ArchiveThe perioperative brain injury is an important factor leading to poor clinical treatment effect and poor prognosis of critically ill patients undergoing cardiac surgery. In order to reduce the incidence of brain injury complications during perioperative period of cardiac disease, decrease the adverse consequence of brain injury, improve the neurological rehabilitation of patients after cardiac surgery, and enhance the quality of life and obtain the best prognosis of patients. Cardiac Intensive Care Professional Committee of Chinese Medical Doctor Association, Critical Care Medicine Professional Committee of Chinese Medical Education Association, Cerebral Protection in Cardiac Intensive Care Group of Neural Regeneration and Repair Committee of Chinese Research Hospital Association, and Liaoning Province Internet Intelligent Combination of Medical Care Professional Committee write the consensus. It aims to help clinicians improve the level of diagnosis and treatment of brain injury during perioperative period of cardiac critical care patients. The consensus include the characteristics and mechanisms of Chinese and Western medicine, monitoring methods, Chinese and Western medicine intervention and treatment of perioperative brain injury in adult cardiac surgery, thus providing apply reference for clinical work.
Objective To investigate the correlation between high-density lipoprotein cholesterol (HDL-C) levels and the risk of thyroid carcinoma in the population undergoing surgery for thyroid nodules. Methods The clinical data of 3996 patients who underwent thyroid surgery at the First Medical Center of PLA General Hospital from January 2016 to December 2020 were collected for retrospective analysis, 2846(71.2%) were females and 1150(28.8%) were males, including 3414(85.4%) thyroid carcinoma cases and 582 benign nodules (14.6%). The patients were divided into quintiles groups (Q1-Q5) according to HDL-C level from low to high. The clinical data characteristics of the five groups were compared, and multivariate logistic regression analysis was used to analyze the correlation between HDL-C level and thyroid carcinoma risk. A restricted cubic spline logistic regression model was established to analyze its dose-response relationship. Results As the level of HDL-C climbed from the first to the fifth quintile(Q1-Q5), the proportion of women in the study groups increased, whereas the proportions of thyroid carcinoma, body mass index(BMI), triglyceride levels and fasting blood glucose levels reduced significantly (P<0.05). After adjusting for confounding factors such as age, gender, BMI, thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and free triiodothyronine/free thyroxine (FT3/FT4) levels, the level of HDL-C remained a significant independent factor for thyroid carcinoma (OR=0.52, 95%CI 0.37-0.72, P<0.001). The trend test revealed statistically significant variations (P for trend <0.001). The E-value analysis indicated E=2.119. Compared with the study population with both TgAb and TPOAb being negative (OR=0.41, 95%CI 0.28-0.60, P<0.001) or positive for either antibody (OR=1.12, 95%CI 0.51-2.46, P=0.777), the correlation between HDL-C and thyroid cancer risk was stronger in patients with both TgAb and TPOAb being negative (P for interaction=0.014). A restricted cubic spline analysis revealed no nonlinear association between HDL-C levels and the risk of thyroid carcinoma in either men or women. Conclusion High HDL-C levels are associated with a lower risk of thyroid carcinoma in the population receiving surgery for thyroid nodules, particularly in patients with negative TgAb and TPOAb.
Objective To investigate the risk factors of lymph node metastasis in papillary thyroid carcinoma (PTC)patients who had thyroid nodule operation. Methods The clinical data of 4742 patients, who had surgical treatment for thyroid nodule from January 2016 to December 2020 in the First Medical Center of Chinese PLA General Hospital, were collected for retrospective study. The pathologic specimens of thyroid and lymph nodes of all the patients were retained during surgery. The patients were divided into metastasis group (n=2407) and non-metastasis group (n=2335) according to lymph node metastasis. The differences of age, sex, body mass index, thyroid stimulating hormone (TSH) value, tumor diameter, capsule invasion, and range of glandular lobe involvement were analyzed between the two groups. The independent risk factors for lymph node metastasis of papillary thyroid carcinoma were evaluated by logistic regression, and multivariate regression analysis were performed based on tumor diameter dividing into subgroups of small and non-small cancers. Results In 4742 patients with PTC, the incidence of cervical lymph node metastasis was 50.8% (2407 cases). Multivariate analysis showed that male, age <45 years, increased tumor diameter, external thyroid extension (ETE), and multiple tumors were independent risk factors for cervical lymph node metastasis(P<0.001). BMI (P=0.369), TSH level (P=0.246) and Hashimoto thyroiditis were not associated risk factors. Subgroup analysis showed that unilateral multiple foci was an independent risk factor for lymph node metastasis in non-microcarcinomas (OR=1.67, 95%CI 1.20-2.31, P=0.002), and ETE in microcarcinomas was also a risk factor for lymph node metastasis (OR=1.58, 95%CI 1.27-1.96, P<0.001). Conclusion Male, <45 years old, tumor size ≥9.5 mm, ETE and multiple tumors are independent risk factors for cervical lymph node metastasis in PTC patients.
Objective To explore the correlation between smoking status and the risk of papillary thyroid carcinoma(PTC) in patients undergoing surgical treatment for thyroid nodules. Methods A retrospective analysis was conducted with the clinical data of 5938 patients (5156 cases with PTC and 782 cases with benign nodules) who underwent surgical resection of thyroid nodules in the First Medical Center of Chinese PLA General Hospital from January 2016 to December 2020, and with complete postoperative pathological results. The general information, serum thyroid hormone (TSH) level, thyroid autoantibody level, and the clinical and pathological characteristics of patients with different smoking status were compared between the two groups. The correlation between smoking status and the risk of PTC in patients of different genders and overall population were analyzed using binary logistic regression analysis. Results There no significant difference in percentage of smokers between PTC group and benign nodule group (P=0.104). The PTC group had a significantly lower proportion of smokers than the benign nodule group for males (P<0.05) rather than for females (P>0.05). For all patients, smokers had a lower proportion of PTC than non-smokers(OR=0.735, 95%CI 0.564-0.959) after adjustment for confounders. In the gender subgroup analysis, a lower risk of PTC was found in smokers than in non-smokers among men (OR=0.635, 95%CI 0.449-0.896), while no association was observed among women(OR=0.910, 95%CI 0.417-1.986) after adjustment for confounders. Conclusion Smoking in males may be associated with a reduced risk of developing PTC in patients undergoing surgical treatment for thyroid nodules.
Objective To investigate the correlation between serum triglyceride (TG) levels and papillary thyroid carcinoma (PTC) in patients undergoing thyroid nodule surgery. Methods A retrospective analysis was conducted with the clinical data of 3340 patients with thyroid nodular disease [940 males (28.1%) and 2400 females (71.9%) with age of (44.5±11.4) years]who underwent thyroid nodule surgery and had complete operative blood lipid data in the First Medical Center of PLA General Hospital from January 2016 to December 2020. Based on the postoperative pathological condition, all the patients were divided into PTC group (2867 cases) and benign thyroid nodules group (473 cases). Analyze the general data of the two groups of patients using logistic regression to analyze the correlation between serum TG levels and the risk of PTC, and analyze the risk of PTC in age, gender, BMI, and thyroid autoantibody subgroups. Results Compared with benign nodules group, the serum TG levels of patients in PTC group were significantly higher [1.2(0.8, 1.7) vs. 1.1(0.8, 1.5), P<0.001]. Multivariate binary logistic regression analysis revealed that serum TG levels were associated with an increased risk of PTC disease (adjusted OR=3.067, 95%CI 1.839-5.116, P<0.001). Triglyceride levels were categorized into quartiles, with the lowest quartile serving as a reference. The relative risk for the highest quartile of triglycerides in PTC patients was 2.142(95%CI 1.548-2.965, P<0.001), and this association persisted even when serum triglycerides were within the normal reference range (adjusted OR=3.244, 95%CI 1.440-7.307, P=0.005). Subgroup analysis demonstrated that serum TG were associated with an increased risk of PTC only in patients with negative thyroid autoantibodies and a BMI<28 kg/m2 (P<0.05). Moreover, the risk of PTC was more pronounced in patients under 45 years of age compared with those aged 45 years and older (P for interaction=0.043). Conclusion Elevated serum triglyceride levels were associated with an increased risk of PTC in patients with negative thyroid autoantibodies and BMI<28 kg/m2.
Objective To explore the consistency of ultrasonography and histopathology in diagnosis of Hashimoto thyroiditis. Methods The clinical data of 6238 patients, who underwent surgical treatment for thyroid nodules in the First Medical Center of Chinese PLA General Hospital from January 2016 to December 2020, were collected and retrospectively analyzed. The preoperative thyroid function and ultrasound examination data of the included patients were complete, and the postoperative pathological results were clear. The effectiveness of ultrasound imaging in diagnosis of Hashimoto thyroiditis was analyzed, and the consistency between ultrasound and pathological diagnosis was evaluated by use of Cohen's kappa coefficient (κ). According to the preoperative thyroid stimulating hormone (TSH) level, the patients were divided into TSH elevated group (n=329), TSH normal group (n=5662) and TSH decreased group (n=247). The diagnostic efficacy of ultrasound examination under different preoperative thyroid function states and its consistency with pathological diagnosis were discussed. Results (1) Among the 6238 patients, preoperative ultrasound examination revealed 1549 cases of Hashimoto thyroiditis, and postoperative pathological diagnosis revealed 1182 cases of Hashimoto thyroiditis; Only 687 patients (58.1%) had positive ultrasound and pathological diagnoses. Among the confirmed patients, 88.7% were women (1048/1182) and 11.3% were men (134/1182); The three typical ultrasound manifestations in women, including reduced parenchymal echo (17.9% vs. 11.8%), grid like changes (7.5% vs. 4.7%), increased blood flow (14.5%vs. 8.3%, P<0.001), as well as the positive rate of ultrasound diagnosis (27.8% vs. 17.1%, P<0.001) and pathological diagnosis (23.3%vs. 7.7%, P<0.001), were significantly higher than those in men. (2) Consistency analysis showed that the consistency between ultrasound diagnosis and pathological diagnosis was general (κ=0.367). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ultrasound diagnosis were 58.1%, 83.0%, 44.4%, 89.4% and 78.2%, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of single imaging features (reduced parenchymal echo, grid like changes and increased) were 33.2%, 22.0%, 28.8%, 87.8%, 96.9%, 91.0%, 38.8%, 62.4%, 42.7% and 84.9%, 84.2%, 84.5%, respectively.The accuracy was 77.4%, 82.7% and 79.2%, respectively. Receiver operating characteristic (ROC) curve analysis showed that the predictive value of single imaging feature or the combination of two imaging features was poor in diagnosis. Among them, reduced parenchymal echo and reduced parenchymal echo combined with grid like changes were slightly better in diagnosis. (3) The positive rates of ultrasound and pathological diagnosis were higher in preoperative TSH elevated group and TSH decreased group (57.9% and 52.2% respectively in TSH elevated group; and 33.7% and 15.5% respectively in TSH decreased group, while TSH normal group was lower (22.9% and 17.7%, respectively). In addition, the consistency between ultrasound and pathological diagnosis in elevated TSH group was relatively the best, close to moderate (κ=0.399). Conclusions Both ultrasound diagnosis and single imaging features have good specificity and poor sensitivity in the diagnosis of Hashimoto thyroiditis. The consistency between ultrasound diagnosis and pathological diagnosis is general, and the consistency is slightly enhanced when combined with preoperative TSH elevation, but it can only be used as a reference. For female patients having thyroid dysfunction; the significance of combined ultrasound diagnosis will be greater. Ultrasonography is a convenient and quick supportive diagnosis of Hashimoto 's thyroiditis.
Objective To preliminarily observe the pyroptosis of splenic dendritic cells (DC) in septic mice and its correlation with the levels of inflammatory factors and DC immune function. Methods Seventy BALB/c mice were randomly divided into sham group (n=20), sepsis model group (CLP group, n=30) and caspase (CASP)-1 inhibit group (CLP+YVAD group, n=20). The CLP group and CLP+YVAD group were then divided into CLP 12 h group, CLP 24 h group, CLP 48 h group and CLP 72 h group, and CLP+YVAD 24 h group and CLP+YVAD 72 h group at different time points after operation. Orbital blood was collected from all mice at a predetermined time after operation, and the mice were sacrificed and spleen tissues were extracted. The pyroptosis rate of DC and the expression levels of DC surface markers (CD80, CD86, MHC-Ⅱ) were determined by flow cytometry.Activation of CASP-1 in mouse spleen DC was observed using confocal laser microscope. Western blotting was used to determine the expression of CASP-1 in DC. ELISA was performed to measure the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-12, IL-1β, and IL-6 in serum. Observe the death of mice after CLP operation. BALB/c mouse T cells were extracted and co-cultured with the mouse spleen DC of each group, the T cell proliferation rate was measured by flow cytometry, and the concentrations of interferon (IFN)-γ, IL-4 and IL-10 in the co-cultured supernatants were detected by ELISA. Results The pyroptosis rate of DC was increased 12 h after CLP compared to sham group (P<0.05), peaked at 24 h (P<0.01), and then progressively declined, but remained higher than sham group at 72 h after CLP (P<0.01). Confocal laser microscopy revealed that the activation of DC CASP-1 in spleen of mice after CLP was obvious. Western blotting showed the expression of CASP-1 in the early stage of sepsis (12 h and 24 h) was significantly higher than that in sham group (P<0.01). After administration of CASP-1 specific inhibitor Ac-YVAD-cmk, the DC pyroptosis rate at CLP+YVAD 24 h group was lower than that in CLP 24 h group (P<0.01). The expression levels of DC surface markers CD80 and MHC-Ⅱ at CLP+YVAD 72 h group were up-regulated compared with CLP 72 h group (P<0.01), and the survival rate of mice at 7 d after operation was improved (P<0.01). The results of ELISA showed that the concentrations of serum TNF-α, IL-12, IL-1β and IL-6 of CLP mice in the early stage (24 h) and late stage (72 h) of sepsis were significantly higher than those in sham group (P<0.01), while the serum concentrations of the above factors in CLP+YVAD group decreased significantly(P<0.01). In the co-culture experiment, compared with DC-CLP 24 h group, the T cell proliferation rate of DC-CLP+YVAD group significantly increased (P<0.01), the level of IFN-γ decrease in co-cultured supernatants, and the levels of IL-4 and IL-10 increased(P<0.01). Conclusions Pyroptosis of DC appears to be activated at the early stage upon septic challenge, might be an important pathophysiological mechanism with regard to the extensive release of inflammatory cytokines as well as immune suppression of DC, which is associated with poor prognosis of sepsis.
Objective To investigate the effects of mesenchymal stem cells (MSCs) on inflammatory factors and T-lymphocyte subsets in naturally aged sepsis rats. Methods Ninety naturally aged SD rats (21 months old) were divided into 3 groups according to the random number table method: 36 rats in the model group, 36 rats in the treatment group, and 18 rats in the sham group. In each group, animals were then randomly divided equally into three sub-groups. The rats were severed and executed after 6-h, 24-h, and 72-h anesthesia for modeling or treatment, respectively. The sepsis model was established by the cecum ligation perforation (CLP) method. The sham group was operated as the model group, except that the cecum ligation and perforation method was not used. After 1-hour of modeling, the rats in the treatment group were injected with umbilical cord MSCs through the tail vein, and the rats in the model group and the sham group were injected with the same volume of saline through the tail vein. The 72-hour survival rate of rats in each group was observed, and the levels of interleukin (IL)-1β, IL-6, IL-10, IL-17A, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β were measured by Aimplex method. The spleens of rats in each group were stained with TUNEL and the apoptosis of spleen lymphocytes was observed by laser confocal microscopy; the ratio of CD4+/CD8+ T cells in each group was analyzed by flow cytometry. Results The rats in the sham group showed no abnormalities during the observation period, and the survival rate at 72-hour after surgery was 100.00%. The rats in the model group showed symptoms such as vertical hair, loss of appetite, and depression after surgery, while these symptoms were improved in the treated rats, and the survival rate at 72-hour after CLP surgery was significantly higher in the treatment group than in the model group (66.67% vs.41.67%, P<0.01). Compared with the sham group, the model group showed increased levels of IL-1β, IL-6, and IL-17A, blurred spleen structure, increased proportion of apoptotic lymphocytes, and decreased proportion of CD4+/CD8+ T lymphocytes in peripheral blood and spleen, all with statistically significant differences (P<0.05). Compared with the model group, the treatment group showed reduced levels of IL-1β, IL-6 and IL-17A, increased levels of IL-10, clear spleen structure, significantly reduced lymphocyte apoptosis, and increased proportions of CD4+/CD8+ T lymphocytes in peripheral blood and spleen, all with statistically significant differences (P<0.05). Conclusions MSCs were able to significantly improve the survival rate of naturally aged sepsis rats, suppress excessive inflammatory responses, reduce lymphocyte apoptosis, and improve the immune function of the body, thus exerting a protective effect on naturally aged sepsis rats.
Objective To explore the differences in the intestinal flora between the glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH) rat model and its effect on the modeling results of GA-ONFH. Methods Forty SD rats were randomly divided into four groups (n=10 for each group): control group, antibiotic (ABX) group, GA-ONFH model group, and ABX+GA-ONFH group. The ABX group and ABX+GA-ONFH group were continuously treated with an antibiotic solution to elute intestinal microorganisms for one week. One week later, the GA-ONFH model group and ABX+GA-ONFH group were intraperitoneally injected with lipopolysaccharide and dexamethasone to create an early GA-ONFH model; while the control group and ABX group received an equal volume of normal saline for six weeks. After six weeks, to evaluate correlation between intestinal flora and GA-ONFH modeling, the following experiments were conducted and analyzed from intestinal contents and femur samples: 1) the composition and abundance of fecal flora based on 16S rDNA amplicon sequencing technology; 2) Micro-CT and HE staining to observe the modeling results of early GA-ONFH. Results Compared with control group, the abundance of intestinal flora in GA-ONFH model group changed, and the abundance of Bacteroidetes was significantly down-regulated and Firmicutes was significantly up-regulated, with statistical significance (P<0.05); at the family level, the abundance of Prevotellaceae, Clostridia-UCG-014, Peptococcaceae, Rikenellaceae, and Christensenellaceae were significantly down-regulated, the abundance of Staphylococcaceae was significantly up-regulated, and the differences were statistically significant (P<0.05); at the genus level, the abundance of Alistipes, UCG-005, Clostridia_UCG-014, Alloprevotella, and Prevotellaceae_UCG-001 were significantly down-regulated, the abundance of Staphylococcus and Frisingicoccus were significantly up-regulated, with statistical significance (P<0.05).Micro-CT tomography showed subchondral trabecular sclerosis in both the GA-ONFH model group and ABX+GA-ONFH group after modeling. HE staining showed that trabecular bone fracture occurred earlier in the ABX+GA-ONFH group than in the GA-ONFH model group. After the gut microbial abundance was removed, the rat GA-ONFH modeling effect was more significant. Conclusion The intestinal flora of GA-ONFH model rats changed, and the change of intestinal flora may affect the occurrence of early GA-ONFH.
Objective To analyze the mechanism of skeletal muscle atrophy in mice caused by Opg gene knockout based on metabolomics. Methods Five 3-month-old wild-type C57BL/6 male mice and five 3-month-old male Opg gene knockout mice were set as wild-type group and gene knockout group, respectively. Left femur and gastrocnemius muscle of mice were taken for evaluating the bone microstructure with micro-CT scanning and observing the morphological changes of gastrocnemius muscle by HE staining; The spermidine content in gastrocnemius muscle was detected by immunofluorescence staining. Ten 3-month-old male wild-type C57BL/6 mice, ten 3-month-old male Opg knockout mice and ten 18-month-old male wild-type C57BL/6 mice were set as young wild-type (WT-Y) group, young knockout (OPG-Y) group and old wild-type (WT-O) group, which were used for gastrocnemius metabolomics analysis. Results Compared with wild-type mice, Opg knockout mice showed fewer bone trabeculae, decreased bone density, cortical bone structure was destroyed, the weight of gastrocnemius muscle and the cross sectional area of gastrocnemius fiber were decreased (P<0.05). Metabolomics analysis showed that, compared with WT-Y mice, metabolites involved in glucose, phospholipid and amino acid metabolism, such as glucose-1-phosphate, D-glucose-1, 6-bisphosphate, multiple amino acids, choline, carnitine etc. were significantly up-regulated in WT-O mice, while γ-aminobutyric acid, spermidine, pantothenate etc. were significantly down-regulated. Compared with WT-Y mice, metabolites such as choline, β-glycerophosphate, azelaic acid etc. were up-regulated in OPG-Y mice, while other metabolites such as spermidine, pantothenate, N6, N6, N6-trimethyl-lysine etc. were significantly down-regulated, which were mainly involved in amino acid metabolism. The validation results of metabolomics analysis suggested that the content of spermidine in gastrocnemius of Opg knockout mice was significantly lower than that of WT-Y mice (P<0.01). Conclusion Opg knockout may regulate the levels of metabolites such as spermidine and regulate the level of metabolites such as spermidine and pantothenic acid through amino acid metabolism and other pathways, which cause skeletal muscle atrophy.
Objective To investigate the effect and potential mechanism of Taohong Siwu decoction(THD) on paclitaxel-induced peripheral nerve injury in rat. Methods Twenty-four female SD rats were randomly divided into control group, model group, THD low-dose group and THD high-dos group (6 each). Rats in control group were given saline of the same volume, while paclitaxel (8 mg/kg) was slowly injected intraperitoneally into rats in other three groups on the 1, 3, 5, and 7th day for 4 times. Rats with mechanical withdrawal threshold under 4 g indicated model success. The THD low-dose group and THD high-dose group was given 1 g/ml or 2 g/ml of THD 2 times/d, for 4 weeks. The threshold of mechanical stimulation, cold and hot stimulation to rats was detected after administration. The pathological morphology of sciatic nerve was observed by HE staining.The contents of inflammatory factor Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), thiobarbituric acid reactive substances (TBARS) and L-Glutathione (GSH) in the sciatic nerve were measured with automatic biochemical analyzer.The relative contents of myelination pieces were determined by red oil O staining and expression level of autophagy associated proteins microtubule-associated protein 1 light chain3-I (LC3-I), LC3-Ⅱ, and Beclin1 were detected by Western blotting. Results Compared with control group, rats in model group showed lower threshold to mechanical stimulation and lower sensitivity to hot and cold stimulation (P<0.05), expression levels of IL-6, TNF-α and TRABS elevated (P<0.05), while GSH levels decreased (P<0.05). HE staining showed tissue injury, atrophy, inflammatory infiltration, and myelination pieces increased significantly and expression of autophagy associated protein LC3-I, LC3-Ⅱand Beclin1 reduced (P<0.05). The results of THD low-dose group and THD high-dose group showed that the response of rats to mechanical stimulation, hot and cold stimulation was obviously improved (P<0.05), levels of IL-6, TNF-α and TRABS significantly decreased (P<0.05), while level of antioxidant GSH significantly elevated (P<0.05). Compared with THD low-dose group, rats in THD high-dose group showed elevated threshold to mechanical stimulation and more sensitive to mechanical stimulation, hot and cold stimulation (P<0.05), myelination pieces decreased significantly (P<0.05) and expression of autophagy associated protein LC3-I, LC3-Ⅱand Beclin1 increased (P<0.05). Conclusion Taohong Siwu decoction can alleviate rat peripheral nerve injury caused by paclitaxel, and its mechanism may be related to reducing inflammatory reaction and inducing autophagy to remove damaged debris.
Objective To investigate the regulatory effect and molecular mechanism of circAPLP2 on invasion and metastasis of colorectal cancer cell SW480. Methods The online database Starbase was used to predict the binding sites of circAPLP2 and miR-497-5p, and TargetScan was used to predict the binding sites of miR-497-5p and FGFR1. The relative expression levels of circAPLP2 and miR-497-5p in LoVo, DLD1, SW480, SW620, Caco-2 and HCoEpiC cells were detected by qRT-PCR, and the relative expression level of FGFR1 protein was detected by Western blotting. SW480 cells were taken and set up as follows:(1) siNC group (transfected with siControl) and sicircAPLP2 group (transfected with sicircAPLP2), the expressions of circAPLP2, miR-497-5p, FGFR1 mRNA were detected by qRT-PCR, and the expression of FGFR1 protein was detected by Western blotting.(2) Vector group (transfected with empty plasmid) and circAPLP2 group (transfected with circAPLP2 overexpression plasmid), the expressions of miR-497-5p and FGFR1 mRNA were detected by qRT-PCR, and the expression of FGFR1 protein was detected by Western blotting. (3) siNC group (transfected with siControl), sicircAPLP2 group (transfected with sicircAPLP2) and sicircAPLP2+miR-497-5p inhibitor group (transfected with sicircAPLP2 and miR-497-5p inhibitor), the cell invasion was detected by Transwell, the cell migration was detected by scratch test, and the expressions of EMT marker proteins (E-cadherin, Twist1, N-cadherin and Vimentin) were detected by Western blotting. (4) NC miRNA group (transfected with NC-miRNA) and miR-497-5p mimics group (transfected with miR-497-5p mimics), or NC-inhibitor group (transfected with NC-inhibitor) and miR-497-5p inhibitor group (transfected with miR-497-5p inhibitor), the expression of FGFR1 was detected by qRT-PCR and Western blotting.(5) pcDNA-Control group (transfected with pcDNA-Control) and pcDNA-FGFR1 group (transfected with pcDNA-FGFR1), the expression of FGFR1 protein was detected by Western blotting. (6) NC-miRNA group (transfected with negative control), miR-497-5p mimics group (transfected with miR-497-5p mimics) and miR-497-5p mimics+pcDNA-FGFR1 group (co transfected with miR-497-5p mimics and pcDNA-FGFR1), the cell invasion, migration and the expression of FGFR1 and EMT marker proteins(E-cadherin, Twist1, N-cadherin, Vimentin) were detected by Transwell, scratch test or Western blotting. The circAPLP2-WT or circAPLP2-MT report plasmid was co-transfected with NC-miRNA or miR-497-5p mimics respectively for 48 h in SW480 cells, and the FGFR1-WT or FGFR1-MT report plasmid was co-transfected with miR-497-5p mimics and circAPLP2 respectively for 48 h in SW480 cells, and the luciferase activity was detected by the luciferase reporter gene detection system. Results The analysis results by Starbase and TargetScan showed that binding sites existed between circAPLP2 and miR-497-5p, and between miR-497-5p and FGFR1. Compared with human colon epithelial cell HCoEpiC, the relative expression level of circAPLP2 in colorectal cancer cells LoVo, DLD1, SW480, SW620 and Caco-2 increased significantly, while of miR-497-5p significantly decreased, and the relative expression level of FGFR1 protein significantly increased (P<0.05). After knocking down the expression of circAPLP2, compared with siCN group, the number of invasive cells in sicircAPLP2 group decreased (P<0.001), and the cell healing rate of scratches decreased (P<0.001), the expression of E-cadherin protein increased, and the protein expressions of Twist1, N-cadherin and Vimentin decreased (P<0.05). The results of dual luciferase reporter assay showed that miR-497-5p mimics decreased circAPLP2-MT luciferase activity significantly (P<0.001); MiR-497-5p inhibitor reverses the inhibitory effect of sicircAPLP2 on EMT, migration and invasion of colorectal cancer cells, as the number of invasive cells increased (P<0.001), the scratch healing rate increased (P<0.01), the expression of E-cadherin protein decreased, and the expression of Twist1, N-cadherin, and Vimentin protein increased (P<0.05). Dual luciferase reporter assay results showed that miR-497-5p mimics significantly reduced FGFR1-MT luciferase activity (P<0.001). Over-expression of FGFR1 reversed the inhibition of miR-497-5p overexpression on colorectal cancer cell migration and invasion, manifested as increased number of invasive cells (P<0.001), increased scratch healing rate (P<0.01), decreased expression of E-cadherin, increased expressions of N-cadherin, Twist1 and Vimentin (P<0.05). Conclusion The expression level of circAPLP2 increases in colorectal cancer cells, it may promote the expression of FGFR1 through competitive combination with miR-497-5p, thus promoting EMT, invasion and migration of colorectal cancer cells.
Objective To evaluate the usability of tablet-based digital complex figure test (dCFT) software on assessment of drawing strategies of patients with amnestic mild cognitive impairment (aMCI). Methods A total of 64 patients treated in a hospital from Nov. 2020 to Nov. 2021 were selected, including 26 cognitively normal people (control group) and 38 aMCI patients(aMCI group). All subjects underwent standardized neuropsychological assessments, including the mini-mental state examination(MMSE), the montreal cognitive assessment (MoCA), the Rey–Osterrieth Complex Figure (ROCF) test, and other cognitive domain scales. And then use the dCFT (including copying and recall) developed by our team to collect drawing parameters, such as stroke length, time, speed and number. The Pearson correlation coefficient was used to evaluate the correlation between the original and simplified ROCF test scores, and partial correlation used to analyze the correlation between the dCFT parameters and the comprehensive scores of each cognitive domain. Results (1) In the copying test, all dCFT parameters had no statistically significant between the two groups (P>0.05). In the immediate recall test, the total thinking time and element delay time in aMCI group were significantly longer than those in the control group [27.15(21.49, 33.94) vs. 21.85(18.26, 24.81), 1.99(1.36, 3.62) vs.1.32(1.03, 1.99), P<0.05]. In the delayed recall test, the transition time of short and long stroke sequence, total thinking time, total completion time, first thinking time and element delay time of the aMCI group were significantly higher than those of control group [1.89(1.12, 3.93) vs. 1.19(0.42, 2.41), 23.94(18.86, 36.87) vs. 19.93(16.59, 23.00), 40.30(34.83, 56.21) vs. 34.52(29.96, 42.15), 7.92(6.20, 9.83) vs. 5.92(5.16, 8.04), 1.63(1.25, 2.47) vs. 1.08(0.83, 1.55), P<0.05]. The first 5 stroke ratios (%), speed of the longest stroke (cm/s) and strokes per minute of aMCI group were significantly lower than those of control group [60(40, 80) vs. 80(60, 100), 4.65(3.53, 6.07) vs. 6.00(4.54, 7.13), 21(18, 25) vs. 26(21, 27), P<0.05]. Other dCFT parameters had no statistically significance between the two groups (P>0.05). (2) Correlation analysis showed that the transition time was negatively correlated with attention and executive function (r=–0.292, r=–0.275, P<0.05); the speed of the longest stroke was positively correlated with the executive function (r=0.302, P<0.05); the total thinking time was negatively correlated with memory, attention, executive function and visuospatial ability (r=–0.26, r=–0.408, r=–0.448, r=–0.264, P<0.05); the total completion time was negatively correlated with attention, executive function and visuospatial ability (r=–0.342, r=–0.429, r=–0.273, P<0.05); the first stroke latency was negatively correlated with memory and visuospatial ability (r=–0.365, r=–0.407, P<0.01); the average element latency was negatively correlated with memory and attention (r=–0.377, r=–0.33, P<0.01); the strokes per minute was positively correlated with memory, attention, executive function and visuospatial ability (r=0.326, r=0.311, r=0.376, r=0.263, P<0.05). Conclusions Visuospatial memory impairment of aMCI patients was presented in 3-minute recall test of the complex figure test, and their drawing strategy was acceptable. But after 20 minutes, the memory and the organization strategy of drawing were significantly affected. Visual perception is not significantly impaired in the process. The dCFT software is a convenient, objective assessment tool for aMCI.
Objectives To understand the natural course of infection complications in elderly patients with tunnel-cuffed catheter (TCC) blood purification; and analyze the prognostic significance of blood routine test parameters detected before catheterization. Methods Collect 2430 patients who underwent blood purification treatment at the First Medical Center of the Chinese PLA General Hospital from January 2008 to January 2023, and follow up the patients who used TCC and had blood routine tests 24 hours before catheterization. Analyze the natural course of infection complications after TCC; Using all-cause death as the endpoint, Kendall correlation analysis was used to investigate the relationship between clinical data of first infection after TCC and prognosis. The nested case-control study was used to match the case group with the control group according to the ratio of hypertension and diabetes 1:1. The first infection within 6 months of TCC was taken as case group (n=34), and the first infection after 6 months of TCC was taken as control group (n=34). The risk factors related to the first infection within 6 months of TCC were analyzed by logistic regression. Validate the results of nested case-control studies across the entire group of patients and analyze the value of mean platelet volume (MPV) before catheterization in predicting the prognosis of first-time infections. Results A total of 77 patients were followed up, aged (78.4±7.3) years, with a median follow-up time of 28.0(13.8-70.5) months. After the first infection, 32 died and 45 survived. Compared with first-time infected survivors, deceased patients had a higher age and lower catheter age (P<0.05). The first infection within 6 months of TCC is positively correlated with death (r=0.336, P=0.003), and the cumulative survival rate is significantly lower than that in infected patients after 6 months of TCC (P<0.001). The results of a nested case-control study showed that the MPV of infected group within 6 months of TCC was significantly higher than that in control group [(10.64±1.05) fl vs. (9.89±0.80) fl, P=0.001]. Logistic regression analysis showed that the risk of infection was 3.222 times higher in high MPV group compared with control group. In the entire group of 77 cases, it was confirmed that high MPV values were associated with the occurrence of first infection within 6 months of TCC (P=0.037). Conclusions First infection within 6 months after TCC catheterization is associated with death; Patients with high MPV values before catheterization have a significantly increased risk of first infection within 6 months after TCC. The MPV level before catheterization may indicate a poor prognosis for infected individuals after TCC, and this indicator may be a personalized decision-making reference for TCC.
Cachexia is a serious chronic wasting syndrome, which is a common complication of cancer, end-stage heart failure and other diseases. The abnormal inflammatory response in the process of cachexia plays an important role in the loss of muscle and fat, the proliferation and metastasis of tumors. In recent years, it has been found that microRNA and long non-coding RNA (lncRNA) carried in exosomes can mediate cell-to-cell communication, activate related signaling pathway to secrete various inflammatory factors. It mediates the inflammatory response of cachexia, affects the formation of local and distal inflammatory microenvironment, promotes tumor cell proliferation, metastasis and inhibits its apoptosis, thereby accelerating the progression of cachexia. This review mainly summarizes the relationship between exosome and cachexia inflammation response, the harm of cachexia inflammation response and the mechanism of action, and provides new ideas for preventing it and slowing down the cachexia progress.
Liver fibrosis is a response to chronic liver injury caused by a variety of factors, such as alcohol consumption, viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD) and cholestatic liver disease. The combined effect of all these factors on the liver is to produce chronic inflammation leading to an abnormal wound-healing response. Mesenchymal stem cells (MSCs) are pluripotent stem cells that are able to implant into target tissues and secrete a variety of factors that can alter or improve the function of damaged tissues. Stem cells have the advantages of self-renewal, pluripotent differentiation and low immunogenicity. Due to their differentiation potential and paracrine characteristics, MSCs are the key for repair. This review focuses on the mechanism and progress of MSCs and their modifiers in liver fibrosis.
Acute respiratory distress syndrome (ARDS) refers to acute diffuse lung injury and subsequent acute respiratory failure caused by various intrapulmonary and extrapulmonary pathogenic factors, with respiratory distress and refractory hypoxemia as clinical features. At present, the "standardized" mechanical ventilation for ARDS patients is a lung protective ventilation strategy with low tidal volume and high positive end-expiratory pressure. However, the results are often unsatisfactory, and most related clinical studies have ended up unsuccessfully. Because of the high heterogeneity of ARDS, accurate classification and individualized treatment are very important. In this paper, we reviewed the phenotypes of ARDS from the perspectives of etiology, onset time, disease severity, inflammation level, imaging characteristics pathology, etc., and preliminarily explained the ARDS phenotype associated with COVID-19, and summarized the individualized treatment strategies for ARDS with different phenotypes, hoping to provide evidence for the individualized and precise treatment of ARDS.
corona virus disease 2019 (COVID-19), which emerged at the end of 2019, is caused by infection with the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). Due to the high mutability of SARS-COV-2, a variety of different types of mutant strains have emerged around the world, making the COVID-19 epidemic continues to spread around the world, posing a great threat and severe challenge to the global public health system. In November 2021, the Omicron (B.1.1.529)variant found in Botswana, southern Africa, is rapidly spreading globally with super infectivity, and has immediately attracted great attention worldwide because of its strong infectivity and immune evasion ability. In this paper, the latest research progresses on pathogenic characteristics, molecular mechanisms of immune evasion, vaccine tolerance and antibody tolerance of Omicron variant are briefly reviewed.