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Abstract Introduction: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. Methods: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5'end or 3'end of TERC was detected. We recruited 100 patients of elective surgery. Results: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5' end or 3' end of TERC was not found. Conclusions: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.
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Humans , Aged , Propofol/pharmacology , Body Weight , DNA , Telomere , Anesthetics, Intravenous/pharmacology , Electroencephalography , Anesthesia, General , LeukocytesABSTRACT
Objective:To analyze the failure patterns and survival after stereotactic body radiotherapy (SBRT) in patients with T 1-2N 0M 0 non-small cell lung carcinoma (NSCLC). Methods:Clinical data of early-stage NSCLC patients who received SBRT at Zhejiang Cancer Hospital from January 2012 to September 2018 were retrospectively analyzed. The primary observed endpoint was the pattern of disease progression, which was divided into intra-field recurrence, regional lymph node recurrence and distant metastasis. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier method. Univariate analysis was conducted by log-rank test, and multivariate analysis was performed by Cox's model.Results:A total of 147 patients with 156 lesions were included. The median follow-up time was 44.0 months (16.5-95.5 months). A total of 57 patients (38.8%) progressed: 14 patients (24.5%) had recurrence with the 1-, 3-, and 5-year local recurrence rates of 2.0%, 10.9%, and 14.3%, respectively; 36 patients (63.2%) had Distant metastasis with the 1-, 3- and 5-year distant metastasis rates of 12.2%, 22.4% and 28.6%, respectively; and 7 patients (12.3%) had recurrence complicated with distant metastasis. The 3-, 5- and 7-year OS rates were 80.5%, 64.2% and 49.9% for all patients, respectively. The median OS was 78.4 months. The 3-, 5- and 7-year PFS rates were 64.8%,49.5% and 41.5%, with a median PFS of 57.9 months (95% CI: 42.3-73.5 months). Univariate and multivariate analyses showed that biologically equivalent dose and age were the factors affecting the efficacy of SBRT (both P<0.05). Conclusion:Distant metastasis is the main failure pattern in patients with T 1-2N 0M 0 NSCLC after SBRT. High-risk population should be selected for further systematic treatment to improve the efficacy.
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Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.
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ObjectiveTo understand the epidemic characteristics of notifiable infectious diseases （NIDs） other than coronavirus disease 2019 （COVID-19） in Shanghai in 2020， and to provide evidence for formulating infectious disease prevention and control strategies. MethodsData of NIDs reported in Shanghai from 2015 to 2020 were collected through the National Information System for Disease Control and Prevention. Descriptive epidemiological methods were used to analyze the incidence and prevalence characteristics of NIDs in Shanghai in 2020， and compared them with the average values of 2015 to 2019. ResultsA total of 45 574 cases of 23 kinds of NIDs were reported in Shanghai in 2020， except for COVID-19， with an incidence of 187.69/105， and a decrease rate of 50.58% compared with the average value of 2015 to 2019. The incidence of category B and C infectious diseases decreased by 38.07% and 57.47%， respectively （All P<0.001）. The top 3 reported infectious diseases with the highest incidence rate were influenza （64.58/105）， syphilis （39.09/105） and tuberculosis （24.90/105）. The incidence of most infectious diseases decreased compared with the average of 2015 to 2019， among which measles （97.15%）， rubella （88.81%）， pertussis （87.43%）， hand foot mouth disease （85.99%） and scarlet fever （79.84%） decreased significantly （all P<0.001）. In general， compared with the average from 2015 to 2019， respiratory infectious diseases declined most， followed by intestinal infectious diseases， insect-borne and natural focal infectious diseases， blood-borne and sexually transmitted diseases. Districts with higher incidence in 2020 were Fengxian District （310.23/105）， Xuhui District （271.93/105） and Hongkou District （254.38/105）. Respiratory infectious diseases in Fengxian District， intestinal infectious diseases in Jinshan District， blood-borne and sexually transmitted infectious diseases in Changning District， and insect-borne and natural focal infectious diseases in Yangpu District showed the highest incidence rate. Incidence of infectious diseases in 16 districts of Shanghai decreased with different degrees （all P<0.001）. Incidence of infectious diseases in males （209.44/105） was higher than that in females （164.89/105） （χ2=624.864， P<0.001）. Children aged 0-9 years had the highest incidence of respiratory and intestinal infectious diseases. People aged 70‒79 years and 20‒29 years had higher incidence of blood-borne and sexually transmitted infectious diseases， and people aged 20‒29 years had the highest incidence of insect-borne and natural focal infectious diseases. Majority of the patients were students （8 327 cases， 18.27%）， retired people （6 393 cases， 14.03%） and unemployed household workers （5 988 cases， 13.14%）. ConclusionUnder the COVID-19 prevention and control policies， the incidence of most NIDs in Shanghai decreased significantly in 2020.
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Disintegration time is a key parameter that affects the palatability and compliance of oral soluble films. At present, there is no standard method to determine the disintegration time of oral soluble films. In this study, we compared the six methods (pharmacopoeial disintegration method, petri dish method, sponge surface method, slide frame and ball method, partially immersed into liquid (without weight attached) and partially immersed into liquid (with weight attached)) to determine the in vitro disintegration time of oral soluble films with different thickness, and evaluated the correlation with the in vivo disintegration time. The results showed that the repeatability and correlation of pharmacopoeial disintegration method and the partially immersed into liquid method (with weight attached) were excellent, with the endpoint of disintegration testing easy to determine. Partially immersed into liquid method (with weight attached), properly simulating the physiological condition in oral cavity, showed strong operability, good repeatability and in vitro-in vivo correlation, and was suitable for in vitro disintegration evaluation of oral soluble film dosage form. The adult sensory evaluation study was a research-based clinical trial conducted with informed consent from all subjects in accordance with the ethical requirements of Good Clinical Practice.
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Licorzine granules are common preparations for children zinc deficiency. Considering the long course of treatment, the taste of licorzine granules may become a main factor affecting medication adherence. To date there have been no taste evaluation research into licorzine granules yet. In this study, both sensory evaluation and electronic tongue method were utilized to optimize licorzine granules formulations, evaluate the tastes of licorzine, excipients, optimized formulation in vivo and in vitro. As the results show, bitterness and astringency are the main unpleasant tastes generating from licorzine. Xanthan gum is the main taste-masking excipient, lowering down the bitterness and astringency of licorzine by at least one grade. Good correlation exists between the results of sensory evaluation and electronic tongue method, and an integrated combination of the two helps to obtain objective and rational research conclusions. The adult sensory evaluation study was a research-based clinical trial conducted with informed consent from all subjects in accordance with the ethical requirements of Good Clinical Practice.
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Inositol requiring enzyme 1 alpha (IRE1α), a widespread transmembrane protein in mammals, is an endoplasmic reticulum stress (ER stress) receptor. Among the three signaling pathways of the unfolded protein response (UPR), the IRE1α pathway is the most conservative. And there is a growing body of evidence that the occurrence and development of tumors is closely related to the over-expression of IRE1α. Therefore, the study of the IRE1α inhibitors is of great significance to the discovery of new anti-tumor drugs and has been attracting more and more attention. In the hope of providing ideas for the research of targeting IRE1α for cancer therapy, this paper reviewed the data of representative IRE1α inhibitors, including inhibitory activity, the mechanism of action, structural characteristics, and so on.
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Objective:To explore the relationship and underlying mechanism between exosomes derived from doxorubicin-resistant osteosarcoma cells and MDR1 and miRNAs. Methods:MG63 and U2OS cell lines were selected to construct doxorubicin-resistant strains, and the 50% inhibitory concentration (half maximal inhibitory concentration, IC 50) of drug-resistant and sensitive strains was detected by MTT, and fluorescence staining was performed at intervals of 15 min between 15 and 120 min to detect the change of fluorescence intensity. RT-PCR and Western Blot were used to detect the expression levels of MDR1 P-gp to verify the drug resistance of osteosarcoma cells. Exosomes were identified by particle size analysis and Western Bolt detection. The endocytosis of PKH26-labeled exosomes from doxorubicin-resistant cells was observed, and the proliferation level and migration of exosomes from doxorubicin-resistant cells co-cultured with osteosarcoma cells were detected by MTT assay and cell scratch assay. The differential expression levels of miRNAs in osteosarcoma-sensitive and drug-resistant cells were verified by sequencing and bioinformatics analysis and RT-PCR assay. Tumor growth, serum exosome identification and mRNA expression level of miR-21-5p in tumor-bearing nude mice between normal osteosarcoma cell group and drug-resistant group, drug-resistant+normal exosome group, drug-resistant+drug-resistant+drug-resistant exosome group were observed. MDR1 expression level in tumor tissue was detected by RT-PCR, Western Blot and immunohistochemistry. Results:The IC 50 of two adriamycin resistant strains were 2.21 vs. 11.81 μg/ml and 0.93 vs. 11.81 μg/ml, respectively, and the fluorescence intensity decreased faster than that of normal strains. The relative mRNA expression levels of MDR1 in two cell lines were normal 1.12±0.16, 1.02±0.11 and drug-resistant 2.15±0.10, 2.127±0.12, respectively. The relative protein expression of P-gp was normal 0.92±0.11, 0.73±0.10 and drug-resistant 0.46±0.03, 0.30±0.04, the differences were statistically significant ( P<0.05). Drug-resistant exosomes can enter osteosarcoma cells through endocytosis and concentrate in the cytoplasm when co-cultured with normal strains. Osteosarcoma cells were co-cultured with drug-resistant exosomes at 2, 4, 6, and 8 μg/ml adriamycin, respectively. Compared with normal group, the proliferation level in drug-resistant group was significantly increased. Compared with the normal cell group 35.95±3.92, 6.72±3.55 and the normal exosome group 51.22±5.55, 19.31±1.93, the drug-resistant cell group 54.20±9.32, 19.24±2.88 and drug-resistant exosome group 76.40±5.41, 30.26±4.87, all had significantly higher cell mobility, the difference was statistically significant ( P<0.05). Exosome sequencing and biogenic analysis of 10 highly upregated miRNAs to validate mRNA expression differences between normal and drug-resistant strains by RT-PCR, showing a significant increase in miR-21-5p expression level of drug-resistant strains (5.89±0.26 vs. 0.99±0.06; 1.05±0.07 vs. 8.80±0.93, P<0.05), the difference was statistically significant ( P<0.05). In MG63 and U2OS, the normal cell group and drug-resistant cell group, and the normal exosome group and drug-resistant exosome group were compared, the tumor volume and the terminal tumor weight of nude mice were increased to varying degrees. MRNA relative expression levels of miR-21-5p in serum exosomes of nude mice after drug intervention were 0.86±0.07 and 0.86±0.05 in normal cell group, respectively. The values were 1.13±0.12, 1.14±0.12 in drug-resistant cell group, 0.71±0.05, 0.75±0.03 in normal exosome group, and 0.90±0.07, 0.93±0.04 in drug-resistant exosome group. Compared with normal and drug-resistant strains, the expression levels of normal and drug-resistant exosome groups were increased, with statistical significance ( P<0.05). Conclusion:The exosomes of drug-resistant cells in osteosarcoma could enhance the proliferation level and migration ability of cells through intercellular transfer of MDR1 and miRNAs. The expression of MDR1 and miR-21-5p in drug-resistant cells and tumor-forming nude mouse serum and tumor tissues were up-regulated which suggested that it might be involved in regulating the drug resistance process of osteosarcoma.
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@#Abstract: Objective To investigate the influence of the variation of SARS-CoV-2 on the clinical feature, and to provide early warning signs for the variation of SARS-CoV-2 in clinical work. Methods From Jan 2, 2021 to Jun 30, 2021, a total of 105 COVID-19 patients were included in the study using a case-control method. Nasal swab samples were collected from the study subjects, the viral genes were sequenced, and patients were divided into Delta variant group and non-Delta variant group according to their gene sequences. Clinically relevant data were collected from the two groups, and indicators such as days of hospitalization, age distribution, lymphocytes, neutrophils, B lymphocytes, NK cells, IL-4, and IL-10 were compared; subgroup analysis was performed based on the number of days of viral negativity in the study subjects as the basis for grouping, and differences in immunological characteristics were compared, including lymphocytes, neutrophils, B lymphocytes, NK cells, IL-4, IL-10, etc. Results The theoretical hospitalization days of Delta variant group were (22.2±8.33) d, which were significantly longer than (17.6±10.50) d of non-Delta variant group (t=2.396, P<0.05). The total lymphocyte count and IL-4 of Delta variant group were (1.22±0.86) ×109/L and (0.80±0.23) ng/mL, which were significantly lower than corresponding (1.91±0.70) ×109/L and (1.59±0.59) ng/mL of non-Delta variant group (t=4.329, 9.072, P<0.05), while IL-10 was (7.16±7.77) ng/mL, which was significantly higher than (4.26±3.91) ng/mL of non-Delta mutation group (t=1.980, P<0.05). Subgroup analysis showed that the total lymphocyte count and IL-4 concentration in Delta variant group were (1.04±0.60) ×109/L and (0.74±0.25) ng/ml, which were significantly lower than corresponding (1.62±0.56) ×109/L and (1.56±0.52) ng/mL in non-Delta variant group, in patients with delayed discharge (P<0.05). Conclutions SARS-CoV-2 variant has an impact on clinical manifestations. The patient's B cell count and IL-10 concentration increased or IL-2 and IL-4 concentration decreased within 12 hours of admission indicated variant virus infection. The decrease of total lymphocyte count, especially T lymphocyte reduction, strongly suggests discharge delay due to viral clearance disorder.
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Objective@#To investigate the characteristics of HIV/AIDS cases among 15-24 year old population reported in Hefei from 2004 to 2022, so as to provide insights into AIDS control among adolescents.@*Methods@#The epidemiological data regarding HIV/AIDS cases between 15 and 24 years old reported in Hefei from 2004 to 2022 were captured from the AIDS comprehensive prevention and control information system of Chinese disease prevention and control information system, and data regarding temporal distribution, population distribution, and routes of infections and detection were descriptively analyzed by descriptive epidemiological methods.@*Results@#From 2004 to 2022, 865 cases of HIV/AIDS were reported in Hefei among 15-24 years old youth, accounting for 21.80% of the total reported cases. Among the HIV/AIDS patients, males accounted for 92.60%(801 cases), the unmarried ones accounted for 93.41% (808 cases)，those with college degree or above accounted for 60.12% (520 cases)，and 25.78%(223 cases) of them were students. The proportion of student cases increased annually( χ 2 trends =47.67, P <0.01). Homosexual transmission accounted for 81.39%, both showed an increasing trend( χ 2 trends =51.23, P <0.01)．Totally 55.49% of cases were found through testing and consultation, and the proportion of cases increased by year( χ 2 trends =112.18, P <0.01). In 2004-2022，the number of newly reported cases among people aged 15-24 showed a rising trend at an average rate of 24.46% by year( Z=4.92, P <0.01), which was higher than the average rate of 21.54% for the entire population( Z=12.75, P <0.01).@*Conclusion@#The epidemic of HIV/AIDS among population aged 15-24 years is serious in Hefei. Comprehensive measures for HIV education and prevention intervention are desperately needed to be reinforced among targeted students.
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ObjectiveThe glymphatic system regulates cerebral spinal fluid and interstitial fluid transport which might be one of the pathways of central nervous system （CNS） leukemia at the early stage. This study aimed to investigate the alteration of glymphatic system based on diffusion tensor image-analysis along the perivascular space （DTI-ALPS） in pediatric acute lymphoblastic leukemia （ALL） without clinically diagnosed CNS infiltration. MethodsTwenty-five ALL and typically developing （TD） children were prospectively recruited， and all subjects underwent DTI. Group differences in brain water diffusivities and ALPS-index were evaluated using the analysis of covariance. The Spearman correlation analysis was used to evaluate the relationship between biological characteristics and significant parameters in pediatric ALL. ResultsCompared with TDs， decreased Dxassoc value （PFDR-corrected = 0.048） and increased Dzassoc value （PFDR-corrected = 0.033） were found in pediatric ALL. Hence， lower ALPS-index was found in children with ALL （PFDR-corrected < 0.001）. ALPS-index was negatively associated with the risk classification （rs = -0.47， P = 0.018） as well as immunophenotype （rs = -0.40， P = 0.046） in pediatric ALL. ConclusionsOur results show dysfunction of the glymphatic system is presented in pediatric ALL without clinically diagnosed CNS infiltration， which suggests that the glymphatic system might be one of pathway in the early-stage of ALL CNS infiltration. The DTI-ALPS method can be used to evaluate the change of glymphatic system， providing a new method for exploring the underlying mechanisms and early detection of pediatric ALL CNS infiltration.
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AIM: To compare the effectiveness and complications of treating rhegmatogenous retinal detachment(RRD)with foldable capsule body(FCB)and scleral buckling(SB).METHODS: The clinical data of 81 patients(82 eyes)with RRD who underwent surgery at our hospital from March 2019 to April 2022 were retrospectively analyzed. The differences in retinal reattachment rate, best-corrected visual acuity, the absorption of subretinal fluid, postoperative discomfort and incidence of complications between the two treatments were compared.RESULTS: The retinal reattachment rate was 96% in the FCB group and 92% in the SB group, with no significant difference between the two groups(P>0.05). The best corrected visual acuity of the affected macular eyes was different in the both groups(P<0.01). Both groups effectively promoted the absorption of subretinal fluid. The operation time of FCB group was 16.50(12.75, 25.00)min, while it was 38.00(36.25, 41.75)min in the SB group(P<0.001). Patients in the FCB group also had significantly lower eyelid swelling and pain symptoms than those in the SB group(P<0.001). The visual analogue scale(VAS)score at 1d after operation was 1.00(0.00, 2.00)in the FCB group and 3.00(2.00, 3.00)in the SB group(P<0.001).CONCLUSION: FCB is a safe and effective surgical method to treat RRD that can alleviate patient's pain. Furthermore, FCB has a significantly shorter operation time and milder postoperative adverse reactions than SB.
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OBJECTIVE@#To analyze the cement flow in the abutment margin-crown platform switching structure by using the three-dimensional finite element analysis, in order to prove that whether the abutment margin-crown platform switching structure can reduce the inflow depth of cement in the implantation adhesive retention.@*METHODS@#By using ANSYS 19.0 software, two models were created, including the one with regular margin and crown (Model one, the traditional group), and the other one with abutment margin-crown platform switching structure (Model two, the platform switching group). Both abutments of the two models were wrapped by gingiva, and the depth of the abutment margins was 1.5 mm submucosal. Two-way fluid structure coupling calculations were produced in two models by using ANSYS 19.0 software. In the two models, the same amount of cement were put between the inner side of the crowns and the abutments. The process of cementing the crown to the abutment was simulated when the crown was 0.6 mm above the abutment. The crown was falling at a constant speed in the whole process spending 0.1 s. Then we observed the cement flow outside the crowns at the time of 0.025 s, 0.05 s, 0.075 s, 0.1 s, and measured the depth of cement over the margins at the time of 0.1 s.@*RESULTS@#At the time of 0 s, 0.025 s, 0.05 s, the cements in the two models were all above the abutment margins. At the time of 0.075 s, in Model one, the gingiva was squeezed by the cement and became deformed, and then a gap was formed between the gingiva and the abutment into which the cement started to flow. In Model two, because of the narrow neck of the crown, the cement flowed out from the gingival as it was pressed by the upward counterforce from the gingival and the abutment margin. At the time of 0.1 s, in Model one, the cement continued to flow deep inside with the gravity force and pressure, and the depth of the cement over the margin was 1 mm. In Model two, the cement continued to flow out from the gingival at the time of 0.075 s, and the depth of the cement over the margin was 0 mm.@*CONCLUSION@#When the abutment was wrapped by the gingiva, the inflow depth of cement in the implantation adhesive retention can be reduced in the abutment margin-crown platform switching structure.
Subject(s)
Finite Element Analysis , Cementation/methods , Gingiva , Crowns , Dental Abutments , Dental Cements , Dental Stress AnalysisABSTRACT
Acute-on-chronic liver failure (ACLF) is a potentially reversible entity that occurs in patients with chronic liver disease accompanied with or without cirrhosis and is characterized by extrahepatic organ failure and high short-term mortality. Currently, the most effective treatment method for patients with ACLF is liver transplantation; therefore, admission timing and contraindications must be emphasized. The function of vital organs such as the heart, brain, lungs, and kidneys should be actively supported and protected during the liver transplantation perioperative period in patients with ACLF. Focusing on the anesthesia management level during anesthesia selection, intraoperative monitoring, three-stage management, prevention and treatment of post-perfusion syndrome, monitoring and management of coagulation function, volume monitoring and management, and body temperature monitoring management for liver transplantation should strengthen anesthesia management. Additionally, standard postoperative intensive care treatment should be recommended, and grafts and other vital organ functions should be monitored throughout the perioperative period to promote early postoperative recovery in patients with ACLF.
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Humans , Liver Transplantation , Acute-On-Chronic Liver Failure/surgery , Liver Cirrhosis/complications , Perioperative Period , PrognosisABSTRACT
Objective: To study the construction of a prognostic model for hepatocellular carcinoma (HCC) based on pyroptosis-related genes (PRGs). Methods: HCC patient datasets were obtained from the Cancer Genome Atlas (TCGA) database, and a prognostic model was constructed by applying univariate Cox and least absolute shrinkages and selection operator (LASSO) regression analysis. According to the median risk score, HCC patients in the TCGA dataset were divided into high-risk and low-risk groups. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, univariate and multivariate Cox analysis, and nomograms were used to evaluate the predictive ability of the prognostic models. Functional enrichment analysis and immune infiltration analysis were performed on differentially expressed genes between the two groups. Finally, two HCC datasets (GSE76427 and GSE54236) from the Gene Expression Omnibus database were used to externally validate the prognostic value of the model. Univariate and multivariate Cox regression analysis or Wilcoxon tests were performed on the data. Results: A total of 366 HCC patients were included after screening the HCC patient dataset obtained from the TCGA database. A prognostic model related to HCC was established using univariate Cox regression analysis, LASSO regression analysis, and seven genes (CASP8, GPX4, GSDME, NLRC4, NLRP6, NOD2, and SCAF11). 366 cases were evenly divided into high-risk and low-risk groups based on the median risk score. Kaplan-Meier survival analysis showed that there were statistically significant differences in the survival time between patients in the high-risk and low-risk groups in the TCGA, GSE76427, and GSE54236 datasets (median overall survival time was 1 149 d vs. 2 131 d, 4.8 years vs. 6.3 years, and 20 months vs. 28 months, with P = 0.000 8, 0.034 0, and 0.0018, respectively). ROC curves showed good survival predictive value in both the TCGA dataset and two externally validated datasets. The areas under the ROC curves of 1, 2, and 3 years were 0.719, 0.65, and 0.657, respectively. Multivariate Cox regression analysis showed that the risk score of the prognostic model was an independent predictor of overall survival time in HCC patients. The risk model score accurately predicted the survival probability of HCC patients according to the established nomogram. Functional enrichment analysis and immune infiltration analysis showed that the immune status of the high-risk group was significantly decreased. Conclusion: The prognostic model constructed in this study based on seven PRGs accurately predicts the prognosis of HCC patients.
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Humans , Carcinoma, Hepatocellular/genetics , Prognosis , Pyroptosis , Liver Neoplasms/genetics , Risk FactorsABSTRACT
Objective: To investigate the distribution and characteristics of gene mutations in osteosarcoma, and to analyze the frequency and types of detectable mutations, and to identify potential targets for individualized treatment of osteosarcoma. Methods: The fresh tissue or paraffin-embedded tissue samples of 64 cases of osteosarcoma that were surgically resected or biopsied and then subject to next generation sequencing, were collected from Beijing Jishuitan Hospital, China from November 2018 to December 2021. The tumor DNA was extracted to detect the somatic and germline mutations using targeted sequencing technology. Results: Among the 64 patients, 41 were males and 23 were females. The patient age ranged from 6 to 65 years with a median age of 17 years, including 36 children (under 18 years old) and 28 adults. There were 52 cases of conventional osteosarcoma, 3 cases of telangiectatic osteosarcoma, 7 cases of secondary osteosarcoma, and 2 cases of parosteosarcoma. The detection rate of gene mutations was overall 84.4% (54/64). There were 324 variations in 180 mutated genes, including 125 genes with copy number variations, 109 single nucleotide variants, 83 insertions or deletions, and 7 gene fusions. The most common mutated genes were TP53, VEGFA, CCND3, ATRX, MYC, RB1, PTEN, GLI1, CDK4 and PTPRD. Among them, TP53 had the highest mutation rate (21/64, 32.8%), single nucleotide variant was the main mutation type (14/23, 60.9%), and 2 cases carried the TP53 germline mutation. VEGFA and CCND3 showed copy number amplification simultaneously in 7 cases. Conclusions: The high-frequency mutation of TP53 suggests that it plays an important role in the pathogenesis and development of osteosarcoma. VEGFA, CCND3 and ATRX are mutated genes in osteosarcoma and worthy of further studies. Combination of pathologic diagnosis and next generation sequencing with clinical practice can guide individualized treatment for patients with refractory, recurrent and metastatic osteosarcoma.
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Adult , Male , Child , Female , Humans , Adolescent , Young Adult , Middle Aged , Aged , DNA Copy Number Variations , Osteosarcoma/pathology , Mutation , DNA, Neoplasm , High-Throughput Nucleotide Sequencing , Bone Neoplasms/pathology , NucleotidesABSTRACT
ObjectiveCentral nervous system （CNS） infiltration commonly occurs in children with acute lymphoblastic leukemia （ALL）. Early subclinical CNS infiltration in pediatric ALL is hard to detect with conventional methods. This study aimed to investigate the changes of brain structure volume parameters based on Synthetic MRI （SyMRI） in pediatric ALL without clinically diagnosed CNS infiltration. MethodsThirty-six ALL and twenty-nine typically developing （TD） children were prospectively collected and all underwent SyMRI. The Synthetic MR software was used to obtain brain volumetric parameters including total white matter volume （WMV）， gray matter volume （GMV）， cerebrospinal fluid （CSF） volume， etc. and their within-group differences were assessed by analysis of covariance. The Spearman correlation analysis was used to examine the correlation between biological characteristics and statistically significant brain volume parameters. ResultsALL children showed increased CSF volume （PFDR-corrected = 0.009） and decreased GMV （PFDR-corrected = 0.027） when compared to TD children. We also found a moderately negative association between GMV/intracranial volume and risk classification in pediatric ALL （rs = -0.380， P = 0.022）. ConclusionsPediatric ALL without clinically diagnosed CNS infiltration presented with accumulation of CSF and reduction of gray matter. The brain volumetric changes in subclinical CNS infiltration of pediatric ALL provides a new attempt for exploring the underlying mechanism and early detection of CNS infiltration in pediatric ALL.
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Molecular dynamics simulation technology relies on Newtonian mechanics to simulate the motion of molecular system of the real system by computer simulation. It has been used in the research of self-assembly processes illustration and macroscopic performance prediction of self-assembly nano-drug delivery systems (NDDS) in recent years, which contributes to the facilitation and accurate design of preparations. In this review, the definitions, catalogues, and the modules of molecular dynamics simulation techniques are introduced, and the current status of their applications are summarized in the acquisition and analysis of microscale information, such as particle size, morphology, the formation of microdomains, and molecule distribution of the self-assembly NDDS and the prediction of their macroscale performances, including stability, drug loading capacity, drug release kinetics and transmembrane properties. Moreover, the existing applications of the molecular dynamic simulation technology in the formulation prediction of self-assembled NDDS were also summarized. It is expected that the new strategies will promote the prediction of NDDS formulation and lay a theoretical foundation for an appropriate approach in NDDS studies and a reference for the wider application of molecular dynamics simulation technology in pharmaceutics.
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Wound healing is a complex process under precise regulation, including multiple stages such as inflammation, anti-inflammatory, and regeneration. Macrophages play an important regulatory role in the differentiated process of wound healing due to their obvious plasticity. If macrophages fail to express specific functions in a timely manner, it will affect the healing function of tissues and lead to pathological tissue healing. Therefore, it is of great significance to understand the different functions of different types of macrophages and to regulate them specifically in different stages of wound healing to promote the healing and regeneration of wound tissue. In this paper, we illustrate the different functions of macrophages in the wound and their basic mechanisms, according to the basic process of wound healing, and emphasize the strategies of macrophage regulation that may be applied to clinical treatment in the future.
Subject(s)
Humans , Inflammation , Macrophages , Wound HealingABSTRACT
The present study aimed to explore the main active components and potential mechanisms of Panax notoginseng saponins(PNS) and osteopractic total flavone(OTF) in the treatment of osteoporosis(OP) through network pharmacology, molecular docking and in vitro cell experiments, which was expected to provide a theoretical basis for clinical applications. The blood-entering components of PNS and OTF were obtained from literature search and online database, and their potential targets were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The OP targets were obtained by means of searching Online Mendelian Inheritance in Man(OMIM) and GeneCards. The common targets of the drug and disease were screened by Venn. Cytoscape was used to construct a "drug-component-target-disease" network, and the core components were screened according to the node degree. The protein-protein interaction(PPI) network of the common targets was constructed by STRING and Cytoscape, and the core targets were screened according to the node degree. GO and KEGG enrichment analysis of potential therapeutic targets were carried out by R language. Molecular docking was used to determine the binding activity of some active components to key targets by AutoDock Vina. Finally, HIF-1 signaling pathway was selected for in vitro experimental verification according to the results of KEGG pathway analysis. Network pharmacology showed that there were 45 active components such as leachianone A, kurarinone, 20(R)-protopanaxatriol, 20(S)-protopanaxatriol, and kaempferol, and 103 therapeutic targets such as IL6, AKT1, TNF, VEGFA and MAPK3 involved. PI3K-AKT, HIF-1, TNF and other signaling pathways were enriched. Molecular docking revealed that the core components had good binding ability to the core targets. In vitro experiments found that PNS-OTF could up-regulate the mRNA expression levels of HIF-1α, VEGFA and Runx2, indicating that the mechanism of PNS-OTF in treating OP may be related to the activation of HIF-1 signaling pathway, and thus PNS-OTF played a role in promoting angiogenesis and osteogenic differentiation. In conclusion, this study predicted the core targets and pathways of PNS-OTF in treating OP based on network pharmacology and carried out in vitro experimental verification, which reflected the characteristics of multi-component, multi-target and multi-pathway synergy of PNS-OTF, and provided new ideas for the future clinical treatment of OP.