ABSTRACT
OBJECTIVE: The knee joint of hemophiliacs may face the result of local morphological changes due to long-term irritation of synovitis. This study aims to elucidate the morphological characteristics of distal femur in hemophilic arthritis (HA) and compare the compatibility of three types of prostheses with the anteroposterior (AP) and mediolateral (ML) dimensions of the femoral osteotomy surface. METHODS: This study retrospectively and randomly selected 50 patients with HA registered for treatment at our hospital from June 2016 to August 2022 as the study subjects, with an equal number of male osteoarthritis (OA) patients and healthy male individuals set as the control group. This study used medical digitalization software to simulate osteotomies on the distal femur during total knee arthroplasties (TKA) for 50 patients with HA, OA patients, and the healthy population, respectively, and measure the morphological parameters to compare with three commonly used femoral components of TKA in clinical practice. The differences between the femur resection of anteroposterior and mediolateral (FRAP, FRML) osteotomy surface and the prosthesis's BOX-AP/ML were compared in three prostheses. One-way ANOVA and multiple Kruskal-Wallis H test were used for the normal or non-normal distribution data, and pairwise comparisons between groups were conducted using the Bonferroni method, and the linear correlation analysis was utilized to assess the relationship between section femoral morphological data and prosthesis parameters. RESULT: In HA patients, the morphological characteristics of the distal femur were shown as shorter than femur AP (FAP), medial and lateral condyle anterior-posterior dimension (FMCAP, FLCAP), notch width (NW), posterolateral condyle height (PLCH), posteromedial condyle width (PMCW), and posterior condylar axis length (PCAL) dimension. They had comparatively smaller femur section aspect ratios (p < 0.005). They showed longer posterolateral condyle width (PLCW), anterior condyle mediolateral dimension (FRACML), anterolateral condyle height (ALCH), and femur resection anterior condylar mediolateral (FRACML) dimension (p < 0.005). They showed larger distal femur aspect ratio and resection aspect ratio (FAR, FRAR, p < 0.005). All selected prostheses showed ML undercoverage under similar AP dimensions, and ML undersizing of Attune systems was more obvious in three femoral prostheses. CONCLUSION: The distal femur morphological change of HA patient is shown as smaller AP dimension, narrow posterior condyle spacing, lower and shallower trochlear, thinner anterior condyle, wider and lower intercondylar notch and higher posterior-lateral condyle. The selected prostheses showed ML undercoverage under similar AP dimensions. This typical morphological tendency of the distal femur seems to warrant consideration in the process of knee joint prosthesis upgrading.
ABSTRACT
Desmoglein-2 (DSG2) is a transmembrane glycoprotein belonging to the desmosomal cadherin family, which mediates cell-cell junctions; regulates cell proliferation, migration, and invasion; and promotes tumor development and metastasis. We previously showed serum DSG2 to be a potential biomarker for the diagnosis of esophageal squamous cell carcinoma (ESCC), although the significance and underlying molecular mechanisms were not identified. Here, we found that DSG2 was increased in ESCC tissues compared with adjacent tissues. In addition, we demonstrated that DSG2 promoted ESCC cell migration and invasion. Furthermore, using interactome analysis, we identified serine/threonine-protein kinase D2 (PRKD2) as a novel DSG2 kinase that mediates the phosphorylation of DSG2 at threonine 730 (T730). Functionally, DSG2 promoted ESCC cell migration and invasion dependent on DSG2-T730 phosphorylation. Mechanistically, DSG2 T730 phosphorylation activated EGFR, Src, AKT, and ERK signaling pathways. In addition, DSG2 and PRKD2 were positively correlated with each other, and the overall survival time of ESCC patients with high DSG2 and PRKD2 was shorter than that of patients with low DSG2 and PRKD2 levels. In summary, PRKD2 is a novel DSG2 kinase, and PRKD2-mediated DSG2 T730 phosphorylation promotes ESCC progression. These findings may facilitate the development of future therapeutic agents that target DSG2 and DSG2 phosphorylation. © 2024 The Pathological Society of Great Britain and Ireland.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Esophageal Squamous Cell Carcinoma/metabolism , Phosphorylation , Protein Kinase D2 , Esophageal Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/physiology , Serine , Cell Movement/physiology , Gene Expression Regulation, Neoplastic , Desmoglein 2/genetics , Desmoglein 2/metabolismABSTRACT
Dislocation is a complication of acetabular fractures involving the posterior wall, but whether dislocation is an absolute factor impacting the short- to medium-term prognosis of the hip joint remains controversial. This study aimed to compare the short- to medium-term clinical and radiological results among patients diagnosed with an acetabular fracture involving the posterior wall, with or without dislocation.Seventy-nine patients diagnosed with an acetabular fracture involving the posterior wall were retrospectively divided into posterior dislocation and non-dislocation groups. All fractures were open reduction + internal fixation with a plate screw combination through the single Kocher-Langenbeck approach. The short- to medium-term radiographic outcomes of follow-up were evaluated using the Matta radiologic grading system, while the clinical outcomes were evaluated using the modified Merle d'Aubigné-Postel evaluation system.The mean follow-up duration for all patients was 43.90 (range 24-75) months. Both groups achieved similar short- to medium-term clinical and radiographic results. There seems to be no significant differences between the two groups regarding the short- to medium-term assessment of clinical and radiographic results and the occurrence of postoperative complications (p > 0.05).In patients with acetabular fractures involving the posterior wall, hip dislocation is probably not an absolute determinant of a poor outcome. Even with early reduction, the short- to medium-term prognosis results appear similar to those of patients without dislocation.
ABSTRACT
AIM: To quantitatively measure ocular morphological parameters of guinea pig with Python technology. METHODS: Thirty-six eyeballs of eighteen 3-week-old guinea pigs were measured with keratometer and photographed to obtain the horizontal, coronal, and sagittal planes respectively. The corresponding photo pixels-actual length ratio was acquired by a proportional scale. The edge coordinates were identified artificially by ginput function. Circle and conic curve fitting were applied to fit the contour of the eyeball in the sagittal, coronal and horizontal view. The curvature, curvature radius, eccentricity, tilt angle, corneal diameter, and binocular separation angle were calculated according to the geometric principles. Next, the eyeballs were removed, canny edge detection was applied to identify the contour of eyeball in vitro. The results were compared between in vivo and in vitro. RESULTS: Regarding the corneal curvature and curvature radius on the horizontal and sagittal planes, no significant differences were observed among results in vivo, in vitro, and the keratometer. The horizontal and vertical binocular separation angles were 130.6°±6.39° and 129.8°±9.58° respectively. For the corneal curvature radius and eccentricity in vivo, significant differences were observed between horizontal and vertical planes. CONCLUSION: The Graphical interface window of Python makes up the deficiency of edge detection, which requires too much definition in Matlab. There are significant differences between guinea pig and human beings, such as exotropic eye position, oblique oval eyeball, and obvious discrepancy of binoculus. This study helps evaluate objectively the ocular morphological parameters of small experimental animals in emmetropization research.
ABSTRACT
Liver ischemia-reperfusion injury (IRI) remains a common issue and with the increasing incidence of Nonalcoholic fatty liver disease (NAFLD), which are more sensitive to IRI, it is crucial to explore the possible strategy to alleviate the steatotic liver IRI. Several modes of cell death are involved in hepatocytes and immune cells during hepatic IRI, and the effects of different cell death inhibitors including apoptosis, necroptosis, pyroptosis, and ferroptosis in steatotic liver IRI have not been investigated. We established 70% IRI model on steatotic liver in mice. Apoptosis, necroptosis, pyroptosis and ferroptosis inhibitors were used to evaluate their effects on liver injury, inflammatory response, and immune cell infiltration. Immunofluorescence and immunohistochemical results demonstrated that there were apoptosis, necroptosis, pyroptosis, and ferroptosis in the progression of IRI in steatotic liver. All four types of cell death inhibitors showed protective effects, but ferroptosis inhibitor Fer-1 and pyroptosis inhibitor VX765 exerted better protective effects compared the apoptosis inhibitor Z-VAD and necroptosis inhibitor Nec-1. Further, we found that pyroptosis occurred mainly in macrophages and ferroptosis occured primarily in hepatocytes during steatotic liver IRI. Ferroptosis in heaptocytes and pyroptosis in macrophages are two major cell death types involved in steatotic liver IRI and inhibiting these cell death exerted good protective effects.
Subject(s)
Non-alcoholic Fatty Liver Disease , Reperfusion Injury , Animals , Mice , Liver/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Hepatocytes/metabolism , Apoptosis , Reperfusion Injury/metabolismABSTRACT
Objective To systematically evaluate the risk factors of contrast medium extravasation(CME).Methods The rele-vant literature on the risk factors of CME were searched from CNKI,WanFang,VIP,CBM,Cochrane Library,ProQuest,PubMed,Ovid,Web of Science,and Embase via computer.Meta-analysis was performed via RevMan5.4.Results A total of 10 articles were included,involving 17 risk factors.The results of the Meta-analysis showed that contrast medium(CM)concentration[odds ratio(OR)=2.02],age(OR=2.22),combined tumor(OR=2.87),puncture site(OR=2.73),nursing experience(OR=2.78),osmotic pressure(OR=3.29),combined circulatory disease(OR=4.56)were the statistically significant factors.Conclusion The independ-ent risk factors of CME include CM concentration,age,combined tumor,puncture site,nursing experience,osmotic pressure,and combined circulatory disease.
ABSTRACT
Objective:To investigate the current situation of occupational burnout among bus drivers in Wuhu City and analyze its influencing factors.Methods:A survey was conducted in 1 388 bus drivers in Wuhu City from Sep to Nov 2022 using the general information questionnaire,the Maslach Burnout Inventory-General Survey(MBI-GS),and the Pittsburgh Sleep Quality Index(PSQI).Multivariable logistic regression analysis was used to analyze the influencing factors of occupational burnout in bus drivers.Spearman correlation analysis was used to analyze the correlation between occupational burnout and sleep quality.Results:Among 1 388 bus drivers,642(46.3%)were positive for occupational burnout,and 139(10.0%)were found to have sleep disorders.Multivariable logistic regression analysis showed that longer bus driving experience(OR=1.873,95%CI:1.325-2.648),lower monthly income(OR=0.376,95%CI:0.158-0.774),higher smoking frequency(OR=1.313,95%CI:1.188-2.163),higher drinking frequency(OR=1.342,95%CI:1.018-1.769),lower weekly physical exercise frequency(OR=0.367,95%CI:0.243-0.555),and poor sleep quality(OR=13.110,95%CI:7.284-23.594)were the influencing factors of bus driver occupational burnout(P<0.05).Spearman correlation analysis showed that the total score of occupational burnout and its dimension scores were positively correlated with the total score of sleep quality and its dimension scores(rs=0.12-0.83,P<0.01).Conclusion:The problem of occupational burnout among bus drivers in Wuhu City is relatively serious,and a part of people have sleep problems,which should be paid great attention to and active measures should be taken in time.
ABSTRACT
BACKGROUND:Clinical treatment for colon cancer mainly includes fluorouracil,irinotecan and oxaliplatin-based therapy.Studies have shown that membrane transport proteins such as ATP-binding cassette transport protein of G2(ABCG2)mediate the transport of these drugs.However,when patients develop resistance to these chemotherapeutic drugs,the high expression of ABCG2 leads to a significant decrease in the therapeutic effect and raises the problem of drug resistance in colon cancer.New drugs and treatments are urgently needed to improve the efficacy.Lycium barbarum polysaccharide has a wide range of biological activities.It can be used as anti-tumor drug to overcome the damage to normal cells in the process of chemotherapy and radiotherapy in tumor patients. OBJECTIVE:To explore the reversal effect of Lycium barbarum polysaccharide in combination with oxaliplatin on colon cancer drug-resistant cells through in vitro experiments to investigate the possible molecular mechanism of Lycium barbarum polysaccharide reversal on colon cancer drug-resistant cells. METHODS:Colon cancer cell line HCT116 and oxaliplatin-resistant cell line HCT116-OXR were selected for in vitro experiments.The optimal intervention concentration and intervention time of Lycium barbarum polysaccharide and oxaliplatin were determined by CCK8 assay of cell proliferation.Samples were further divided into the HCT116 control group,HCT116-OXR blank treatment group,Lycium barbarum polysaccharide group(2.5 mg/mL Lycium barbarum polysaccharide),and oxaliplatin group(10 μmol/L oxaliplatin),and Lycium barbarum polysaccharide + oxaliplatin group(2.5 mg/mL Lycium barbarum polysaccharide +10 μmol/L oxaliplatin).Cell apoptosis was detected by flow cytometry.The protein expression levels of phosphomannose isomerase(PMI)and ABCG2 were detected by immunofluorescence and western blot assay.Phosphatidylinositol3-kinase(PI3K),protein kinase B(AKT),B-cell lymphoma 2(Bcl-2)and BCL2-Associated X(Bax)were detected by western blot assay. RESULTS AND CONCLUSION:(1)HCT116-OXR was more sensitive to Lycium barbarum polysaccharide compared to HCT116(P<0.05).(2)Compared with the HCT116-OXR blank group,Lycium barbarum polysaccharide + oxaliplatin could promote apoptosis of HCT116-OXR cells(P<0.05).The protein expression of Bcl-2 was significantly down-regulated(P<0.05);the protein expression of Bax was significantly up-regulated(P<0.05);the protein expression of ABCG2,PMI,PI3K and AKT was significantly down-regulated(P<0.05).(3)These results indicate that Lycium barbarum polysaccharide reverses drug resistance in colon cancer by inhibiting PMI/PI3K/AKT signaling pathway,which lays the foundation for studying the molecular mechanism of Lycium barbarum polysaccharide's sensitizing chemotherapeutic effects.
ABSTRACT
Objective:To explore the application effect of 5A self-management support method in the management of patients with stroke.Methods:A 5A self-management support program for stroke patients was developed from the five dimensions of Ask,Advice,Assess,Assist and Arrange.A total of 75 stroke patients admitted to the Neurology Department of Beijing Shijitan Hospital from November 2020 to April 2021 were randomly selected and divided into a control group(38 cases)and an observation group(37 cases)according to different intervention methods.The control group adopted routine intervention method,the observation group adopted 5A self-management support method.The intervention time expired 3 months after the patient was discharged.The intervention effects of the two groups were evaluated from the scores of self-management behavior,self-efficacy,activities of daily living and depression and anxiety situation.Results:At the end of the third month after discharge,the self-management behavior and self-efficacy scores for weekly exercise time,cognitive symptom management,communication with doctors,symptom management self-efficacy and disease common management self-efficacy scores of patients in the observation group scored(180.92±102.38),(3.68±1.32),(3.29±1.41),(7.15±3.44)and(6.82±2.10),respectively,which were significantly higher than those of the control group,the differences were statistically significant(t=5.63,4.10,4.37,6.40,7.60,P<0.05).At the end of the third month after discharge,the modified Barthel index(MBI)score of the patients in the observation group was(68.06±12.80),which was significantly higher than that of control group,the difference was statistically significant(t=7.27,P<0.05);the depression and anxiety scores of patients in the observation group were lower than those of the control group,the difference was statistically significant(t=2.38,2.64,P<0.05).Conclusion:The 5A self-management support method can significantly improve the self-management behavior and the ability of daily living activities of stroke patients after discharge,and effectively improve the anxiety and depression of patients,and improve the self-management effect of stroke patients after discharge.
ABSTRACT
Objective:To analyze the clinical features of MDA5 antibody positive dermatomyositis (MDA5-DM) and to provide evidence for early diagnosis and treatment.Methods:From March 2019 to June 2021, 272 patients with anti-MDA5-DM from the Nanjing Medical University myositis-associated interstitial lung disease cohort were enrolled, with 76 patients with anti-synthetase syndrome (ASS) as the control group. The clinical characteristics and the occurrence of interstitial lung disease were analyzed. T-test was used for normally distributed and variance-homogeneous independent samples, Mann-Whitney U test for non-normally distributed data, and chi-square test or Fisher′s exact test for dichotomous variables. Results:Among the 272 anti-MDA5-DM patients, 88.6% (241/272) developed interstitial lung disease (ILD), and 33.8% (92/272) developed rapidly progressive ILD (RP-ILD). The six-month all-cause mortality rate of anti-MDA5-DM patients was 16.9% (46/272), and it was as high as 47.8% (44/92) for those with RP-ILD. Compared with ASS patients, anti-MDA5-DM patients had a significantly higher proportion of males, arthritis, Gottron's sign, heliotrope rash, V-sign, periungual erythema, and skin ulcers ( P<0.05). The levels of ALT, AST, and ferritin were significantly increased ( P<0.05). Compared with non-RP-ILD patients, RP-ILD patients had a significantly higher proportion of males [35.9%(33/92) vs. 23.3%(42/180), χ2=4.79, P=0.029], higher levels of LDH [387 (276, 547) U/L vs. 310 (245, 400) U/L, Z=-3.67, P<0.001], ESR [45.5 (29.25, 63.25) mm/1 h vs. 31.2 (20, 51) mm/1 h, Z=-3.71, P<0.001], CRP [10.9 (4.1, 25.2) mg/L vs. 4.54 (2.58, 9.08) mg/L, Z=-4.97, P<0.001], ferritin [1 340 (650, 2 000) ng/ml vs. 556 (203, 1 186) ng/ml, Z=-4.40, P<0.001], and a higher proportion of anti-Ro52 antibody and anti-MDA5 antibody co-positivity [87.0%(80/92) vs. 52.2%(94/180), χ2=31.87, P<0.001]. Conclusion:Anti-MDA5-DM patients are prone to develop RP-ILD and have poor prognosis.
ABSTRACT
Objective To analyze the clinicopathological characteristics and prognosis of oligodendroglioma with IDH mutation and 1p/19q codeletion. Methods We collected the data of 54 oligodendroglioma patients with IDH mutation and 1p/19q codeletion.The patients'clinicopathological data, including age, histological grade, and tumor site, were analyzed for the effects on progression-free and overall survival. Results Among the 54 patients, 46 cases were with tumor sites in one lobe, and eight cases involved tumor sites in more than two lobes.A total of 12 and 42 cases had WHO grades 2 and 3 oligodendroglioma, respectively.Detection by fluorescence in situ hybridization showed 1p/19q co-deletion in all cases.Immunohistochemical tests revealed diffuse and strong positive results for Olig2.All glial fibrillary acidic proteins were positive.p53 was strongly positive in six cases.ATRX was expressed in all 48 cases.Ki-67 proliferation index ranged from 5% to 60%.Sanger sequencing showed that all 54 cases had IDH gene mutations (40 cases were IDH1 mutations, and 14 were IDH2 mutations), and 33 cases had telomerase reverse transcriptase promoter mutations.Relapse and metastasis occurred in 16 patients during treatment.Univariate analysis indicated that the postoperative recurrence and metastasis interval of more than two years can prolong the progression-free and overall survival of patients.All 54 patients had a mean progression-free survival of 33.5 months and the mean overall survival of 40.7 months. Conclusion For oligodendroglioma with IDH mutation and 1p/19q codeletion, precision chemoradiotherapy after surgery can reduce the risk of progression, and the postoperative recurrence and metastasis interval is associated with the prognosis.
ABSTRACT
The objective of this study was to analyze the effects on cell viability, apoptosis, and cell cycle of non-small cell lung cancer (NSCLC) A549 cells after intervention with Agrimonia pilosa (AP) and investigate Agrimonia pilosa anti-tumor activity in vitro. Meanwhile, liquid chromatography mass spectrometry (LC-MS) metabolomics technology was used to analyze the changes of cellular metabolites and metabolic pathways. The results of this study will provide a theoretical and experimental basis for investigating the mechanism of the effect of Agrimonia pilosa on non-small cell lung cancer A549 cells. The results showed that the cell nucleus of A549 cells crumpled and apoptosis occurred with the increase of drug concentration. The survival rate of the cells decreased, and the inhibition rate reached 21.5% and 91.74% under the low and high dose conditions, respectively. Lactate dehydrogenase (LDH) content increased (P < 0.05). Metabolomics results showed significant differences in metabolism between groups, thirty-three distinct metabolites including LysoPC(24:0/0:0), LysoPC(17:0/0:0) and PC(O-40:5) were deduced. The pathway enrichment showed that the Agrimonia pilosa plays an anti-tumor role mainly by regulating the metabolism of glycerophosphate and purine in A549 cells, in which the effect on glycerophosphate metabolism pathway was most significant. The results of combined pharmacodynamics suggested that Agrimonia pilosa might induce apoptosis and inhibit the growth of A549 cells by regulating LysoPC(24:0/0:0), LysoPC(17:0/0:0) and PC(O-40:5) metabolites in A549 cells.
ABSTRACT
Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.
ABSTRACT
OBJECTIVE@#To compare the role and importance of fibular fixation in tibiofibular fractures by Meta-analysis.@*METHODS@#The literature related to the comparison of the efficacy of fixation of the fibula with or without fixation on the treatment of tibiofibular fractures was searched through the databases of China Knowledge Network, Wipu, Wanfang, The Cochrane Library, Web of science and Pubmed, and statistical analysis was performed using RevMan 5.3 software. The rates of malrotation, rotational deformity, internal/external deformity, anterior/posterior deformity, non-union, infection, secondary surgery and operative time were compared between the fibula fixation and non-fixation groups.@*RESULTS@#A total of 11 publications were included, six randomised controlled trials and five case-control trials, eight of which were of high quality. A total of 813 cases were included, of which 383 were treated with fibula fixation and 430 with unfixed fibulae.Meta-analysis results showed that fixation of the fibulae in the treatment of tibiofibular fractures reduced the rates of postoperative rotational deformity[RR=0.22, 95%CI(0.10, 0.45), P<0.000 1] and internal/external deformity[RR=0.34, 95%CI(0.14, 0.84), P=0.02] and promoted fracture healing [RR=0.76, 95%CI(0.58, 0.99), P=0.04]. In contrast, the rates of poor reduction [RR=0.48, 95% CI(0.10, 2.33), P=0.36], anterior/posterior deformity[RR=1.50, 95%CI(0.76, 2.96), P=0.24], infection[RR=1.43, 95%CI(0.76, 2.72), P=0.27], secondary surgery[RR=1.32, 95%CI(0.82, 2.11), P=0.25], and operative time[MD=10.21, 95%CI(-17.79, 38.21), P=0.47] were not statistically significant (P>0.05) for comparison.@*CONCLUSION@#Simultaneous fixation of the tibia and fibula is clinically more effective in the treatment of tibiofibular fractures.
Subject(s)
Humans , Fibula/surgery , Fractures, Bone/complications , Tibia/surgery , Fracture Healing , Fracture Fixation, Internal , Treatment OutcomeABSTRACT
In the tumor microenvironment, metabolic reprogramming can impact metabolic characteristics of T cells, thus inducing immunosuppression to promote tumor immune escape. The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in regulating diverse functions of various immune cells. This review mainly focuses on the molecular mechanism of mTOR signaling in regulating cellular energy metabolism process, and the activation status of mTOR signaling under different nutritional environments. In addition, it also summarizes the role of the mTOR signaling in regulatory T cell (Tregs) metabolism and function in current studies, and evaluates the potential of mTOR as a clinical immunotherapeutic target and its current application challenges.
Subject(s)
Humans , Immunosuppression Therapy , Metabolic Reprogramming , Signal Transduction , Sirolimus , T-Lymphocytes, Regulatory , TOR Serine-Threonine KinasesABSTRACT
Objective: To explore the association between the intake and changes in various types of food and the changes in blood pressure in patients with mild to moderate hypertension. Methods: Mild to moderate hypertension participants with complete baseline and outcome data were included from DECIDE-Diet study, a multicenter, randomized controlled trial. Dietary records and blood pressure measurements at both 7-day run-in (baseline) and 28-day intervention phases were collected for enrolled participants. Blood pressure change was defined as the difference between blood pressure at the end of trial and the baseline blood pressure. Baseline intake of food was the average daily intake during the run-in period, and the intake increment was defined as the difference between the average intake during the trial period and the average intake during the run-in period. After adjusting for age, sex, study center, intervention groups, baseline body mass index (kg/m2), antihypertension medication use, and baseline total calorie intake, a linear regression model was used to analyze the associations of the before-after-intervention change in blood pressure with baseline intake and intake increment of foods. Results: A total of 258 patients with mild to moderate hypertension were included, including 133 males, aged (56.5±9.9) years. (1) After adjusting for confounding factors, there was no significant association between baseline intake of food and baseline blood pressure (all P>0.05). The blood pressure change was negatively associated with baseline intakes of tubers, vegetables, and vegetable oils but positively with baseline intake of meats; and was negatively associated with intake increment of whole grains and fish (all P<0.05). (2) The multiple linear regression analysis showed that baseline intake of vegetables (β=-0.021, P=0.004), vegetable oils (β=-0.260, P=0.002), and increment in intake of fish (β=-0.128, P=0.026) were all significantly associated with changes in systolic blood pressure; baseline intake of vegetables (β=-0.017, P=0.002), vegetable oils (β=-0.182, P=0.001), dairy products (β=0.021, P=0.022), and increment in intake of fish (β=-0.092, P=0.010) were all significantly associated with changes in diastolic blood pressure. Conclusion: Increasing the intake of whole grains, vegetables, vegetable oils, and fish and decreasing the intake of meat may be beneficial for blood pressure control in patients with mild to moderate hypertension.
Subject(s)
Male , Adult , Animals , Humans , Blood Pressure , Fruit , Diet , Hypertension , Vegetables , Plant OilsABSTRACT
Objective: To explore the feasibility of using two-dimensional speckle tracking echocardiography for measuring right ventricular strain and function in healthy adults, and to analyze the impact of age and gender. Methods: This study is a cross-sectional study. Healthy adults who underwent physical examination in the Physical Examination Center of Beijing Hospital from January 1, 2020 to January 1, 2021 were included. Two researchers independently measured various right ventricular longitudinal strain indices using the Echopac software, including (global longitudinal strain (GLS), apical longitudinal strain (ALS), midventricle longitudinal strain (MLS), basal longitudinal strain (BLS), free wall GLS (FWGLS), free wall ALS (FWALS), free wall MLS (FWMLS) and free wall BLS (FWBLS)) as well as tricuspid annular plane systolic excursion (TAPSE) and right ventricle-fraction of area change (RVFAC). The above indicators were taken as the average of two physicians. The consistency of the measurements by two physicians was evaluated by the within-group correlation coefficient (ICC). Results: A total of 233 subjects were included, including 137 males, aged (58.5±14.2) years. ICC values was all above 0.8 with excellent agreement. The values of FWGLS and GLS in healthy adults were -26.63% and -21.89%, respectively. There was no statistically significant difference in TAPSE ((2.06±0.41)cm vs. (2.10±0.39)cm, P=0.510) and RVFAC ((51.17±9.91)% vs. (50.89±8.65)%, P=0.826) between males and females. The values of various right ventricular long axis strain indicators (GLS, ALS, MLS, BLS, FWGLS, FWMLS, FWMLS, FWBLS) in females aged 18 to 40 and 41 to 65 years were higher than those in males of the same age (all P<0.05), while there was no statistically significant difference in the values of various right ventricular long axis strain indicators between the sexes in subjects aged 65 years and above (all P>0.05). In females, the right ventricular GLS, ALS, MLS, FWGLS, FWALS, FWMLS, and FWBLS values in the groups aged 18 to 40 and 41 to 65 years were significantly higher than those in the group aged 65 years and above (all P<0.05). In contrast, no significant differences were found in these indices among different age groups in males (all P>0.05). Conclusions: Using two-dimensional speckle tracking technology in echocardiography to measure right ventricular strain indicators is feasible and highly reproducible. Gender and age have an impact on right ventricular strain indicators.
Subject(s)
Adult , Male , Female , Humans , Ventricular Function, Right , Cross-Sectional Studies , Amyotrophic Lateral Sclerosis , Echocardiography/methods , Heart Ventricles/diagnostic imaging , Ventricular Dysfunction, RightABSTRACT
Objective: To explore the association between the intake and changes in various types of food and the changes in blood pressure in patients with mild to moderate hypertension. Methods: Mild to moderate hypertension participants with complete baseline and outcome data were included from DECIDE-Diet study, a multicenter, randomized controlled trial. Dietary records and blood pressure measurements at both 7-day run-in (baseline) and 28-day intervention phases were collected for enrolled participants. Blood pressure change was defined as the difference between blood pressure at the end of trial and the baseline blood pressure. Baseline intake of food was the average daily intake during the run-in period, and the intake increment was defined as the difference between the average intake during the trial period and the average intake during the run-in period. After adjusting for age, sex, study center, intervention groups, baseline body mass index (kg/m2), antihypertension medication use, and baseline total calorie intake, a linear regression model was used to analyze the associations of the before-after-intervention change in blood pressure with baseline intake and intake increment of foods. Results: A total of 258 patients with mild to moderate hypertension were included, including 133 males, aged (56.5±9.9) years. (1) After adjusting for confounding factors, there was no significant association between baseline intake of food and baseline blood pressure (all P>0.05). The blood pressure change was negatively associated with baseline intakes of tubers, vegetables, and vegetable oils but positively with baseline intake of meats; and was negatively associated with intake increment of whole grains and fish (all P<0.05). (2) The multiple linear regression analysis showed that baseline intake of vegetables (β=-0.021, P=0.004), vegetable oils (β=-0.260, P=0.002), and increment in intake of fish (β=-0.128, P=0.026) were all significantly associated with changes in systolic blood pressure; baseline intake of vegetables (β=-0.017, P=0.002), vegetable oils (β=-0.182, P=0.001), dairy products (β=0.021, P=0.022), and increment in intake of fish (β=-0.092, P=0.010) were all significantly associated with changes in diastolic blood pressure. Conclusion: Increasing the intake of whole grains, vegetables, vegetable oils, and fish and decreasing the intake of meat may be beneficial for blood pressure control in patients with mild to moderate hypertension.
Subject(s)
Male , Adult , Animals , Humans , Blood Pressure , Fruit , Diet , Hypertension , Vegetables , Plant OilsABSTRACT
Objective: To explore the feasibility of using two-dimensional speckle tracking echocardiography for measuring right ventricular strain and function in healthy adults, and to analyze the impact of age and gender. Methods: This study is a cross-sectional study. Healthy adults who underwent physical examination in the Physical Examination Center of Beijing Hospital from January 1, 2020 to January 1, 2021 were included. Two researchers independently measured various right ventricular longitudinal strain indices using the Echopac software, including (global longitudinal strain (GLS), apical longitudinal strain (ALS), midventricle longitudinal strain (MLS), basal longitudinal strain (BLS), free wall GLS (FWGLS), free wall ALS (FWALS), free wall MLS (FWMLS) and free wall BLS (FWBLS)) as well as tricuspid annular plane systolic excursion (TAPSE) and right ventricle-fraction of area change (RVFAC). The above indicators were taken as the average of two physicians. The consistency of the measurements by two physicians was evaluated by the within-group correlation coefficient (ICC). Results: A total of 233 subjects were included, including 137 males, aged (58.5±14.2) years. ICC values was all above 0.8 with excellent agreement. The values of FWGLS and GLS in healthy adults were -26.63% and -21.89%, respectively. There was no statistically significant difference in TAPSE ((2.06±0.41)cm vs. (2.10±0.39)cm, P=0.510) and RVFAC ((51.17±9.91)% vs. (50.89±8.65)%, P=0.826) between males and females. The values of various right ventricular long axis strain indicators (GLS, ALS, MLS, BLS, FWGLS, FWMLS, FWMLS, FWBLS) in females aged 18 to 40 and 41 to 65 years were higher than those in males of the same age (all P<0.05), while there was no statistically significant difference in the values of various right ventricular long axis strain indicators between the sexes in subjects aged 65 years and above (all P>0.05). In females, the right ventricular GLS, ALS, MLS, FWGLS, FWALS, FWMLS, and FWBLS values in the groups aged 18 to 40 and 41 to 65 years were significantly higher than those in the group aged 65 years and above (all P<0.05). In contrast, no significant differences were found in these indices among different age groups in males (all P>0.05). Conclusions: Using two-dimensional speckle tracking technology in echocardiography to measure right ventricular strain indicators is feasible and highly reproducible. Gender and age have an impact on right ventricular strain indicators.
Subject(s)
Adult , Male , Female , Humans , Ventricular Function, Right , Cross-Sectional Studies , Amyotrophic Lateral Sclerosis , Echocardiography/methods , Heart Ventricles/diagnostic imaging , Ventricular Dysfunction, RightABSTRACT
OBJECTIVE@#To assess the effectiveness and feasibility of carrier detection for Spinal muscular atrophy (SMA) by using digital PCR assay.@*METHODS@#Peripheral blood samples were collected from 214 pregnant women who were routinely screened for SMA carriers, of which 204 were randomly selected samples and 10 were samples with known copy numbers of SMN1 exons 7 and 8. Samples with known copy numbers of SMN1 exons 7 and 8 were randomly mixed into the experiment to validate the performance of the digital PCR assay.@*RESULTS@#The copy numbers of SMN1 exons 7 and 8 and SMN2 exons 7 and 8 in peripheral blood samples were detected by digital PCR assay. The results of SMN1 exons 7 and 8 were compared with those of the quantitative PCR method to assess the reliability and clinical performance of the digital PCR assay. Among the 204 random samples, digital PCR has detected five samples with simultaneous heterozygous deletion of SMN1 exons 7 and 8, three samples with heterozygous deletion of SMN1 exon 8 only, and 196 samples with no deletion of SMN1 exons 7 and 8. Ten samples with known SMN1 exons 7 and 8 copy numbers were detected with the expected values. The digital PCR test results were fully consistent with that of the quantitative PCR.@*CONCLUSION@#The results of digital PCR for the detection of copy number variation of SMN1 exons 7 and 8 were consistent with qPCR. Digital PCR assay was able to clearly distinguish the copy number of the target genes, therefore can be used for SMA carrier screening. Moreover, it can also detect copy number of SMN2 exons 7 and 8, which can provide more information for genetic counseling.