05). Compared with the model group, the Liu Junzitang group showed increased body weight, gastrocnemius muscle weight, and cross-sectional area of gastrocnemius muscle fibers (P<0.05), and decreased protein expression of p-STAT3, STAT3, MuRF1, MAFbx, and mRNA expression of STAT3 and MAFbx in gastrocnemius muscle (P<0.05). Compared with the model group, the inhibitor group showed increased body weight and cross-sectional area of gastrocnemius muscle fibers (P<0.05), and reduced protein expression of p-STAT3, STAT3, MuRF1, MAFbx, and mRNA expression of STAT3 and MAFbx in gastrocnemius muscle (P<0.05). Compared with the model group, the combination group showed increased body weight and gastrocnemius muscle weight (P<0.05),and decreased protein expression of p-STAT3, STAT3, MuRF1, and mRNA expression of STAT3 and MAFbx in the gastrocnemius muscle (P<0.05). Compared with the Liu Junzitang group, the stattic group and the combination group showed reduced expression of p-STAT3 protein in the gastrocnemius muscle (P<0.05). ConclusionLiu Junzitang can prevent and treat muscle atrophy in mice with lung cancer cachexia, and its mechanism may be associated with the protein and mRNA expression related to the STAT3-mediated ubiquitin proteasome pathway.

4.
Article in Chinese | WPRIM | ID: wpr-940478

ABSTRACT

Andrographolide, a diterpene lactone, is the important material basis for the pharmacological effect of the Chinese medicinal Andrographis paniculata (Burm.f.)Nees. Modern pharmacological research has shown that andrographolide has many pharmacological activities such as anti-inflammation, bacteriostat, anti-virus, anti-tumor, protecting liver, promoting the function of gallbladder, and protecting the cardiovascular system and nervous system. It has significant anti-inflammatory activity which involves multiple targets. To be specific, it can inhibit nuclear factor-κB (NF-κB), signal transduction and activator of transcription 3 (STAT3), and other signaling pathways, reduce the synthesis and release of downstream inflammatory mediators, and regulate oxidative stress and immune response to achieve anti-inflammatory effect on various inflammatory diseases. At the same time, it suppresses a variety of tumor cells by inhibiting tumor cell proliferation, blocking cell cycle, and inducing tumor cell apoptosis. Its anti-tumor mechanism involves cellular signaling pathways such as Notch, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), NF-κB, and secreted glycoprotein/β-catenin (Wnt/β-catenin). In addition, it can also alleviate diabetes by regulating glucose metabolism. According to related research, it often exerts pharmacological effects through multiple pathways and multiple targets, but the specific targets are unclear. Therefore, this article summarizes the relevant studies on the pharmacological effects and mechanisms of andrographolide in the past three years and puts forward the future research directions, which is expected to serve as a reference for the further in-depth research and development and utilization of andrographolide.

5.
Article in Chinese | WPRIM | ID: wpr-940379

ABSTRACT

The incidence and mortality of cancer are increasing year by year, seriously threatening human health. At present, the chemotherapy-based treatment of cancer can prolong the survival time of patients, but its severe side effects and adverse reactions often lead to poor prognosis. Therefore, searching for anti-cancer drugs with high efficiency and low toxicity has become the focus of clinical attention from all over the world. The effective components of Chinese medicine have the advantages of mild side effect and multi-target regulation, and their anti-tumor activities are highly favored by many researchers. Shikonin, a naphthoquinone compound, is the main effective component of Arnebiae Radix, with anti-tumor, anti-inflammatory, antioxidant, and other pharmacological effect. Studies have shown that shikonin possesses significant anti-tumor activities against a variety of tumor cells, and it can inhibit the development of many cancers, such as breast cancer, lung cancer, liver cancer, cervical cancer, ovarian cancer, colon cancer, and prostate cancer. The anti-tumor mechanism of shikonin is mainly related to multi-pathway and multi-target inhibition of tumor cell proliferation, the promotion of reactive oxygen species (ROS) production, induction of tumor cell apoptosis, cell cycle arrest, and tumor cell autophagy, and the inhibition of tumor cell migration and invasion. In addition, shikonin can increase the sensitivity of tumor cells to anti-tumor drugs and reverse the drug resistance of tumor cells. The signaling pathways involved in the anti-tumor effect of shikonin include phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), PI3K/Akt/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), pyruvate kinase M2/signal transducer and activator of transcription protein 3 (PKM2/STAT3), and Kelch-like epichlorohydrin-related protein 1/nuclear factor E2-related factor 2 (Keap1/Nrf2). The anti-tumor effects are mainly achieved through the regulation of the PI3K/Akt signaling pathway. Based on the relevant literature on the anti-tumor effect and mechanism of shikonin in China and abroad, the present study reviewed the research progress in the past three years to provide useful references for the further study of the anti-tumor effect of shikonin and the research and development of new antineoplastic drugs.

6.
Article in English | WPRIM | ID: wpr-939774

ABSTRACT

OBJECTIVE@#To explore the molecular bases of Chinese medicine (CM) syndrome classification in chronic hepatitis B (CHB) patients in terms of DNA methylation, transcription and cytokines.@*METHODS@#Genome-wide DNA methylation and 48 serum cytokines were detected in CHB patients (DNA methylation: 15 cases; serum cytokines: 62 cases) with different CM syndromes, including dampness and heat of Gan (Liver) and gallbladder (CHB1, DNA methylation: 5 cases, serum cytokines: 15 cases), Gan stagnation and Pi (Spleen) deficiency (CHB2, DNA methylation: 5 cases, serum cytokines: 15 cases), Gan and Shen (Kidney) yin deficiency (CHB3, DNA methylation: 5 cases, serum cytokines: 16 cases), CHB with hidden symptoms (HS, serum cytokines:16 cases) and healthy controls (DNA methylation: 6 cases). DNA methylation of a critical gene was further validated and its mRNA expression was detected on enlarged samples. Genome-wide DNA methylation was detected using Human Methylation 450K Assay and furthered verified using pyrosequencing. Cytokines and mRNA expression of gene were evaluated using multiplex biometric enzyme-linked immunosorbent assay (ELISA)-based immunoassay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively.@*RESULTS@#Totally 28,667 loci, covering 18,403 genes were differently methylated among CHB1, CHB2 and CHB3 (P<0.05 and |Δβ value| > 0.17). Further validation showed that compared with HS, the hg19 CHR6: 29691140 and its closely surrounded 2 CpG loci were demethylated and its mRNA expressions were significantly up-regulated in CHB1 (P<0.05). However, they remained unaltered in CHB2 (P>0.05). Levels of Interleukin (IL)-12 were higher in CHB3 and HS than that in CHB1 and CHB2 groups (P<0.05). Levels of macrophage inflammatory protein (MIP)-1α and MIP-1β were higher in CHB3 than other groups and leukemia inhibitory factor level was higher in CHB1 and HS than CHB2 and CHB3 groups (P<0.05). IL-12, MIP-1α and MIP-1β concentrations were positively correlated with human leukocyte antigen F (HLA-F) mRNA expression (R2=0.238, P<0.05; R2=0.224, P<0.05; R=0.447, P<0.01; respectively). Furthermore, combination of HLA-F mRNA and differential cytokines greatly improved the differentiating accuracy among CHB1, CHB2 and HS.@*CONCLUSIONS@#Demethylation of CpG loci in 5' UTR of HLA-F may up-regulate its mRNA expression and HLA-F expression was associated with IL-12, MIP-1α and MIP-1β levels, indicating that HLA-F and the differential cytokines might jointly involve in the classification of CM syndromes in CHB.@*REGISTRATION NO@#ChiCTR-RCS-13004001.


Subject(s)
Chemokine CCL3/genetics , Chemokine CCL4/genetics , Cytokines/genetics , DNA Methylation/genetics , HLA Antigens , Hepatitis B, Chronic/genetics , Histocompatibility Antigens Class I , Humans , Interleukin-12/genetics , Medicine, Chinese Traditional , RNA, Messenger , Syndrome
7.
Acta Physiologica Sinica ; (6): 479-488, 2022.
Article in Chinese | WPRIM | ID: wpr-939582

ABSTRACT

Cell aging is an extremely complex process, which is characterized by mitochondrial structural dysfunction, telomere shortening, inflammatory microenvironment, protein homeostasis imbalance, epigenetic changes, abnormal DNA damage and repair, etc. Aging is usually accompanied by structural and functional damage of tissues and organs which further induces the occurrence and development of aging-related diseases. Aging includes physiological aging caused by increased age and pathological aging induced by a variety of factors. Noteworthy, as a target organ directly contacting with the outside air, lung is more prone to various stimuli, causing pathological premature aging which is lung aging. Studies have found that there is a certain proportion of senescent cells in the lungs of most chronic respiratory diseases. However, the underlying mechanism by which these senescent cells induce lung senescence and their role in chronic respiratory diseases is still obscure. This paper focuses on the causes and classification of lung aging, the internal mechanism of lung aging involved in chronic respiratory diseases, and the application of anti-aging treatments in chronic respiratory diseases. We hope to provide new research ideas and theoretical basis for the clinical prevention and treatment in chronic respiratory diseases.


Subject(s)
Aging/pathology , Cellular Senescence , Humans , Lung/pathology , Lung Diseases/pathology , Respiration Disorders/pathology , Telomere , Telomere Shortening
8.
Article in Chinese | WPRIM | ID: wpr-936086

ABSTRACT

Objective: To analyze the association of No.11p posterior lymph node metastasis with clinicopathological features and its prognostic significance in gastric cancer. Methods: A single-center retrospective cohort study was conducted. Clinicopathological data of patients with primary gastric cancers undergoing No.11p posterior lymph node dissection from January 2016 to December 2020 were retrieved from the Database of Gastric Cancer, West China Hospital, Sichuan University. Case inclusion criteria: (1) gastric cancer proved by pathology; (2) radical resection with intraoperative No.11p posterior lymph node dissection; (3) operations performed by the same surgical team; (4) no previous history of other malignant tumors and no concurrent malignant tumors. Those with stump gastric cancer, history of gastrectomy, neoadjuvant chemotherapy, incomplete clinicopathological data and lost to follow-up were excluded. During the operation, the upper edge of the pancreas was retracted forward to expose the area between the upper edge of the pancreas and the splenic vessels. The proximal segment of the splenic artery was skeletonized to remove lymphatic tissue anterior and superior to the splenic artery for No.11p lymph node dissection. For patients with lymphadenopathy in the area between the splenic artery and the splenic vein, dissection was performed. The enlarged lymph nodes were labeled with titanium clips and named as No.11p posterior lymph node. Pathological examination was performed separately after the specimen was isolated. Statistical analysis was performed using R software. Results: A total of 127 gastric cancer patients, who underwent No.11p posterior lymph nodes dissection were included in this study, of which 120 patients without No.11p posterior lymph nodes metastasis (No.11p posterior lymph nodes negative) and 7 patients with No.11p posterior lymph nodes metastasis (No.11p posterior lymph nodes positive). A total of 8 metastatic No.11p posterior lymph nodes were detected in 7 patients, metastasis rate and with a ratio of 5.5% (7/127) and 6.8% (8/127), respectively. In the subgroup analysis of T3-4 stage patients, the metastasis rate and ratio of No.11p posterior lymph nodes were 9.0% (7/78) and 10.7% (8/75), respectively. Compared to negative cases, patients with No.11p posterior lymph nodes metastasis had larger tumor (P=0.002), higher proportion of Borrmann type Ⅲ and Ⅳ tumors (P=0.005), more metastatic lymph nodes (P<0.001), more advanced T stage (P=0.043), N stage (P=0.004) and TNM stage (P=0.015). In survival analysis, patients with No.11p posterior lymph node metastasis had a significantly worse prognosis than those without metastasis after adjusting for TNM stage (hazard ratio=3.009, 95% confidence interval: 1.824-4.964, P<0.001). Conclusions: The No.11p posterior lymph node metastasis in gastric cancer is associated with worse prognosis. For patients of T3-4 stage gastric cancer, No.11p posterior lymph node dissection should be emphasized during radical operation.


Subject(s)
Gastrectomy , Humans , Lymph Node Excision , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Prognosis , Retrospective Studies , Stomach Neoplasms/pathology
9.
Chinese Journal of Pediatrics ; (12): 215-220, 2022.
Article in Chinese | WPRIM | ID: wpr-935673

ABSTRACT

Objective: To understand the current situation regarding pediatric off-label use of drugs recommendations in Chinese clinical practice guidelines and to make recommendations for standardized reporting format regarding off-label use of drugs for children. Methods: This cross-sectional study was carried out by systematically searching the databases for Chinese guideline consensus articles published in journals between 2018 and 2020 and extracting recommendations regarding off-label use of drugs from those articles. The essential characteristics of the included guidelines, the ranking of off-label drug types, the order of drug information, the type of off-label drug use, and the percentage of citation studies on which the recommendations were based were analyzed. Results: Among 108 studies that included Chinese off-label guidelines and consensus, 364 recommendations on pediatric off-label use of drugs were included. The Chinese Medical Association published the most, 48 out of the 108 studies (44.4%), and of those 14 studies (13.0%) were on infectious and parasitic diseases. Of the 364 recommendations on off-label use of drugs, the most commonly addressed drugs were 16 recommendations (4.4%) for cyclosporine A, 11 recommendations (3.0%) for methotrexate , and 11 recommendations (3.0%) for fentanyl. The most commonly addressed drug categories were as follows: 68 recommendations (18.6%) were immune system drugs, 66 recommendations (18.1%) were anti-infectives, and 56 recommendations (15.4%) were oncology drugs. The most commonly addressed drug information accounts were as follows: 364 recommendations (100.0%) were indications, 204 recommendations (56.0%) were dosages, and 198 recommendations (54.4%) were the route of administration. Based on the instructions approved by the Chinese Food and Drug Administration, the main forms of the off-label drug were as follows: 175 recommendations (48.1%) were unapproved indications, 127 recommendations (34.9%) were unapproved populations, and 72 recommendations (19.8%) were unapproved ages. Only 129 recommendations (35.4%) were cited, mainly including clinical guidelines (48 studies, 23.4%), reviews (22 studies, 10.7%), and pediatric randomized controlled trials (22 studies, 10.7%). Conclusions: Off-label use of drugs is commonly recommended in pediatric guidelines and consensus documents written by Chinese authors. However, the reporting of the recommendations varies widely, and the quality of the supporting evidence is poor.


Subject(s)
Child , China , Consensus , Cross-Sectional Studies , Humans , Off-Label Use , Pharmaceutical Preparations
10.
Chinese Journal of Pathology ; (12): 307-313, 2022.
Article in Chinese | WPRIM | ID: wpr-935531

ABSTRACT

Objective: To analyze the genetic landscape of 52 fusion genes in patients with de novo acute lymphoblastic leukemia (ALL) and to investigate the characteristics of other laboratory results. Methods: The fusion gene expression was retrospectively analyzed in the 1 994 patients with de novo ALL diagnosed from September 2016 to December 2020. In addition, their mutational, immunophenotypical and karyotypical profiles were investigated. Results: In the 1 994 patients with ALL, the median age was 12 years (from 15 days to 89 years). In the panel of targeted genes, 15 different types of fusion genes were detected in 884 patients (44.33%) and demonstrated a Power law distribution. The frequency of detectable fusion genes in B-cell ALL was significantly higher than that in T-cell ALL (48.48% vs 18.71%), and fusion genes were almost exclusively expressed in B-cell ALL or T-cell ALL. The number of fusion genes showed peaks at<1 year, 3-5 years and 35-44 years, respectively. More fusion genes were identified in children than in adults. MLL-FG was most frequently seen in infants and TEL-AML1 was most commonly seen in children, while BCR-ABL1 was dominant in adults. The majority of fusion gene mutations involved signaling pathway and the most frequent mutations were observed in NRAS and KRAS genes. The expression of early-stage B-cell antigens varied in B-cell ALL patients. The complex karyotypes were more common in BCR-ABL1 positive patients than others. Conclusion: The distribution of fusion genes in ALL patients differs by ages and cell lineages. It also corresponds to various gene mutations, immunophenotypes, and karyotypes.


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Gene Expression , Genes, ras , Humans , Infant , Infant, Newborn , Middle Aged , Oncogene Fusion , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Retrospective Studies , Young Adult
11.
Article in Chinese | WPRIM | ID: wpr-933328

ABSTRACT

Objective:To evaluate the effect of electrical stimulation on lipopolysaccharide (LPS)-induced activation of M1 microglia.Methods:The well-growing BV2 microglia cells were divided into 3 groups ( n=18 each) using a random number table method: control group (group C), group LPS, LPS and electrical stimulation group (group LE). The cells were cultured for 24 h in normal culture atmosphere in group C. In group LPS and group LE, the LPS medium culture 100 ng/ml was added, and the cells were cultured for 24 h. In group LE, cells were stimulated with 100 mV/mm direct current for 4 h before LPS incubation.The levels of tumor necrosis factor-α (TNF-α) and leukocyte interleukin-1β (IL-1β) were determined by enzyme-linked immunosorbent assay.The expression of the M1 microglia surface markers CD32 and inducible nitric oxide synase (iNOS) was detected using immunofluorescent staining.The expression of CD32 and iNOS mRNA was detected using quantitative real-time polymerase chain reaction. Results:Compared with group C, the concentrations of TNF-α and IL-1β were significantly increased, and the expression of CD32 and iNOS protein and mRNA was up-regulated in LPS and LE groups ( P<0.05). Compared with group LPS, the concentrations of TNF-α and IL-1β were significantly decreased, and the expression of CD32 and iNOS protein and mRNA was down-regulated in group LE ( P<0.05). Conclusions:Electrical stimulation can inhibit LPS-induced activation of M1 microglia and thus alleviate the inflammatory responses.

12.
Chinese Journal of Geriatrics ; (12): 158-161, 2022.
Article in Chinese | WPRIM | ID: wpr-933051

ABSTRACT

Objective:To evaluate the predictive value of the National Institutes of Health Stroke Scale(NIHSS)score and the Glasgow Coma Scale(GCS)score for bleeding in patients with acute cerebral infarction after thrombolytic therapy.Methods:A total of 281 patients with acute cerebral infarction were enrolled at Henan Provincial People's Hospital and were treated with urokinase or recombinant human tissue plasminogen activator(rt-PA)for thrombolysis.The patients were followed up for up to 1 month after thrombolysis.Data on age, sex, time to thrombolysis, smoking, systolic blood pressure, platelets, prothrombin time, international normalized ratio, and NIHSS and GCS scores were collected.Logistic regression analysis was used to identify related factors for bleeding after thrombolysis in acute cerebral infarction and the receiver-operating characteristic curve(ROC)was used to assess the predictive values of these factors through calculating the area under the curve(AUC).Results:Logistic regression analysis showed that time to thrombolysis, prothrombin time before thrombolysis, NIHSS score before thrombolysis, NIHSS score 24 h after thrombolysis, GCS score before thrombolysis, and GCS score 24 h after thrombolysis were independent factors for hemorrhage after thrombolytic therapy( OR=23.318, 0.238, 17.099, 4.561, 0.004, and 0.258, P=0.038, 0.021, 0.038, 0.027, 0.006, and 0.040, respectively).ROC curve analysis showed that NIHSS score before thrombolysis, NIHSS score 24 h after thrombolysis, and time to thrombolysis were important factors for predicting bleeding after thrombolysis(AUC=0.833, 0.795, and 0.714, respectively, all P=0.000). Conclusions:For patients with acute cerebral infarction, the risk of bleeding after thrombolysis is significantly increased if the NIHSS score is unfavorable before thrombolysis or 24 h after thrombolysis, or the duration of acute cerebral infarction is long.Attention to risk factors and early intervention are warranted.

13.
Acta Pharmaceutica Sinica B ; (6): 274-290, 2022.
Article in English | WPRIM | ID: wpr-929293

ABSTRACT

KRAS‒PDEδ interaction is revealed as a promising target for suppressing the function of mutant KRAS. The bottleneck in clinical development of PDEδ inhibitors is the poor antitumor activity of known chemotypes. Here, we identified novel spiro-cyclic PDEδ inhibitors with potent antitumor activity both in vitro and in vivo. In particular, compound 36l (K D = 127 ± 16 nmol/L) effectively bound to PDEδ and interfered with KRAS-PDEδ interaction. It influenced the distribution of KRAS in Mia PaCa-2 cells, downregulated the phosphorylation of t-ERK and t-AKT and promoted apoptosis of the cells. The novel inhibitor 36l exhibited significant in vivo antitumor potency in pancreatic cancer patient-derived xenograft (PDX) models. It represents a promising lead compound for investigating the druggability of KRAS‒PDEδ interaction.

14.
Article in Chinese | WPRIM | ID: wpr-928096

ABSTRACT

The immune checkpoint programmed cell death-ligand 1(PD-L1)-mediated immunosuppression is among the important features of tumor. PD-L1, an immunosuppressant, can induce T cell failure by binding to programmed cell death-1(PD-1). Thus, the key to restoring the function of T cells is inhibiting the expression of PD-L1. The Chinese medicinal Atractylodis Macrocephalae Rhizoma(AMR) has the anti-tumor, anti-inflammatory, antioxidant, and hypoglycemic activities, and the polysaccharide in AMR(PAMR) plays a crucial role in immunoregulation, but the influence on the immune checkpoints which are closely related to immunosuppression has not been reported. MicroRNA-34 a(miR-34 a) expression in esophageal carcinoma tissue is significantly lower than that in normal tissue. This study aims to investigate the inhibitory effect of PAMR on esophageal carcinoma cells, and the relationship between its inhibitory effect on PD-L1 expression and miR-34 a, which is expected to clarify the anti-tumor mechanism of PAMR. Firstly, different human esophageal carcinoma cell lines(EC9706, EC-1, TE-1, EC109 cells) were screend out, and expression of PD-L1 was determined. Then, EC109 cells, with high expression of PD-L1, were selected for further experiment. The result showed that PAMR suppressed EC109 cell growth. According to the real-time quantitative PCR(qPCR) and Western blot, it significantly suppressed the mRNA and protein expression of PD-L1, while promoting the expression of tumor suppressor miR-34 a. The confocal microscopy and luci-ferase assay proved that PAMR alleviated the inhibitory effect of PD-L1 while blocked miR-34 a. Additionally, the expression of PD-L1 was controlled by miR-34 a, and the combination of miR-34 a inhibitor with high-dose PAMR reversed the inhibitory effect of PAMR on PD-L1 protein expression. Thus, the PAMR may inhibit PD-L1 by increasing the expression of miR-34 a and regulating its downstream target genes. In conclusion, PAMR inhibits the expression of PD-L1 mainly by inducing miR-34 a.


Subject(s)
B7-H1 Antigen/pharmacology , Carcinoma , Cell Proliferation , Humans , MicroRNAs/metabolism , Polysaccharides/pharmacology
15.
Article in Chinese | WPRIM | ID: wpr-927925

ABSTRACT

This study was designed to explore the alleviating effect and mechanism of Glycyrrhizae Radix et Rhizoma against Psora-leae Fructus-induced liver injury based on network pharmacology and cell experiments. The active components of Glycyrrhizae Radix et Rhizoma and Psoraleae Fructus were first retrieved from the Encyclopedia of Traditional Chinese Medicine(ETCM), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Comparative Toxicogenomics Database(CTD), and literature and further screened by SwissADME. The obtained 25 potential toxic components of Psoraleae Fructus and 29 flavonoids in Glycyrrhizae Radix et Rhizoma were input into the SwissTargetPrediction for target predication. A total of 818 targets related to liver injury were screened out based on GeneCards and MalaCards, and 91 common targets of Psoraleae Fructus, Glycyrrhizae Radix et Rhizoma, and liver injury were obtained from Venny. STRING was applied for constructing the PPI network, and Metascape for analyzing the biological processes and signaling pathways that common targets participated in. Cytoscape was used to construct the component-target-disease network and component-target-pathway network for Glycyrrhizae Radix et Rhizoma against Psoraleae Fructus-induced liver injury. The predicted core targets were proto-oncogene tyrosine-protein kinase(SRC), phosphatidylinositol 4,5-bisphosphate 3-kinase subunit alpha(PIK3 CA), RAC-alpha serine/threonine-protein kinase(AKT1), etc, with PI3 K-AKT signaling pathway, MAPK signaling pathway, apoptosis, Toll-like receptor signaling pathway, and NF-κB signaling pathway mainly involved. Following the scree-ning of the main toxic and pharmacodynamic components, the pharmacodynamic effects were investigated by cell experiments. The results showed that licochalcone A was mainly responsible for alleviating coryfolin-induced liver injury, licochalcone B for coryfolin-and psoralidin-induced liver injury, and echinatin for corylifolinin-and bakuchiol-induced liver injury. The preliminary revealing of the alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury and the prediction of related mechanisms will provide reference for further mechanism research and reasonable clinical compatibility.


Subject(s)
Chemical and Drug Induced Liver Injury, Chronic , Drugs, Chinese Herbal/pharmacology , Glycyrrhiza , Humans , Medicine, Chinese Traditional , Network Pharmacology
16.
Article in Chinese | WPRIM | ID: wpr-927916

ABSTRACT

The present study explored the effect of co-amorphous technology in improving the dissolution rate and stability of silybin based on the puerarin-silybin co-amorphous system prepared by the spray-drying method. Solid-state characterization was carried out by powder X-ray diffraction(PXRD), polarizing microscopy(PLM), Fourier transform infrared spectroscopy(FT-IR), differential scanning calorimetry(DSC), etc. Saturated powder dissolution, intrinsic dissolution rate, moisture absorption, and stability were further investigated. The results showed that puerarin and silybin formed a co-amorphous system at a single glass transition temperature which was higher than that of any crude drug. The intrinsic dissolution rate and supersaturated powder dissolution of silybin in the co-amorphous system were higher than those of the crude drug and amorphous system. The co-amorphous system kept stable for as long as three months under the condition of 40 ℃, 75% relative humidity, which was longer than that of the single amorphous silybin. Therefore, the co-amorphous technology could significantly improve the dissolution and stability of silybin.


Subject(s)
Calorimetry, Differential Scanning , Desiccation , Drug Compounding/methods , Drug Stability , Silymarin , Solubility , Spectroscopy, Fourier Transform Infrared , Technology , X-Ray Diffraction
17.
China Pharmacy ; (12): 1430-1435, 2022.
Article in Chinese | WPRIM | ID: wpr-927188

ABSTRACT

OBJECTIVE To es tablish the fingerprints of pith-nodecayed and pith-decayed Scutellaria baicalensis ,and to investigate the difference of their anti-inflammatory activities. METHODS HPLC method was adopted to establish the fingerprints of 5 batches of pith-nodecayed S. baicalensis and 5 batches of pith-decayed S. baicalensis . SIMCA 14.1 software was adopted to screen the markers of weight difference between pith-decayed S. baicalensis and pith-nodecayed S. baicalensis ,using variable importance in projection (VIP)>1 as standard. Using the inhibitory rates of NO ,IL-6 and IL- 1β in supernatant of lipopo- lysaccharide(LPS)-induced monocyte macrophages (RAW264.7 cells)as indexes ,the anti-inflammatory activities of pith-decayed and pith-nodecayed S. baicalensis were evaluated and median effective concentration (EC50)of NO were calculated. The gray correlation method was used for spectrum-effect relationship analysis ;SPSS 26.0 software was used for cluster analysis using the inhibitory rates of NO ,IL-6 and IL- 1β in cells at the concentration of 50 μg/mL. RESULTS There were 15 common peaks in 5 batches of pith-nodecayed S. baicalensis and 5 batches of pith-decayed S. baicalensis ,and the similarity of them was greater than 0.990. There were total of 8 peaks with VIP 1.0,they were peak 14,12,15,6,10,13,11 and 4. At jcqinge@163.com the concentration of 50 μg/mL,the inhibitory rates of pith- decayed S. baicalensis extract to NO ,IL-6,IL-1 β and the average EC 50 were 62.14%-71.13%,3.32% -18.38% and 93.12%-95.47% and 25.35 μg/mL,respectively;those of pith-nodecayed S. baicalensis extract were 39.52%-50.19%, 6.21%-22.55%,94.10%-96.44% and 58.63 μg/mL,respectively. Average NO inhibition rate of pith-decayed S. baicalensis extract was significantly higher than that of pith- nodecayed S. baicalensis extract;average EC 50 and average IL- 6 inhibitory rate of pith-decayed S. baicalensis extract were significantly lower than those of pith-nodecayed S. baicalensis extract(P<0.05). There was no statistical significance in average inhibitory rate of IL- 1β(P>0.05). The correlation degrees of peaks 2-3,5-8 and 10-11 with inhibitory rate of NO were all greater than 0.8. The correlation degrees of peaks 2,5,8-9 with inhibitory rate of IL- 1β were all greater than 0.9. The correlation degrees of 15 common peaks with inhibitory rate of IL- 6 were all less than 0.8. Ten batches of samples could be grouped into two categories ,K1-K5 were clustered into one category and T 12-T16 were clustered into one category. CONCLUSIONS At the concentration of 50 µg/mL,the inhibitory effect of pith-decayed S. baicalensis extract to NO is stronger than that of pith-nodecayed S. baicalensis extract,while the inhibitory effect on IL- 6 is weaker than that of pith-nodecayed S. baicalensis extract;they have similar inhibitory effect on IL- 1β. The corresponding components of peak 6,10-11 are preliminarily identified as main chemical components of the difference in anti-inflammatory activity between pith-decayed S. baicalensis and pith-nodecayed S. baicalensis .

18.
Article in Chinese | WPRIM | ID: wpr-924167

ABSTRACT

ObjectiveTo determine the epidemiological characteristics and risk factors of a norovirus GII.17 outbreak in Minhang District of Shanghai in 2018, and provide evidence for prevention and control measures of norovirus infection. MethodsDescriptive epidemiological analysis was performed. In addition, a retrospective cohort study was conducted to determine the risk factors. ResultsFrom May 30th to June 1st of 2018, a total of 132 cases (126 clinical cases and 6 confirmed cases) were documented,with an attack rate of 29.20%(132/452).All cases were children in a kindergarten, with the average age of 5 years and 43.9% being male. The cases were reported in all the classes, with no clustering by class or floor.The epidemic curve was characterized by a point source exposure, which was estimated to be probably between 7 AM on May 30thand 0:30 AM on May 31st. The retrospective cohort study showed that the attack rate significantly differed between the children who had taken and did not take the school lunch (RR=∞) on May 30th,and those who had taken and did not take seafood noodles (RR=4.11, 95%CI:1.09-15.55) (P<0.05). Among a total of 73 specimens, six specimens collected in child cases and one specimen in an asymptomatic chef tested positive for GII.17 type of norovirus. In addition, one retained food specimen of seafood noodles was positive for Aeromonas hydrophila. Viral shedding in the asymptomatic chef remained over 30 days. ConclusionThe outbreak was caused by seafood noodles contaminated by norovirus. It warrants enhancement in the regulation of food safety in canteens and regular examination of norovirus infection in catering industry employees.

19.
Article in Chinese | WPRIM | ID: wpr-936096

ABSTRACT

Objective: The pattern of digestive tract reconstruction in radical gastrectomy for gastric cancer is still inconclusive. This study aims to compare mid-term and long-term quality of life after radical gastrectomy for distal gastric cancer between Billroth-I (B-I) and Billroth-II (B-II) reconstruction. Methods: A retrospective cohort study was conducted.Clinicopathological and follow-up data of 859 gastric cancer patients were colected cellected from the surgical case registry database of Gastrointestinal Surgery Center of Sichuan University West China Hospital, who underwent radical distal gastric cancer resection between January 2016 and December 2020. Inclusion criteria: (1) gastric cancer confirmed by preoperative gastroscopy and biopsy; (2) elective radical distal major gastrectomy performed according to the Japanese Society for Gastric Cancer treatment guidelines for gastric cancer; (3) TNM staging referenced to the American Cancer Society 8th edition criteria and exclusion of patients with stage IV by postoperative pathology; (4) combined organ resection only involving the gallbladder or appendix; (5) gastrointestinal tract reconstruction modality of B-I or B-II; (6) complete clinicopathological data; (7) survivor during the last follow-up period from December 15, 2021 to January 15, 2022. Exclusion criteria: (1) poor compliance to follow-up; (2) incomplete information on questionnaire evaluation; (3) survivors with tumors; (4) concurrent malignancies in other systems; (5) concurrent psychiatric and neurological disorders that seriously affected the objectivity of the questionnaire or interfered with patient's cognition. Telephone follow-up was conducted by a single investigator from December 2021 to January 2022, and the standardized questionnaire EORTC QLQ-C30 scale (symptom domains, functional domains and general health status) and EORTC QLQ-STO22 scale (5 symptoms of dysphagia, pain, reflux, restricted eating, anxiety; 4 single items of dry mouth, taste, body image, hair loss) were applied to evaluate postoperative quality of life. In 859 patients, 271 were females and 588 were males; the median age was 57.0 (49.5, 66.0) years. The included cases were divided into the postoperative follow-up first year group (202 cases), the second year group (236 cases), the third year group (148 cases), the fourth year group (129 cases) and the fifth year group (144 cases) according to the number of years of postoperative follow-up. Each group was then divided into B-I reconstruction group and B-II reconstruction group according to procedure of digestive tract reconstruction. Except for T-stage in the fourth year group, and age, tumor T-stage and tumor TNM-stage in the fifth year group, whose differences were statistically significant between the B-I and B-II reconstruction groups (all P<0.05), the differences between the B-I and B-II reconstruction groups in terms of demographics, body mass index (BMI), tumor TNM-stage and tumor pathological grading in postoperative follow-up each year group were not statistically significant (all P>0.05), suggesting that the baseline information between B-I reconstruction group and the B-II reconstruction group in postoperative each year group was comparable. Evaluation indicators of quality of life (EORTC QLQ-C30 and EORTC QLQ-STO22 scales) and nutrition-related laboratory tests (serum hemoglobin, albumin, total protein, triglycerides) between the B-I reconstruction group and B-II reconstruction group in each year group were compared. Non-normally distributed continuous variables were presented as median (Q(1),Q(3)), and compared by using the Wilcoxon rank sum test (paired=False). The χ(2) test or Fisher's exact test was used for comparison of categorical variables between groups. Results: There were no statistically significant differences in all indexes EORTC QLQ-30 scale between the B-I reconstruction group and the B-II reconstruction group among all postoperative follow-up year groups (all P>0.05). The EORTC QLQ-STO22 scale showed that significant differences in pain and eating scores between the B-I reconstruction group and the B-II reconstruction group were found in the second year group, and significant differences in eating, body and hair loss scores between the B-I reconstruction group and the B-II reconstruction group were found in the third year group (all P<0.05), while no significant differences of other item scores between the B-I reconstruction group and the B-II reconstruction group were found in postoperative follow-up of all year groups (P>0.05). Triglyceride level was higher in the B-II reconstruction group than that in the B-I reconstruction group (W=2 060.5, P=0.038), and the proportion of patients with hyperlipidemia (triglycerides >1.85 mmol/L) was also higher in the B-II reconstruction group (19/168, 11.3%) than that in the B-I reconstruction group (0/34) (χ(2)=0.047, P=0.030) in the first year group with significant difference. Albumin level was lower in the B-II reconstruction group than that in the B-I reconstruction group (W=482.5, P=0.036), and the proportion of patients with hypoproteinemia (albumin <40 g/L) was also higher in the B-II reconstruction group (19/125, 15.2%) than that in the B-I reconstruction group (0/19) in the fifth year group, but the difference was not statistically significant (χ(2)=0.341, P=0.164). Other nutrition-related clinical laboratory tests were not statistically different between the B-I reconstruction and the B-II reconstruction in each year group (all P>0.05). Conclusions: The effects of both B-I and B-II reconstruction methods on postoperative mid-term and long-term quality of life are comparable. The choice of reconstruction method after radical resection of distal gastric cancer can be based on a combination of patients' condition, sugenos' eoperience and operational convenience.


Subject(s)
Aged , Albumins , Alopecia/surgery , Female , Gastrectomy/methods , Gastric Bypass , Humans , Male , Middle Aged , Pain , Quality of Life , Registries , Retrospective Studies , Stomach Neoplasms/surgery , Treatment Outcome , Triglycerides
20.
Article in Chinese | WPRIM | ID: wpr-928885

ABSTRACT

With the advent of the era of artificial intelligence, as an emerging technology, radiomics can extract a large amount of quantitative information describing the physiological condition and phenotypic characteristics of tumors with high throughput from the massive data of CT, MRI and other imaging tomography, and analyze these high-dimensional imaging omics features containing disease pathophysiological information can be used to accurately determine tumor differentiation, staging, and predict tumor behavior, which has broad application prospects. This article aims to introduce the technical principles of radiomics and its abdominal tumor application status, and to prospect its application prospects in pediatric abdominal neuroblastoma.


Subject(s)
Abdominal Neoplasms/diagnostic imaging , Artificial Intelligence , Child , Humans , Magnetic Resonance Imaging , Precision Medicine , Tomography, X-Ray Computed
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