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1.
Acta Pharmaceutica Sinica ; (12): 178-187, 2022.
Article in Chinese | WPRIM | ID: wpr-913162

ABSTRACT

Blocking immune checkpoint programmed cell death receptor 1 (PD-1) or programmed death receptor-ligand 1 (PD-L1) can enhance anti-tumor activity of effector T cells. However, the lack of response in many patients to PD-1/PD-L1 therapy remains a question. Improving the immunosuppressive tumor microenvironment (TME) to enhance the efficacy of immune checkpoint inhibitors has become a promising cancer treatment strategy. We constructed a liposome system (PD-L1/siCXCL12-Lp) of CXCL12 siRNA and anti-PD-L1 peptide with matrix metalloproteinases (MMPs) responsiveness, which combined the TME regulation of siCXCL12 and the immune regulation of anti-PD-L1 peptide. All animal experiments were approved by the Biomedical Ethics Committee of Peking University. The authors found that PD-L1/siCXCL12-Lp directly down-regulated the expression of CXCL12 in vitro (33.8%) and in vivo (15.5%). It also effectively increased the ratio of CD8+/Treg by 20.0%, which helped the anti-PD-L1 peptide to better exert its immune effect. The combination therapy significantly inhibited tumor growth (52.08%) with great safety, which explored a new idea for cancer immunotherapy.

2.
Protein & Cell ; (12): 557-577, 2021.
Article in English | WPRIM | ID: wpr-888707

ABSTRACT

Additional sex combs-like 1 (ASXL1) interacts with BRCA1-associated protein 1 (BAP1) deubiquitinase to oppose the polycomb repressive complex 1 (PRC1)-mediated histone H2A ubiquitylation. Germline BAP1 mutations are found in a spectrum of human malignancies, while ASXL1 mutations recurrently occur in myeloid neoplasm and are associated with poor prognosis. Nearly all ASXL1 mutations are heterozygous frameshift or nonsense mutations in the middle or to a less extent the C-terminal region, resulting in the production of C-terminally truncated mutant ASXL1 proteins. How ASXL1 regulates specific target genes and how the C-terminal truncation of ASXL1 promotes leukemogenesis are unclear. Here, we report that ASXL1 interacts with forkhead transcription factors FOXK1 and FOXK2 to regulate a subset of FOXK1/K2 target genes. We show that the C-terminally truncated mutant ASXL1 proteins are expressed at much higher levels than the wild-type protein in ASXL1 heterozygous leukemia cells, and lose the ability to interact with FOXK1/K2. Specific deletion of the mutant allele eliminates the expression of C-terminally truncated ASXL1 and increases the association of wild-type ASXL1 with BAP1, thereby restoring the expression of BAP1-ASXL1-FOXK1/K2 target genes, particularly those involved in glucose metabolism, oxygen sensing, and JAK-STAT3 signaling pathways. In addition to FOXK1/K2, we also identify other DNA-binding transcription regulators including transcription factors (TFs) which interact with wild-type ASXL1, but not C-terminally truncated mutant. Our results suggest that ASXL1 mutations result in neomorphic alleles that contribute to leukemogenesis at least in part through dominantly inhibiting the wild-type ASXL1 from interacting with BAP1 and thereby impairing the function of ASXL1-BAP1-TF in regulating target genes and leukemia cell growth.

3.
Chinese Medical Journal ; (24): 1584-1592, 2021.
Article in English | WPRIM | ID: wpr-887592

ABSTRACT

BACKGROUND@#There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China.@*METHODS@#From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n  = 72) or allo-HSCT (n  = 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups.@*RESULTS@#Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P = 0.001), chemotherapy-resistant disease (41% vs. 8%, P = 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2-143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300).@*CONCLUSIONS@#Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.


Subject(s)
China , Hematopoietic Stem Cell Transplantation , Humans , Lymphoma, T-Cell, Peripheral/therapy , Neoplasm Recurrence, Local , Retrospective Studies , Transplantation, Autologous , Transplantation, Homologous , Treatment Outcome
4.
Article in Chinese | WPRIM | ID: wpr-885115

ABSTRACT

Objective:To investigate the relationship between serum lipocalin-2 level and the risk of cardiovascular disease(CVD) in patients with type 2 diabetes.Methods:A total of 279 type 2 diabetic patients were enrolled in this study. Basic information and clinical data were collected. These patients were divided into CVD group and non-CVD group according to their cardiovascular disease status. Serum lipocalin-2 level was assessed by enzyme linked immunosorbent assay.Results:Compared to non-CVD group, serum lipocalin-2 level was significantly higher in CVD group( P<0.01). The Spearman correlation analysis showed that serum lipocalin-2 level was positively correlated with waist circumstance, diastolic blood pressure, uric acid, triglyceride, and HbA 1C( P<0.05), while negatively correlated with high density lipoprotein-cholesterol level( P<0.01). In addition, the univariate and multivariate logistic regression analysis revealed that serum lipocalin-2 was an independent risk factor for CVD( P<0.01)after adjustment for potential confounders. Moreover, receiver operating characteristic curve analysis demonstrated that the area under curve value of lipocalin-2 was 0.74, with the optimal cutoff value of lipocalin-2 66.84 ng/mL. Conclusion:Serum lipocalin-2 is closely associated with CVD in patients with type 2 diabetes, which might be considered as one of the predictors for CVD in type 2 diabetes mellitus.

5.
Chinese Journal of Urology ; (12): 89-96, 2021.
Article in Chinese | WPRIM | ID: wpr-884965

ABSTRACT

Objective:To study and compare the prognosis of different pathological subtypes of renal cell carcinoma (RCC).Methods:Clinicopathological and prognostic data of 1 346 cases of postoperative renal cell carcinoma during July 2002 to June 2014 in West China Hospital were collected retrospectively.There were 839 males and 507 females, aged (55.1±13.4)years, including 1 120 cases of clear cell RCC, 62 cases of papillary RCC, 79 cases of chromophobe RCC and 85 cases of the other pathological types respectively. ECOG 0 and ≥1 were 911 and 435 cases, with; T 1, T 2, T 3 and T 4 of 1 019, 177, 102 and 48 cases respectively; WHO nuclear grade for well, intermediate, poor differentiation and unknown were 587, 530, 85 and 144 cases separately.Tumor size <5cm, 5-10cm, ≥10cm and unknown were 685, 541, 104 and 16 cases.Combined with necrosis or sacromatoid differentiation were 200/1 146 and 27/1 319 cases separately. Meanwhile, data of 80 439 cases from Surveillance, Epidemiology, and End Results Program (SEER) were also collected.There were 51 371 males and 29 068 females, aged (60.9±12.4) years; , with 66 261, 8 680, 5 022 and 476 cases of White, Black, Asian, American native, or unknown race separately. There were 62 600 of clear cell RCC, 12 170 of papillary RCC, 4 354 of chromophobe RCC and 1 315 of other pathological types, with T 1, T 2, T 3 and T 4 of 55 332, 8 687, 15 516 and 904 cases respectively; WHO nuclear grade for well, intermediate and poor differentiation were 52 323, 22 700 and 5 416 cases separately.Tumor size <5cm, 5-10cm, ≥10cm were 46 741, 25 760 and 7 938 cases respectively. Kaplan-Meier survival analysis were performed on these two group of cases, with different factors between subgroups (gender, age, pathological types, tumor stage, size and nuclear grade) evaluated by log-rank test. To evaluate accuracy of outcome prediction models of SSIGN, Leibovich and UISS score, concordance index of these models were evaluated. Results:In 1 346 cases of our cohort, those with chromophobe RCC were well prognostic, survival were relatively better in clear cell RCC than that of papillary RCC, and worst prognosis were demonstrated in those with other types of RCC (5 year overall survival rate: 97.5%, 87.9%, 79.7% and 68.4% separately). Poor prognosis were seen in those older than 50 years, with poor T stage or nuclear grade, large tumor size and tumors with necrosis or sacromatoid differentiation ( P<0.05). In 80 439 seer cases, the best prognosis was also seen in chromophobe RCC and the worst in other type of RCC separately (5 year overall survival rate: 96.3% and 85.3%). In addition, longer survival was seen in papillary RCC than clear cell RCC (5 year overall survival rate: 92.5% and 88.9%). However, similar results with our cohort were seen in Asian and American native subgroup of SEER cases (95.1%, 88.6%, 86.7%, 80.2% for chromophobe, clear cell, papillary and other types of RCC respectively). Poor prognosis were seen in those older than 50 years, males, Asian/ American Indian, poor T stage or nuclear grade and large tumor size ( P<0.05). Concordance index for SSIGN, Leibovich and UISS models in our cohort were 0.763-0.781, 0.725-0.752 and 0.641-0.660, respectively. The chromophobe RCC subgroup was relative better based on predictive value of prognosis models(c-index of UISS of 0.670-0.781, SSIGN and Leibovich of 0.733-0.903). Conclusions:In Asian RCC population, prognosis of chromophobe RCC is best, clear cell RCC is slightly better than papillary RCC, and the prognosis of other types of RCC is the worst. Concordance index of SSIGN and Leibovich in our cohort were higher than that of UISS, and the use value for predictive model was better in the chromophobe RCC subgroup.

6.
Chinese Journal of Orthopaedics ; (12): 386-397, 2021.
Article in Chinese | WPRIM | ID: wpr-884723

ABSTRACT

Due to good mechanical properties and biocompatibility, tissue engineering scaffolds have become the vital method for repairing and regenerating articular cartilage defects. With the continuous development of tissue engineering technology, many scaffolds preparation and formation methods have been developed and tested in the past decade, however, the preparation of ideal regenerative scaffolds remain controversial. As load-bearing tissue inside the body joints, the matrix structure and cell composition of articular cartilage are hierarchical, and there are several smooth natural gradients from the cartilage surface to the subchondral bone layer, including cell phenotype and number, specific growth factors, matrix composition, fiber arrangement, mechanical properties, nutrient and oxygen consumption. Therefore, in the design of regenerative scaffolds, it is necessary to achieve these gradients to regenerate articular cartilage in situ. In recent studies, many new biomimetic gradient scaffolds have been used to simulate the natural gradient of articular cartilage. These scaffolds show different mechanical, physicochemical or biological gradients in the structure, and have achieved good repair effects. The related articles on tissue engineering for the treatment of articular cartilage defects were retrieved by searching databases with key wordsarticular cartilage injury, cartilage repair and gradient scaffolds. In this work,the structural, biochemical, biomechanical and nutrient metabolism gradients of natural articular cartilage were studied and summarized firstly. Then, the latest design and construction of articular cartilage gradient scaffolds were classified. Besides that, the material composition (such as hydrogels, nanomaterials, etc.) and the preparation process (such as electrospinning, 3D printing, etc.) of grandient scaffolds were further enhanced. Finally, the prospect and challenge of biomimetic gradient scaffolds in cartilage engineering are discussed, which provides a theoretical basis for the successful application of gradient scaffolds in clinical transformation.

7.
Article in Chinese | WPRIM | ID: wpr-884623

ABSTRACT

Objective:To study the clinical features of the "migration birds" population in Hainan Province in winter presenting with acute cholecystitis.Methods:Patients who were diagnosed to suffer from acute cholecystitis in the winter months from November to February of the following year of 2017, 2018 and 2019 and admitted in Hainan Hospital of Chinese PLA General Hospital were included in this study. The "migration birds" patients who arrived in Hainan Province in less than 30 days were defined as the short-term group ( n=49), 30-89 days as the mid-term group ( n=24), more than 90 days as the long-term group ( n=48). The general information, associated medical diseases, clinical presentations, interventional strategies and in-hospital outcomes were compared, and further analyze the clinical characteristics of patients with purulent cholecystitis and non-purulent cholecystitis in the short-term group. Results:Of 120 patients, there were 49 patients in the short-term group (29 males and 20 females with an average age of 65.18±15.02 years), 24 patients in the mid-term group (13 males and 11 females with an average age of 66.21±11.93 years), and 48 patients in the long-term group (30 males and 18 females with an average of 60.73±12.54 years). The general information, interventional strategies and in-hospital outcomes were similar among the three groups. When compared with patients in the long-term group, patients in the short-term group had higher incidences of hypertension [20.83% (10/48) vs 48.98% (24/49)] and diabetes [10.42% (5/48) vs 30.61% (15/49)]. The gallbladder wall in the short-term group was significantly thicker than that in the long-term group [0.60(0.40, 0.70) cm vs 0.50(0.30, 0.60) cm, P<0.017]. The proportion of purulent cholecystitis in the short-term group was significantly higher than that in the long-term group [48.15% (13/27) vs 17.24% (5/29) , P<0.017] . In the short-term group, the incidences of silt-like stones of purulent cholecystitis [38.46% (5/13) vs 14.29% (2/14)], gallbladder perforation [30.77% (4/13) vs 0], gallbladder gangrene [53.85% (7/13) vs 7.14% (1/14)], perigallbladder effusion [76.92% (10/13) vs 14.29% (2/14)], abdominal effusion [46.15% (6/13) vs 7.14% (1/14)] were significantly higher than that of patients with non-purulent cholecystitis, (all P<0.05). Conclusion:Patients presenting with acute cholecystitis after arrival in Hainan in the short term had more severe inflammation with complications of suppuration, perforation and gangrene. Patients with hypertension and diabetes were the high risk group of patients presenting with acute cholecystitis after short-term arrival in Hainan.

8.
Chinese Journal of Endemiology ; (12): 399-403, 2021.
Article in Chinese | WPRIM | ID: wpr-883734

ABSTRACT

Objective:To explore the correlation between fluoride intake and serum alkaline phosphatase (ALP) in pregnant women of different gestational periods in endemic fluorosis area.Methods:Pregnant women in Rencheng District, Jinxiang County, Jiaxiang County of Jining City and Yuncheng County of Heze City were selected in April 2020. According to the gestational weeks, pregnant women were divided into early pregnancy group (0 - 12 weeks), middle pregnancy group (13 - 27 weeks) and late pregnancy group (> 27 weeks). The levels of urinary fluoride, ALP, osteocalcin (BGP), C-terminal peptide of β-Ⅰ collagen (β-CTX) and N-terminal propeptide of type Ⅰ collagen (PINP) of pregnant women in each group were measured, and the correlation between urinary fluoride and ALP, BGP, β-CTX, and PINP in pregnant women of different gestational periods was analyzed.Results:A total of 372 pregnant women were selected, including 97 cases in early pregnancy group, 169 cases in middle pregnancy group and 106 cases in late pregnancy group. There was no significant difference in urinary fluoride level between the three groups [(1.20 ± 0.25), (1.23 ± 0.19), (1.24 ± 0.30) mg/L, P > 0.05]. There was significant difference in serum ALP among the three groups ( P < 0.05), among them, the ALP level in early pregnancy was significantly lower than those of middle pregnancy group and late pregnancy group ( P < 0.05), and the ALP level in middle pregnancy was significantly lower than that of late pregnancy group ( P < 0.05). There was no significant differences in serum β-CTX among the three groups ( P > 0.05). There were significant differences in serum BGP and PINP levels among the three groups ( P < 0.05). The serum BGP and PINP levels in late pregnancy group were significantly higher than those of early pregnancy group and middle pregnancy group ( P < 0.05), and there were no significant differences in serum BGP and PINP levels between early pregnancy group and middle pregnancy group ( P < 0.05). There was a significant positive correlation between urinary fluoride and ALP in early pregnancy group ( r = 0.364, P < 0.05), but no significant correlation between urinary fluoride and BGP, β-CTX and PINP ( r = 0.164, 0.117, 0.136, P > 0.05). There was a significant positive correlation between urinary fluoride level and ALP in middle pregnancy group ( r = 0.417, P < 0.05), but no significant correlation between urinary fluoride level and BGP, β-CTX and PINP ( r = 0.127, 0.108, 0.129, P > 0.05). There was no significant correlation between urinary fluoride level and ALP, BGP, β-CTX and PINP in late pregnancy group ( r = 0.179, 0.158, 0.184, 0.149, P > 0.05). Conclusions:The urinary fluoride level of pregnant women in endemic fluorosis area is relatively stable in gestational period. The urinary fluoride level affects the ALP secretion of pregnant women in early and middle pregnancy. It is still necessary to strengthen the measures of improving water quality and defluoridation to reduce the impact of excessive fluoride intake on pregnancy complications in endemic fluorosis area.

9.
Article in Chinese | WPRIM | ID: wpr-883026

ABSTRACT

Objective:To explore the application effect of optimizing diet management in patients with hyperphosphatemia.Methods:Seventy-seven patients who underwent regular hemodialysis in the blood purification department of the First Affiliated Hospital of Guangxi Medical University from September 2018 to June 2019 were selected. Patients were randomly divided into control group (39 cases) and intervention group (38 cases) by the method of random number table. The control group received routine nursing, while the intervention group received optimized dietary management intervention. The blood phosphorus, blood calcium, hemoglobin, albumin, dietary phosphorus related knowledge level and phosphorus control diet compliance of the two groups before and after the intervention were compared respectively.Results:After 3 months of intervention, the scores of knowledge about food phosphorus, compliance of phosphorus control diet and total score of the intervention group were (22.00±3.92), (34.82±4.69) and (56.82±7.48) points, which were higher than (18.46±3.57), (30.54±3.52) and (49.00±6.13) points of the control group, the difference was statistically significant ( tvalues were 4.146, 4.536 and 5.022, P<0.05). After 6 months of intervention, the scores of knowledge about food phosphorus, compliance of phosphorus control diet and total score of the intervention group were (25.74±3.36), (41.63±5.27) and (67.37±7.67) points, which were higher than (20.97±3.81), (32.36±4.38) and (53.33±6.80) points of the control group, the difference was statistically significant ( tvalues were 5.815, 8.403 and 8.504, P<0.05). After 3 months of intervention, the blood phosphorus level in the intervention group was 1.81 (1.67, 2.10) mmol/L, which was lower than 2.13 (1.87, 2.32) mmol/L in the control group, the difference was statistically significant ( Zvalue was-3.237, P<0.05). After 6 months of intervention, the blood phosphorus level in the intervention group was 1.75 (1.63, 1.91) mmol/L, which was lower than that in the control group 1.90 (1.83, 2.13) mmol/L, and the difference was statistically significant ( Zvalue was-3.343, P<0.01). Conclusion:Optimizing dietary management can improve patients' knowledge level of food phosphorus and dietary compliance of phosphorus control, effectively reduce blood phosphorus level, and have no obvious effect on nutritional status.

10.
Article in Chinese | WPRIM | ID: wpr-880065

ABSTRACT

OBJECTIVE@#To analyze the characteristics, prognosis and risk factors of bloodstream infection in patients with hematological malignancies in the tropics, so as to provide evidence for the prevention and treatment of bloodstream infection.@*METHODS@#The clinical features, blood culture results and prognosis of patients with bloodstream infection in patients with hematological malignancies admitted to Hainan Hospital of PLA General Hospital were retrospectively studied.@*RESULTS@#The most common primary infection site of the 81 patients with hematological malignancies was lung (46.91%), followed by PICC (11.11%). The detection rate of Gram-positive bacteria and Gram-negative bacteria in the blood culture was 60.98% and 30.02%, respectively. Coagulase-negative staphylococci was the most common Gram-positive bacteria resulting in bloodstream infection in our study. Of the Gram-negatives, Klebsiella pneumoniae (34.38%) was predominant, followed by Escherichia coli (18.75%) and Pseudomonas aeruginosa (18.75%). Gram-positive bacteria was highly sensitive (100%) to vancomycin, linezolid and tigecycline. Study showed that Gram-negative bacteria had low sensitive to quinolones, in particular, the resistance rate of Escherichia coli to quinolones was as high as 83.33%. In terms of overall survival (OS), the 30-days OS of patients with Gram-negative and Gram-positive septicemia was 77.42% and 92.00%, respectively. There was no statistically significant difference between the two groups. Multivariate analysis revealed that septic shock (P=0.001, RR=269.27) was an independent risk factor for 30-day mortality, and remission status (P=0.027, RR=0.114) was an independent predictor of a favourable outcome of bloodstream infection in patients with hematological malignancies.@*CONCLUSION@#Gram-positive bacteria are the main pathogens causing bloodstream infections in patients with hematological malignancies in the tropics. Improving the care of PICC is an important measure to reduce the incidence of bloodstream infection in patients with hematological malignancies in the tropics. A correct treatment relieving disease and effective prevention and treatment of septic shock can reduce mortality of patients with bloodstream infection in patients with hematological malignancies in the tropics.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Drug Resistance, Bacterial , Gram-Negative Bacteria , Hematologic Neoplasms/drug therapy , Humans , Microbial Sensitivity Tests , Prognosis , Retrospective Studies , Sepsis
11.
Acta Pharmaceutica Sinica B ; (6): 3244-3261, 2021.
Article in English | WPRIM | ID: wpr-922791

ABSTRACT

Major challenges for cancer treatment are how to effectively eliminate primary tumor and sufficiently induce immunogenic cell death (ICD) to provoke a robust immune response for metastasis control. Here, a self-assembled cascade bioreactor was developed to improve cancer treatment with enhanced tumor penetration and synergistic therapy of starvation, chemodynamic (CDT) and photothermal therapy. Ultrasmall FeS-GOx nanodots were synthesized with glucose oxidase (GOx) as template and induced by paclitaxel (PTX) to form self-assembling FeS-GOx@PTX (FGP)

12.
Article in Chinese | WPRIM | ID: wpr-907401

ABSTRACT

Objective:To explore the role of casein kinase 1 gamma 2 (CSNK1G2) in the development and progression of head and neck squamous cell carcinoma (HNSC).Methods:Based on the Cancer Genome Atlas (TCGA), LinkedOmics and UALCAN were used to analyze the relationship among the mRNA expression of CSNK1G2, methylation, copy number variation and clinical indicators in HNSC, as well as to analysis CSNK1G2 related co-expression genes and proteins. The expression of CSNK1G2 in HNSC was verified by RT-qPCR experiments of clinical samples. Protein interaction network analysis on CSNK1G2 expression-related proteins was performed using STRING database.Results:UALCAN analysis showed that the expression of CSNK1G2 mRNA in HNSC was higher than that in normal tissues ( P<0.001), and the expression of CSNK1G2 mRNA was up-regulated in lower differentiation and Human Papilloma Virus (HPV)-positive HNSC (all P<0.05). But in HNSC with different pathological stages, different age stages and different lymph node metastasis stages (N stage), there was no difference in the amount of CSNK1G2 mRNA expression (all P>0.05). The RT-qPCR experiment confirmed the increased expression of CSNK1G2 mRNA in HNSC. LinkedOmincs analysis results showed that CSNK1G2 mRNA expression was positively correlated with CSNK1G2 copy number variation ( P<0.001) and negatively correlated with methylation ( P<0.001). Survival analysis results showed that high CSNK1G2 mRNA expression and copy number mutations predicted better survival ( P=0.033, P=0.015), while methylation levels were not associated with survival ( P=0.458). Gene set enrichment analysis results showed that CSNK1G2-related co-expression genes were mainly in DNA replication. The STRING's protein interaction network analysis results showed that TP53, CHEK1, and CHEK2 may be key proteins. These proteins are significantly associated with high expression levels of CSNK1G2. Conclusions:CSNK1G2 may cooperate with TP53, CHEK1 and CHEK2 related proteins to promote the development of HNSC and tumor proliferation, but does not affect the metastasis and spread of HNSC. An increase in the expression of CSNK1G2 in HNSC may indicate a better survival prognosis.

13.
Article in Chinese | WPRIM | ID: wpr-906511

ABSTRACT

Objective:To observe the effect of Zuoguiwan on bone metabolism and Wnt/<italic>β</italic>-catenin signaling pathway in ovariectomized osteoporotic rats model, and to explore the molecular biological mechanism of Zuoguiwan in the prevention and treatment of osteoporosis. Method:The rat model of postmenopausal osteoporosis was established by bilateral ovariectomy, 60 female SD rats were randomly divided into sham operation group, model group, positive group (estradiol valerate tablet 0.05 mg·kg<sup>-1</sup>·d<sup>-1</sup>) and low, middle and high dose groups of Zuoguiwan (5.5,11,22 g·kg<sup>-1</sup>·d<sup>-1</sup>).After successful establishment of the model in the 13<sup>th</sup> week, intragastric administration (<italic>ig</italic>) was given once a day for a total of 12 weeks. After administration, the histomorphological changes of femur in rats were observed by hematoxylin-eosin (HE) staining, the bone mineral density (BMD) and bone mineral content(BMC) of femur were measured by dual energy X-ray apparatus, and the biomechanical properties of bone were measured by MTS Acumen3 biomechanical testing system. The contents of bone alkaline phosphatase (BALP), bone glaprotein(BGP),estradiol (E<sub>2</sub>) ,and tartrate-resistant acid phosphatase (TRAP), type Ⅰ procollagen N-terminal propeptide (PINP) in serum were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the protein level of Wnt2,<italic>β</italic>-catenin,low density lipoprotein related receptor protein 5 (LRP5) and the phosphorylation level of glycogen synthase kinase-3<italic>β</italic>(GSK-3<italic>β</italic>) in rat tibia. Result:Compared with sham operation group, the maximum load and stiffness of BMD,BMC, in the model group decreased significantly(<italic>P</italic><0.01), the contents of E<sub>2</sub> and PINP in serum decreased significantly(<italic>P</italic><0.01), the content of BALP,BGP,TRAP increased significantly(<italic>P</italic><0.01), the expression levels of Wnt2,p-GSK-3<italic>β </italic>Ser9,LRP5 and <italic>β</italic>-catenin protein in bone tissue decreased significantly(<italic>P</italic><0.01), the trabecula of femur became thinner and thinner, the number of bone trabeculae decreased. Compared with model group, the maximum load and stiffness of BMD,BMC, in estradiol group and Zuoguiwan group were significantly increased (<italic>P</italic><0.05,<italic>P</italic><0.01), the contents of serum E<sub>2</sub> and PINP were significantly increased (<italic>P</italic><0.05,<italic>P</italic><0.01), the content of BALP,BGP,TRAP was significantly decreased (<italic>P</italic><0.01), and the expression level of Wnt2,p-GSK-3<italic>β</italic> Ser9,LRP5, <italic>β</italic>-catenin protein in bone tissue was significantly increased (<italic>P</italic><0.05,<italic>P</italic><0.01) , the trabeculae of femur became thicker, the number increased, the structure was basically clear. Conclusion:Zuoguiwan has a certain preventive and therapeutic effect on osteoporosis in ovariectomized rats, and its mechanism may be related to increasing the level of estrogen, activating Wnt/<italic>β</italic>-catenin signaling pathway, up-regulating the expression of Wnt2 and LRP5 protein, inhibiting the activity of GSK-3<italic>β</italic>, reducing the degradation of <italic>β</italic>-catenin, coordinating the dynamic coupling balance between bone formation and bone resorption, correcting the disorder of bone metabolism and improving bone morphology.

14.
Article in Chinese | WPRIM | ID: wpr-875951

ABSTRACT

Objective A SYBR-Green real-time quantitative PCR(RT-qPCR)method was set up to detect the infection and proliferation of measles virus, which could be useful in virus titer determination. Methods In this project, we used a 405 bp fragment of the N gene of measles virus as a target sequence and constructed a plasmid to establish the standard curve in absolute quantitative experiment. We then used this method to obtain the proliferation curve of measles virus and to detect the virus proliferation at different MOI. Results There was a linear relationship between the virus copy number and the titer of the measles virus reference at the range of 6 to 2 lgCCID50/mL, with a correlation coefficient (r) of 0.991(P < 0.01). Based on the analysis of virus proliferation curve, measles virus mainly proliferated intracellularly within 48 h after its entering the cell. There was no detected increase in viral RNA level in the first 24 h, suggesting the virus was in a silent period in the cell. After 24 h, the virus expanded in large numbers and entered the exponential growth phase. The intracellular viral RNA level reached the plateau phase after its peak at 96 h. The virus secreted to the outside of the cell entered the exponential growth phase starting from 48 h, peaked at 144 h, then followed by plateau phase. Conclusion A SYBR-Green RT-qPCR method is established and used to monitor virus proliferation. Our result is helpful in understanding of the proliferation and secretion of measles virus in cells and provides experimental basis for detection of live attenuated virus titers.

15.
Chinese Journal of Neurology ; (12): 1273-1281, 2021.
Article in Chinese | WPRIM | ID: wpr-911866

ABSTRACT

Objective:To explore the relationship between seizure cluster of temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) and cortisol (COR) rhythm, and understand its mechanism from the perspective of neuroendocrine.Methods:Fifty-seven patients with unilateral TLE-HS were recruited from the Qinghai Provincial People′s Hospital from May 1st 2012 to December 31st 2020. According to the history of seizure clusters one month before admission, 27 patients were enrolled in seizure clusters group (SC group), 30 patients were included in without seizures cluster group (NSC group). The clinical characteristics were systematically analyzed and compared between the SC and NSC groups. Plasma COR levels were measured at 8:00, 16:00 and 24:00 (COR8, COR16 and COR0) on the same day, and bilateral magnetic resonance spectroscopy (MRS) diagnosis was performed in two groups. Independent sample t test, chi-square test, repeated analysis of variance, covariance analysis, and multivariate Logistic regression were used for statistical analysis. Results:Time effect, grouping effect and the interaction effect of the time and grouping in the level of COR were statistically significant. Covariance analysis excluded age as an influential factor, COR16, COR0 and the slope of COR8-16 in the SC group [(126.22±19.98) μg/L, (51.63±21.43) μg/L, -7.78±4.54] were higher than the NSC group [(97.70±18.55) μg/L, (31.90±10.73) μg/L, -12.40±4.16], and the difference was statistically significant ( F=5.587, 4.320, 4.013, all P<0.05). The slope of COR0-8 in the SC group (17.11±6.32) was lower than that in the NSC group (20.62±6.54), and the difference was statistically significant ( F=-2.065, P<0.05). There was no significant difference in lateralization of hippocampal sclerosis between the two groups, and there was no significant difference in the ratio of N-acetyl aspartic acid(NAA)/[choline(Cho)+creatinine(Cr)] in the unilateral hippocampal sclerosis zone of the two groups, but the NAA/(Cho±Cr) ratio of the contralateral hippocampus in the SC group (0.71±0.03) was lower than that in the NSC group (0.76±0.06),and the difference was statistically significant ( t=4.999, P=0.029). Multivariate Logistic regression analysis showed that COR16 ( OR=1.328, 95% CI 1.073-1.642, P=0.009), COR8-16 ( OR=3.657, 95% CI 1.404-9.525, P=0.008) were independent risk factors of seizure clusters in TLE-HS. Conclusion:COR rhythm disturbance may be the neuroendocrine basis of seizure clusters in patients with TLE-HS.

16.
Article in Chinese | WPRIM | ID: wpr-911684

ABSTRACT

Objective:To evaluate the effectiveness and safety of enhanced recovery after surgery(ERAS)in perioperative period of liver transplantation.Methods:The authors searched systematically domestic and foreign databases to collect researches on applying ERAS for liver transplantation. The retrieval period was from database inception to November 2020. Quality assessment and data extraction were performed by two researchers according to the inclusion criteria. Meta-analysis of postoperative indicators(length of ICU stay, total length of hospital stay, postoperative complications, admission rate & mortality rate)was performed by RevMan 5.3.5 software.Results:3 Three randomized controlled studies (RCTs) and 4 cohort studies were selected with a total of 1 016 patients, including 404 in ERAS group and 612 in conventional group(traditional perioperative management). The results of Meta-analysis revealed that, as compared with control group, length of ICU stay was significantly shorter in ERAS group [weighted mean difference(WMD)=-2.20, 95% CI: -2.43~-1.97, P<0.05]; Total length of hospital stay was significantly shorter in ERAS group [WMD=-5.85, 95% CI: -8.20~-3.49, P<0.05]; The incidence of postoperative complications was significantly shorter in ERAS group [OR=0.61, 95% CI: 0.42~0.88, P<0.05]. However, no inter-group statistically significant differences existed between admission rate or mortality rate( P>0.05). Conclusions:In perioperative period of liver transplantation, using ERAS protocol can shorten length of ICU stay and total length of hospital stay, lower the incidence of postoperative complications and accelerate patient recovery.

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Article in Chinese | WPRIM | ID: wpr-909016

ABSTRACT

Teaching rounds are an important part of hospitals at all levels to carry out clinical teaching work and improve medical quality. Taken anesthesia-related knowledge as the center, based on the patient's pathophysiology and anesthesia physiological changes, our department asked the core questions such as the impact of the operation method and anesthesia plan, then students answered, and finally closed the loop after the case. This process is called problem-based learning (PBL) teaching rounds. It is found that the teaching rounds can help improve the ability of anesthesiologists to solve problems, learn independently, and learn throughout their lives, thereby improving the teaching quality of standardized residency training of anesthesiology.

18.
China Pharmacy ; (12): 2219-2223, 2020.
Article in Chinese | WPRIM | ID: wpr-825651

ABSTRACT

OBJECTIVE:To study spectrum-effect relationship of 11 different solvent extracts from Trollius chinensis against hypoxia/reoxygenation injury of cardiomyocyte . METHODS :HPLC-MS/MS method was used to establish the fingerprints of 11 different solvent extracts from T. chinensis ,the compounds corresponding to the common peaks were identified by comparing with the substance control and literature information. MTT assay was used to detect the effects of 11 different solvent extracts from T. chinensis on the survival rate of rat myocardial H 9c2 cells injured by hypoxia/reoxygenation. The MDA content ,ROS level in cells and LDH content in the supernatant were detected by ELISA. GRA and PLS method were used to analyze the spectrum-effect relationship between the compounds corresponding to common peak and anti-hypoxia/reoxygenation injury of cardiomyocyte (drug effect). RESULTS :There were 22 common peaks in 11 different solvent extracts from T. chinensis ,and 22 compounds were identified. Compared with hypoxia/reoxygenation injury group ,survival rate of hypoxia/reoxygenation injury+S 1-S6,S9 and S 10 groups were increased significantly ,while MDA content ,ROS level and LDH content were decreased significantly (P<0.05); ROS level and LDH content of hypoxia/reoxygenation injury+S 8 group w ere decreased significantly (P<0.05). The r of GRA analysis of 22 compounds with drug effects were all higher than 0.8. Except for peaks 1,2,7,13,14 and 21,r of PLS analysis of rest peaks with drug effects were higher than 0 发。电话:0431-86058683。E-mial:nml2000@163.com (being positive correlation ). Top 9 common peaks in the list of contribution rate were peak 6>11>4>5>8>9>12>10>15. CONCLUSIONS :Orientin(peak 6),vitexin(peak 11), orientin-2″-O-β-L-galacto- pyranosl (peak 4),orientin-2″-O-β-D-Pyrine xylosides (peak 5),quercetin-3-O-glucopyranoside(peak 8),vitexin-2″-O-β-L-galactoside(peak 9),hyperoside(peak 12),vitexin-2″-O-β-D-pyrine xylosides (peak 10),2″-O-(2″′- methylbutyry-loxy)-orientin(peak 15)may be the main components of anti-hypoxia/reoxygenation injury of cardiomyocytes.

19.
Acta Pharmaceutica Sinica ; (12): 1431-1438, 2020.
Article in Chinese | WPRIM | ID: wpr-823315

ABSTRACT

Autophagy is a widespread and unique degradation process in eukaryotic cells. When cells are under various stress conditions such as nutritional deficiencies, growth factor deficiencies or hypoxia, autophagy will be initiated to maintain the stability of the internal environment and ensure normal proliferation and differentiation. At present, research on autophagy-related targets is mostly focused on tumor cells. In contrast, research on fungal autophagy targets is still limited. Autophagy plays an important role in growth, development and morphological changes of fungal cells, suggesting that research on fungal autophagy as a drug target should be useful. This article reviews the signal regulation and detection strategies for autophagy in fungal cells, and provides a research basis for the screening of antifungal drugs targeting autophagy-related proteins.

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Article in Chinese | WPRIM | ID: wpr-864571

ABSTRACT

Objective:To investigate the status of family function and self-care ability in elderly patients with total hip arthroplasty, and analyze the relationship between them.Methods:From March 2018 to March 2019, the convenience sampling method was used. 224 elderly patients undergoing total hip arthroplasty who were hospitalized in the orthopedics department of the Red Cross Hospital of Yulin City, Guangxi were selected as the research objects. The Family Function Assessment Form (APGAR) and the Self-care Capability Scale (ESCA) were used to survey patients ′ family functions and self-care capabilities. Results:The total score of family function of elderly patients with total hip arthroplasty was 8.16 ± 1.98, and those with good family function accounted for 71.88%(161/224); the total score of self-care ability was 84.32 ± 6.54. Those with moderat to low self-care ability accounted for 81.70%(183/224). Patients ′ family function was positively correlated with self-care ability ( P <0.05). Conclusions:The family function of elderly patients undergoing total hip arthroplasty is closely related to their self-care ability. Interventions should be taken to improve the family function of the patients and thus improve their self-care ability.

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