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AIM: To evaluate the clinical outcomes of using the cross-positioning method for correcting low and moderate astigmatism during small incision lenticule extraction(SMILE)surgery with Alpins vector analysis.METHODS: A total of 50 patients(81 eyes)with low and moderate astigmatism with the rule ≤1.50 D who underwent SMILE surgery at the laser myopia treatment center of Xi'an No.1 Hospital from May 2022 to November 2022 were included in the prospective randomized controlled study, and they were divided into two groups according to the random table, with 25 case(41 eyes)in cross-positioning group and 25 cases(40 eyes)in control group. In the cross-positioning group, the patients' head position was adjusted based on the cross intersection lines before the standard SMILE procedure, aligning the lateral canthi with the horizontal line and the midpoint of the eyebrows and the nose bridge with the vertical line. Postoperative visual acuity and refractive results at 3 mo were observed in both groups, and astigmatic changes were analyzed and evaluated using the Alpins vector analysis method.RESULTS: During the follow-up period, 6 cases(11 eyes)in the cross-positioning group were lost to follow-up, while in the control group, 8 cases(14 eyes)were lost to follow-up, with 19 cases(30 eyes)and 17 cases(26 eyes)finally included in the cross-positioning group and the control group, respectively. At 3 mo postoperatively, the uncorrected visual acuity(UCVA)of both groups' operated eyes was ≥1.0, and no serious complications occurred, with no significant differences in UCVA, best corrected visual acuity(BCVA), spherical power, and spherical equivalent between the cross-positioning group and the control group(all P>0.05). The cylindrical power in the cross-positioning group was 0.00(0.00, 0.00)D, which was lower than -0.13(-0.50, 0.00)D in the control group(P=0.01). The vector analysis results showed that the difference vector(DV)in the cross-positioning group was lower than that in the control group [0.00(0.00, 0.00)vs 0.13(0.00, 0.50), P=0.01], and the index of success(IOS)was better than that of the control group [0.00(0.00, 0.00)vs 0.18(0.00, 0.77), P<0.01]. At 3 mo postoperatively, 26(87%)and 15(58%)eyes in the cross-positioning group and control groups achieved an angle of error(AE)within ±5°, respectively.CONCLUSION: The cross positioning method was used to calibrate the patients' head position during SMILE surgery, which reduced the axial position error and improved the accuracy of SMILE in correcting low and moderate astigmatism.
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AIM:To evaluate corrective effect and stability of corneal morphology in patients with moderate to high myopia after 2a treatment of femtosecond laser assisted laser in situ keratomileusis(FS-LASIK)Xtra.METHODS:Retrospective case-control study. A total of 30 cases(58 eyes)Patients with moderate to high myopia combined with astigmatism who planned to undergo refractive surgery in our hospital from August 2019 to August 2020 were included, and different types of surgery were performed respectively based on the relevant index of keratoconus screening in the preoperative corneal topography. They were divided into FS-LASIK group and Xtra group, with 15 cases(29 eyes)in each group. Uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), spherical equivalent(SE)and the corneal curvature of the anterior and posterior surfaces of different diameters(3, 5 and 7 mm)measured by Sirius three-dimensional corneal topography were observed preoperatively and 3 mo, 1 and 2 a postoperatively.RESULTS: The UCVA of the two groups of patients at different time points after surgery was significantly increased compared with preoperatively(both P<0.01), and there was no difference in UCVA and SE between the two groups(P>0.05). After 2 a postoperatively, residual astigmatism was -0.25-0 D in 25 eyes(86%)of the FS-LASIK Xtra group and 24 eyes(83%)of the FS-LASIK group. The actual corrected SE and expected corrected SE of both groups were positively correlated(both P<0.05). There were differences in corneal curvature on the surface of different diameter areas(3, 5, and 7 mm)between the two groups at 3 mo, 1, and 2 a postoperatively compared with preoperatively. After 1 and 2 a postoperatively, the corneal posterior surface curvature of the FS-LASIK Xtra group with corneal diameter of 3 and 5 mm was higher than that of the FS-LASIK group(P<0.05).CONCLUSIONS:FS-LASIK Xtra has good safety, efficacy and predictability in correcting patients with moderate to high myopia.
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Aim To investigate the dynamic time-course changes in neuronal cytoskeleton after acute ischemia and reperfusion in rats. Methods Reperfusion was performedin rats by blocking the middle cerebralarteryfor 90 min, then therats wereobserved and collected at different time points. The brain damage wasobserved by Nissl staining,and neurobehavioural function was evaluated with neurological deficit score and forelimb placement test. The cellular changes in the alternations of cytoskeletal elements including microtubule associated protein 2 (MAP2) and neurofilament heavy chain (NF-H) were observed by immunohistochemistry staining and Western blot. Impaired axons, dendrites and cytoskeletal alternations were detected by electron microscope. Results Brain damage and neurobehavioural function were gradually aggravated with the prolongation of reperfusion. Brain damage appeared earlier and more severe in striatum than in cortex. Moreover, decreased MAP2-related and increased NF-H-related immunoreactive intensities were found in the ischemic areas. Impaired cytoskeletal arrangement and reduced dense were indicated. Damaged cytoskeletal components such as microtubules and neurofilament arrangement, decreased axonal filament density, and swelled dendrites were observed after cerebral ischemia reperfusion by ultrastructural observations. Conclusions Different brain regions have diverse tolerance to ischemia-reperfusion injury. Major elements of neuronal cytoskeleton show dynamic responses to ischemia and reperfusion, which may further contribute to brain damage and neurological impairment following MCAO and reperfusion.
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Aim To establish a stable hepatic stellate cell ( HSC ) -specific G protein-coupled receptor kinase 2 ( GRK2 ) knockout mice and provide the important animal model for further studying the biological function of GRK2 in HSC. Methods The loxP-labeled Grk2 gene mouse (Grk2
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Aim To investigate whether alisol A (AA) could improve the blood brain barrier (BBB) mediated cortex cerebral ischemia-repeifusion injury (CIRI) by inhibiting matrix metalloproteinase 9 (MMP-9). Methods The global cerebral ischemia- reperfusion (GCI/R) model in mice was established, and the AA was intragastric injected subsequently for seven days. The modified neurological severity scores (mNSS), open field test and Y-maze test were applied to detect neurological function. Magnetic resonance spectroscopy (MRS) was used to detect relevant neu- rosubstance metabolism in cortex of mice. Transmission electron microscope (TEM) was employed to observe the ultrastructure of BBB in cortex. Western blot and immunohistochemistry were used to detect the MMP-9 level in cortex. The binding possibility of A A and MMP-9 was determined by molecular docking. Results Compared with Sham group, mice in GCI/R group have an increased mNSS score but decreased at total distance and center distance to total distance ratio in open field test as well as alternation rate in Y-maze test (P<0.01). While mice in GCI/R + AA group have a decreased mNSS score but increased at total distance and center distance to total distance ratio in open field test as well as alternation rate in Y-maze test (P<0.01) compared with GCI/R group. MRS results found that in cortex of GCI/R group mice, the level of GABA and NAA significantly decreased while the Cho, mI and Tau level increased (P<0.01). Whereas in GCI/R + AA group mice, the GABA and NAA level increased and the Cho, ml and Tau decreased significantly (P<0.01). By TEM we observed that the basilemma of cerebral microvessels collapsed, the lumen narrowed, the endothelial cells were active and plasma membranes ruffled, gaps between cells were enlarged and tight junctions were damaged and the end feet of astrocytes were swollen in GCI/R group mice. While in GCI/R + AA group mice, the lumen was filled, plasma membranes of endothelial cells were smooth, tight junctions were complete and end feet of astrocytes were in normal condition. Western blot and immunohistochemistry both found that the MMP-9 level increased in GCI/R group mice (P < 0.01) and decreased in GCI/R + AA group mice (P < 0.05). Molecular docking proved the binding between aliso A and MMP9 through TYR-50 and ARG-106, and the binding energy was calculated as -6.24 kcal · mol
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Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2f/fLyz2-Cre+/- mice. Synovial inflammation and M1 polarization were improved in GRK2f/fLyz2-Cre+/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPARγ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPARγ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1+ macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA.
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Objective To analyze the correlation between uric acid and coronary atherosclerotic heart disease in adults. Methods A total of 186 patients with hyperuricemia from January 2020 to October 2021 were selected as the observation group and 186 subjects with normal blood uric acid were selected as the control group . The levels of uric acid, hs-CRP, MCP-1, IL-6, RANTES and adropin protein were measured . The SYNTAX score was used to assess the risk of coronary heart disease and the incidence rate of coronary heart disease was recorded. The correlation between uric acid and inflammatory indexes was analyzed by linear regression model . The relationship between serum uric acid level and coronary atherosclerotic heart was tested by spearman correlation test. Results The levels of hs-CRP, MCP-1, IL-6, RANTES and adropin protein in the observation group were higher than the control group significantly (P<0.05) . The syntax score of the observation group was higher than the control group significantly (P<0.05) .The incidence rate of coronary heart disease in the observation group was significantly higher than that in the control group, and the difference was statistically significant (P<0.05). The level of uric acid was significantly positively correlated with hs-CRP, MCP-1, IL-6, RANTES and adropin . There was positive correlation between serum uric acid and syntax score and the incidence of coronary atherosclerotic heart disease (P<0.05). Conclusion The increase of uric acid level can predict coronary atherosclerotic heart disease. Patients with hyperuricemia should actively carry out uric acid lowering treatment to prevent the risk of coronary atherosclerotic heart disease.
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AIM: To observe the epithelial remodeling of femtosecond laser-assisted stromal lenticule addition keratoplasty combined with corneal collagen cross-linking(SLAK-CXL)in patients with progressive keratoconus, investigate the remodeling rules of corneal epithelial and influencing factors, and provide clinical data for further refractive correction.METHODS: Retrospective and observational study. A total of 28 keratoconus patients(29 eyes)who received SLAK-CXL from September 2020 to October 2021 were included. Preoperative and postoperative visual acuity, intraocular pressure(IOP), diopter, keratometry and corneal epithelial thickness(CET)were recorded. The trend of CET change was observed. The factors affecting CET were analyzed according to the thickness and depth of the lenticule.RESULTS: Flattest meridian keratometry(Kf)and steepest meridian keratometry(Ks)at 1mo postoperatively were significantly larger than those preoperatively(P<0.05). The thinnest corneal thickness(TCT)at 1, 2, 6mo and 1a postoperatively were significantly larger than preoperative(P<0.05). The CET changed with time, with the central CET showing a larger variation tendency. The CET of superior, superior nasal, nasal, superior temporal in paracentral area were thinned, the CET of superior, temporal, superior temporal in midperipheral area were thinned, while the CET of superior nasal was thickened in peripheral area at 1, 2, 6mo and 1a postoperatively. The variation of CET was not correlated with the thickness or depth of lenticule at 1a postoperatively(P>0.05).CONCLUSIONS: It is firstly found that the corneal morphology has changed after SLAK-CXL. CET decreases and then increases and then decreases again. At 1a postoperatively, the CET of the central and paracentral areas is thinner, while the CET of the midperipheral and peripheral areas is thicker. The degree of epithelial remodeling is not correlated with lenticule thickness or depth.
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@#Objective To compare the spray characteristics of domestic and foreign nasal spray delivery devices for live attenuated influenza vaccine(LAIV). Methods The particle size distribution(DV10,DV50 and DV90),the proportion of droplets smaller than 10 μm and Span of atomized particles of two brands of nasal spray delivery devices at home and abroad were measured by laser diffraction method,the spray pattern[maximum diameter(D_(max)),shortest diameter(D_(min))and ovality(D_(max)/D_(min))]and spray geometry(spray angle and width)were detected by Spray view,and the comparative analysis was performed. Results There was no significant difference in DV10,DV50,DV90 particle size distribution,proportion of droplets smaller than 10 μm and Span of atomized particles between the two kinds of domestic and foreign nasal spray delivery devices[F-values of Levene's test for equality of variances were 0. 622,0. 135,3. 067,0. 212 and 0. 058,P-values were0. 434,0. 714,0. 085,0. 647 and 0. 810,and significance(two-tailed)values of equal variances assumed were 0. 439,0. 228,0. 281,0. 539 and 0. 910,respectively];D_(max),D_(min)and ovality of the spray patterns showed no significant difference[F-values of Levene's test for equality of variances were 2. 102,2. 666 and 0. 514,P-values were 0. 158,0. 114 and0. 479,and significance(two-tailed)values of equal variances assumed were 0. 651,0. 407,and 0. 160,respectively];The geometric mean ratios of spray angle and width were 0. 92 and 0. 91,respectively,which ranged from 0. 90 to 1. 11.Conclusion Both the domestic and foreign nasal spray delivery devices meet the delivery requirement of the nasal spray LAIV,which can be used for the delivery of nasal spray vaccines and drugs.
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Objective To investigate the material basis and antitumor mechanism of Marsdenia tenacissima (MT) on hepatocellular carcinoma (HCC) by bioinformatics, network pharmacology and molecular docking technology. Methods Active ingredients of MT were collected by literature search and screened by Swiss ADME website, which targets were predicted by Swiss Target Prediction. The chip data of HCC (GSE147888) were downloaded from the NCBI Gene Expression Omnibus (GEO) database. Differentially expressed genes were screened by R software. HCC-related targets were collected from the Genecards and OMIM databases. The Venny online tool was used to obtain the intersection of the herbal medicine targets and the disease targets. Subsequently, drug-target network and protein–protein interaction (PPI) network were constructed by Cytoscape software and String platform. GO enrichment analysis and KEGG pathway analysis were performed to analysis the functions and pathways enriched by key genes. The expression of key genes in HCC and its effect on survival were analyzed by the GEPIA database. The Human Protein Atlas (HPA) was used to analyze the immunohistochemical expression of key genes in HCC. Finally, molecular docking was carried out to investigate interactions between the top five targets and their related active compounds. Results A total of 50 active components were screened and 12 common targets were identified related to MT and HCC. Scutellarein-4-Methylether, Tenasogenin, Sinapic Acid, Dresgenin and Kaempferol were considered as the critical components. JUN, MMP9 and PTGS2 were recognized as key therapeutic targets. The GO analyses demonstrated that key targets mainly involved in the process of gene silencing and inflammatory response. KEGG analysis suggested that key targets were enriched in TNF signaling pathway and IL-17 signaling pathway. Survival analysis by the GEPIA showed significant differences in the expression of ESR1, MMP1, MMP9, JUN, and PPARG between high and low risk groups. Immunohistochemical results showed that ESR1 and MMP9 were differentially expressed in normal and hepatocellular carcinoma tissues. The molecular docking results verified that the drug active ingredient could be stably bound to the target protein. Conclusion This study reflected the multi-component, multi-target and multi-pathway characteristics of the MT in the treatment of HCC, which could provide a scientific basis for the clinical application of MT in HCC.
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Objective:To investigate the aspiration risk of preventive placement of nasal jejunum nutrition tube in advanced esophageal cancer patients receiving radiotherapy and the influencing factors.Methods:The clinical data of 220 patients with advanced esophageal cancer who received radiotherapy and preventive placement of nasal jejunum nutrition tube feeding from November 2020 to November 2021 in Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. The level of aspiration risk was measured according to the standard swallowing function assessment scale (SSA). The questionnaire collected the following data: (1) the general data including gender, age, educational level, history of smoking, history of alcoholism, knowledge of aspiration; (2) the disease factors including tumor staging, tumor site, swallowing function, abdominal distention; (3) the nosocomial factors including history of esophageal cancer surgery, sedation and analgesia treatment, combination of chemotherapy or not, cumulative radiotherapy dose, grade of radiation esophagitis, the position, time and tube feeding method of enteral nutrition. The standard swallowing function of patients was measured and repeated saliva swallowing test (RSST) was used to screen the patients with the difficulty in the esophageal function swallowing. Multiple linear regression was used to analyze the factors affecting aspiration risk.Results:A total of 220 patients with advanced esophageal cancer were enrolled in the investigation. Finally, 70 patients (31.8%) had grade 0 aspiration risk, and SSA score was 19; 23 patients (10.5%) had grade I aspiration risk, and SSA score was (23.4±1.3); 103 patients (46.8%) had grade Ⅱ aspiration risk, and SSA score was (27.5±1.1); 24 patients (10.9%) had grade Ⅲ aspiration risk, and SSA score was (33.2±1.5); 136 patients (61.8%) in total had aspiration risk. There were 32.7% (72/220) patients knowing the knowledge of aspiration. Multifactor analysis showed that esophageal tumor site ( t = -2.869, P = 0.005), cumulative radiotherapy dose ( t = 5.558, P < 0.001), grade of radiation esophagitis ( t = 11.405, P < 0.001), the duration time of enteral nutrition ( t = 4.050, P < 0.001) were independent factors affecting the aspiration risk. Conclusions:The aspiration risk of preventive placement of nasal jejunum nutrition tube in advanced esophageal cancer patients receiving radiotherapy is high, which is related to esophageal tumor site, grade of radiation esophagitis, cumulative radiotherapy dose and the duration time of enteral nutrition.
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Objective:To analyze the expression of cell division cycle associated protein 5 (CDCA5) in pancreatic cancer tissues and its correlation with prognosis based on the bioinformatics.Methods:The RNA sequencing data (HTSeq-FPKM) and corresponding clinical information of 168 pancreatic cancer samples from January to December 2021 were downloaded from the Cancer Genome Atlas (TCGA) database, and the data of 179 pancreatic patients from January to December 2021 were downloaded from the GEPIA2 database, and 171 normal pancreatic tissues from TCGA and GTEx databases were simultaneously integrated. The relative expression level of CDCA5 mRNA in pancreatic cancer patients in GEPIA2 database and its relationship with overall survival (OS) and disease-free survival (DFS) were explored. Combined with the clinical data of the patients, univariate and multivariate Cox regression model analysis was used to analyze the factors influencing the OS of pancreatic cancer patients. Gene set enrichment analysis (GSEA) was performed to investigate the possibly involved signal pathways of CDCA5 in pancreatic cancer.Results:In the GEPIA2 database, the relative expression level of CDCA5 mRNA in pancreatic cancer tissues was higher than that in normal pancreatic tissues, and the difference was statistically significant ( P < 0.05). The pancreatic cancer patients were divided into the high CDCA5 mRNA expression group (89 cases) and the low CDCA5 mRNA expression group (89 cases) according to the median of relative expression level of CDCA5 mRNA (the case equal to the median value was not subgrouped). Survival analysis showed that patients with high CDCA5 mRNA expression had shorter OS ( P = 0.024) and DFS ( P = 0.025) compared with those with low CDCA5 mRNA expression. Multivariate Cox analysis showed that in TCGA database, N staging ( HR = 2.15, 95% CI 1.24-3.72, P = 0.006) and CDCA5 expression ( HR = 1.71, 95% CI 1.23-2.38, P = 0.001) were independent influencing factors of OS for pancreatic cancer patients. The results of GSEA enrichment analysis indicated that high CDCA5 mRNA expression was enriched in 13 biological pathways [all P < 0.05, false discovery rate (FDR) < 0.005] including cell cycle, DNA replication, homologous recombination, pyrimidine metabolism, mismatch repair, pentose phosphate pathway, glycolysis gluconeogenesis and p53. The expression of CDCA5 mRNA was positively correlated with the expressions of HK2, PKM, PGK1, ALDOA, EN01 and LDHA (all P < 0.05). Conclusions:CDCA5 is highly expressed in pancreatic cancer tissues and is associated with poor prognosis of patients, and it can be used as a prognostic marker for pancreatic cancer.
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Objective:To investigate acute adverse events and pregnancy outcome after vaccination of inactivated COVID-19 vaccine in the first trimester of pregnancy.Methods:The retrospective-prospective cohort study was conducted among pregnant women of 11-13 +6 weeks of gestation who visited the obstetric clinics for prenatal check in Lianyungang Maternal and Child Health Hospital from May to November in 2021, after registration for perinatal health cards in the community. Those who met the inclusion criteria were recruited and were divided into vaccination group and non-vaccination group according to whether they received inactivated COVID-19 vaccine in the first trimester. Women in the vaccination group were further divided into 1-dose group and 2-dose group. Information, including pregnancy-related screening, pregnancy complications, pregnancy outcome and acute adverse events, were collected and compared with independent samples t-test or ANOVA, Kruskal- Wallis H test or Mann-Whitney U test, χ2 test or Fisher's exact probability method. Results:Totally, 105 pregnant women were analyzed in 1-dose group, 90 in 2-dose group, and 194 in non-vaccination group. (1) There were no statistically significant differences in the occurrence of acute adverse events [1-dose group: 2.86% (3/105); 2-dose group: 6.67% (6/90); non-vaccination group: 4.63% (9/194); χ2=1.59; vaccination group was 4.61% (9/195), when compared with non-vaccination group, χ2=0.00], abnormal pregnancy-related screening indicators and abnormal pregnancy outcome among the three groups (all P>0.05), neither between the vaccination and non-vaccination group (all P>0.05). The acute adverse events in these women included fever, pain at the inoculation site, fatigue, local induration and rash.(2) The differences in hypertensive disorders in pregnancy among the three groups were statistically significant [1-dose group: 10.5%(11/105); 2-dose group: 17.8%(16/90); non-vaccination group: 7.7%(15/194); χ2=6.46, P=0.040], and the incidence was higher in the 2-dose group than that in the non-vaccination group (adjusted by Bonferroni, P<0.017). (3) Regarding other pregnancy complications, no difference was found among the three groups (all P>0.05), neither between the vaccination and non-vaccination group (all P>0.05). Conclusion:The risk of acute adverse events and adverse pregnancy outcome is similar in pregnant women who received inactivated COVID-19 vaccine versus those who did not in the first trimester, and regular blood pressure monitoring is recommended for those who received two doses of inactivated COVID-19 vaccine.
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Objective:To investigate the Chinese anesthesiologist′s proficiency, training experience and needs of flexible bronchoscope-guided awake flexible bronchoscopy intubation (AFBI) using a questionnaire method.Methods:The cluster sampling was used, and self-designed questionnaires that addressed 54 questions in 5 categories were distributed through WeChat and online platforms. The survey took one month, and the answers were automatically recorded by the WeChat server.Results:A total of 1 250 anesthesiologists participated in the survey in 30 provinces of China, 9 of them were not anesthesiologists, and 1 241 (99.28%) questionnaires were validated. In the valid questionnaires, 52.70% (654) of the anesthesiologists were from tertiary hospitals, and 74.78% (928) of the anesthesiologists were attending physicians or above, only 7.57% (94) of the anesthesiologists had sufficient confidence in AFBI. Twenty-five point two two percent (313) of the anesthesiologists preferred fiberoptic intubation as the first tool when dealing with the anticipated difficult airway. Forty-eight point one one percent (597) of the anesthesiologists had implemented AFBI. Among them, 80.74% (482) had experienced unsuccessful AFBI practices. Eight hundred and ninety-four anesthesiologists had received AFBI training, and the most common AFBI training strategy was theoretical lectures. In addition, the degree of satisfaction regarding the theoretical lectures quality, technical training, clinical practice relativity and non-technical skills training was 21.47% (192), 14.32% (128), 12.3% (110) and 17.90% (160), respectively. The degree of satisfaction with all the 4 training elements mentioned above was 7.27% (65).Conclusions:The awareness and practice of Chinese anesthesiologists in terms of clinical application of AFBI to treat difficult airways need to be strengthened at present, and the lack of high-quality AFBI training may be the key.
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Objective:To explore the clinical features and prognosis of central nervous system involvement in patients with microscopic polyangiitis (MPA).Methods:We retrospectively investigated the clinical data of 138 MPA patients hospitalized with MPA in Tianjin Medical University General Hospital from January 1, 2010 to November 1, 2019. Patients were divided into two groups according to whether they had the central nervous system (CNS) involvement or not and then Kaplan-Meier survival curve was used to analyze the survival rate between the two groups, Logistic regression model analysis was adopted to analyze risk factors, and P<0.05 was considered statistically significant. Results:①29 patients (21.0%)among the 138 MPA had CNS-affected, including 13(44.8%) males and 16(55.2%) females. CNS involvement was present at the diagnosis of MPA in 20 cases (69.0%) and after the diagnosis of MPA in 9 cases (31.0%). ②The clinical manifestations were motor impairment in 14 cases (48.3%), sensory impairment in 10 cases (34.5%), speech loss in 9 cases (31.0%), headache in 8 cases (27.6%), consciousness disorder in 7 cases (24.1%), dysphagia and bucking in 4 cases (13.8%), cranial nerves involvement in 3 cases (10.3%). The imaging manifestations of the head included infarction, hemorrhage, infarction with hemorrhage and linear dural thickening. Five patients received lumbar puncture. One patient showed elevation of cerebrospinal fluid pressure, 1 patient had elevated protein and 5 patients showed elevation of LDH.③Eighteen patients received glucocortoid combined with cyclophosphamide. CNS symptoms recurred in 6 patients, four patients had recurrent cerebral infarction. ④Median survival time was 55 months in the CNS affected group [95% CI=(14.215, 95.785)] and 86 months in the N-CNS group [95% CI=(24.378, 147.622)]. Kaplan-Meier survival curve showed that there was no significant difference in survival rate between the two groups ( χ2=0.07, P=0.794) . Conclusion:The central nervous system involvement of microscopic polyangiitis is not uncommon. The clinical manifestations are various, with motor impairment the most. The most common imaging manifestation is cerebral infarction and the patients mainly presenteas multiple cerebral infarction. However, the CNS involvement of microscopic polyangiitis is not associated with mortality.
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Objective:To investigate the volume management of intermittent veno-venous hemofiltration (IVVH) guided by critical care ultrasound in the treatment of acute kidney injury (AKI) in patients with heart failure (HF).Methods:A total of 216 patients with HF and AKI treated with IVVH in the coronary care unit (CCU) of the Third Central Hospital of Tianjin from April 2019 to June 2022 were selected as the study subjects, the patients were randomly divided into conventional guidance group (107 cases) and ultrasound guidance group (109 cases). According to the recovery of renal function, IVVH was performed 12 hours every day or 12 hours every other day. The conventional guidance group selected the conventional method to formulate IVVH prescription, and the ultrasound guidance group used critical care ultrasound to adjust the treatment parameters of IVVH on the basis of the conventional guidance group. Respiratory variation index (RVI) of inferior vena cava (IVC), right left ventricular end-diastolic transverse area ratio, early diastolic peak mitral flow velocity/mitral annulus velocity peak (E/E'), aortic flow velocity time integral (VTI), cardiac output (CO), bilateral lung ultrasound B-line range, bilateral renal interlobar arteries resistance index (RI) were recorded before and 3, 6, 9 hours after each treatment. The net dehydration rate was adjusted in real time according to the comprehensive results. Urine volume, serum creatinine (SCr), estimated glomerular filtration rate (eGFR), blood B-type brain natriuretic peptide (BNP), β 2-microglobulin (β 2-MG) and cystatin C (Cys C) levels of patients in both groups were monitored before and 3, 7 and 10 days after initial treatment, and renal function recovery and clinical prognostic indexes of patients in both groups were recorded. Results:The dehydration rate of the ultrasound guidance group was slow at the beginning of IVVH, and gradually increased after 6 hours, and the overall dehydration rate was significantly slower than that of the conventional guidance group. In the ultrasound guidance group using critical care ultrasound, the RVI gradually increased, the right left ventricular end-diastolic area ratio gradually decreased, the E/E' ratio gradually decreased, and the range of B-line of bilateral lungs gradually decreased, RI of bilateral renal interlobar arteries decreased. At 3, 7 and 10 days after the first IVVH, renal function related indexes in both groups were significantly improved compared with before treatment, and the decline rate of β 2-MG and Cys C in the ultrasound guidance group was faster than that in the conventional guidance group at early (3 days) [β 2-MG (mg/L): 3.69±1.31 vs. 3.99±1.45, Cys C (mg/L): 2.91±0.95 vs. 3.14±0.96, both P < 0.05], urine volume, SCr and eGFR at 7 days were also significantly improved compared with the conventional guidance group [24-hour urine volume (mL): 1 128.23±153.92 vs. 1 015.01±114.18, SCr (μmol/L): 145.86±32.25 vs. 155.64±28.42, eGFR (mL/min): 50.26±11.24 vs. 46.51±10.61, all P < 0.05]. The time of SCr recovery, the time of reaching polyuria, the total time of IVVH treatment, the time of non-invasive mechanical ventilation and the time of living in CCU in the ultrasound guidance group were shorter than those in the conventional guidance group. The incidences of hypotension, long-term RRT, incidence of major cardiovascular adverse event (MACE) and at 28-day mortality were all lower than those in the conventional guidance group. Kaplan-Meier survival curve showed that the 28-day cumulative survival rate in the ultrasound guidance group was significantly lower than that in the conventional guidance group (Log-Rank test: χ 2 = 3.903, P = 0.048). Conclusion:The strategy of IVVH guided by critical care ultrasound in the treatment of HF with AKI has unique advantages.
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Objective:To analyze the clinical data of adult patients with brucellosis and provide scientific basis for treatment of brucellosis.Methods:The medical records of 1 279 adult brucellosis patients treated in the Brucellosis Department of Hulunbuir People's Hospital from January 2013 to December 2020 were selected. Epidemiological characteristics, clinical characteristics, laboratory examination, complications and curative effect were analyzed retrospectively.Results:Among the 1 279 cases of brucellosis, there were 797 males and 482 females, with an average age of (39 ± 15) years. There were 464 cases in acute stage, 815 cases in chronic stage, and 1 221 cases contacted with animal fur such as cattle, sheep and sheep skin. The main clinical manifestations were fatigue (974), fever (819), hyperhidrosis (674) and joint and muscle pain (752). Spleen enlargement was the most common sign, with 151 cases in sequence. There were 623 complications in 1 279 patients with brucellosis. Bone and joint damage, blood system damage and liver damage were more common, with 563, 298 and 264 cases, respectively. Some patients even had multiple system damage. The titer range of in vitro agglutination test (SAT) in 1 279 patients with brucellosis was 1 ∶ 50++ to 1 ∶ 1 600++; 198 cases were positive for Brucella in blood culture; SAT was positive in 8 cases of cerebrospinal fluid and 4 cases of pleural effusion. There were 114 cases of leucopenia, 51 cases of leucopenia, 158 cases of thrombocytopenia, 93 cases of decreased hemoglobin, 205 cases of elevated alanine aminotransferase, 198 cases of elevated aspartate aminotransferase and 143 cases of elevated creatinine in 1 279 patients with brucellosis. Erythrocyte sedimentation rate increased in 587 cases and C-reactive protein increased in 563 cases. After treatment with two or three antibiotics for at least 12 weeks, the total effective rate was 98.3% (1 257/1 279). Conclusions:The clinical manifestations of brucellosis are varied. Clinicians should highly suspect brucellosis if the patient has a history of epidemiological exposure to brucellosis and has symptoms such as fever, sweating, joint muscle pain and fatigue. Early diagnosis and standardized treatment should be carried out to prevent the disease from becoming chronic and affecting the quality of life. The occupational population should strengthen physical examination and education for brucellosis.
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Liver cancer is the second largest cancer in China, with the majority being hepatocellular carcinoma(HCC), which has a significant adverse impact on the lives and health of the Chinese people. Liquid biopsy is a new type of examination method with peripheral blood as the main examination subject. Compared with conventional tumor tissue pathology, liquid biopsy has less trauma, and the detection items can more accurately represent a certain tumor tissue group, more directly reflect the biological behavior of tumor tissue in the patient′s body. It is widely used in tumor screening, staging and grading, tumor individualized treatment monitoring, and prognosis evaluation. The following is mainly about the diagnosis, therapeutic effect evaluation and prognosis prediction of liquid biopsy in HCC from three aspects: circulating tumor DNA (ctDNA), exosome and circulating tumor cells (CTC), and the challenges faced by liquid biopsy technology at present are briefly described and its future development is prospected.
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In this study, a series of 18 histone deacetylases inhibitors (HDACis), derived from our in-house anti-cancer trans-β-arylacryl 1,2,3,4-tetrahydroisoquinoline-based scaffold, were designed, synthesized, and antitumor evaluated. HDAC1 inhibitory activity assay showed that compounds 13d-13f and 13m-13o demonstrated attractive enzymatic activity with IC50 at single-digit nanomolar or subnanomolar level.In addition, 13o exerted superior anti-proliferative activity (A549, IC50 = 0.89 μmol·L-1; HCT116, IC50 = 0.49 μmol·L-1) to that of vorinostat (SAHA).Besides,13e, with the most potent HDAC1 enzymatic activity (IC50 = 3.8 nmol·L-1), also displayed attractive cellular activity (A549, IC50 = 1.74 μmol·L-1; HCT116, IC50 = 2.43 μmol·L-1). The Western blot analysis illustrated that 13e treatment increased the acetylation of H3 and α-tubulin in a dose-dependent manner in A549 cells. In summary, 13e and 13o deserve further functional investigation.
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The oncogenic product of BCR-ABL is an abnormal tyrosine kinase that causes chronic myeloid leukemia (CML). With further research into the pathogenesis of CML, the discovery of compounds that selectively inhibit abnormal BCR-ABL tyrosine kinases is a research focus worthy of attention. The first three generations of BCR-ABL inhibitors are orthosteric inhibitors, which competitively block the binding of ABL protein tyrosine kinase to ATP and prevent it from activating downstream signals. The fourth-generation BCR-ABL inhibitors allosterically inhibit ABL protein tyrosine kinase by binding to the myristoyl pocket, providing greater selectivity and maintaining activity against drug-resistant mutations proteins. Novel drug design strategies such as proteolytic targeting chimera (PROTAC), covalent inhibitors and dual targeting inhibitors also provide new directions for the development of BCR-ABL kinase inhibitors. This paper reviews recent research advances on BCR-ABL kinase inhibitors and discusses drug design strategies for various novel BCR-ABL inhibitors.