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Objective To explore the differentially expressed mRNAs and related biological processes and pathways in fractional low-dose ionizing radiation (LDIR)-induced senescence of normal human bronchial epithelial (HBE) cells by high-throughput mRNA sequencing and bioinformatics techniques. Methods Senescence-associated β-galactosidase staining and senescence-associated secretion phenotype gene mRNA and protein expression levels were measured at 24 and 48 h after irradiating HBE cells 7 times at doses of 0, 50, 100, and 200 mGy, respectively. The differentially expressed genes were screened by high-throughput sequencing for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results The senescence-positive area of fractional low-dose irradiated HBE cells increased in a dose-dependent manner (P < 0.05). The mRNA levels and protein expression of transforming growth factor-β1(TGF-β1) and matrix metalloproteinase-9(MMP-9) genes were increased in the 100 mGy × 7 and 200 mGy × 7 groups at 24 and 48 h after the end of irradiation compared with the control group. High-throughput sequencing showed that there were 882, 475, and 1205 differentially expressed mRNAs in each dose group compared with the control group. GO analysis showed that the differentially expressed mRNAs in each dose group were mainly enriched in biological processes such as cell cycle regulation, regulation of nitrogen compound metabolic process, regulation of cell division and response to stimulus. KEGG analysis showed that the differentially expressed mRNAs were mainly enriched in the pathways of cell cycle, cell senescence, and ferroptosis. Conclusion Fractional LDIR induced senescence in HBE cells, and differentially expressed mRNA-associated biological processes and pathways in senescent cells are related to cell cycle and cell senescence.
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Objective To explore the differences of regional homogeneity(ReHo)between overweight and normal weight male patients with type 2 diabetes mellitus(T2DM)during rest and their correlations with clinical features.Methods Twenty-five untreated male overweight T2DM(OW-T2DM)patients,25 untreated male normal weight T2DM(NW-T2DM)patients and 25 healthy controls(HC)were enrolled.The brain structure and resting-state functional magnetic resonance imaging(rs-fMRI)data were collected from all subjects.The brain structure and rs-fMRI data were preprocessed,and ReHo values of all brain regions were calculated for all subjects.ReHo values were compared among three groups and between groups respectively via the methods of one-way analysis of variance and two-sample t-test.To address the problem of multiple comparisons,the method of AlphaSim was performed(the threshold was set at P<0.005,the number of voxel clusters was>12).In addition,Pearson correlation analysis was performed to explore the relationships between ReHo values of the abnormal brain regions and clinical features in patients.Results(1)The brain regions showed differences of ReHo values among three groups were mainly distributed in the right hemisphere,including the superior parietal gyrus,superior marginal gyrus and superior occipital gyrus;(2)Compared with HC,NW-T2DM patients showed significantly decreased ReHo values in the right medial superior frontal gyrus,right middle cingulate gyrus and left anterior cingulate gyrus;(3)Compared with HC,OW-T2DM patients showed significantly decreased ReHo values in the bilateral postcentral gyrus and bilateral middle cingulate gyrus;(4)Compared with NW-T2DM patients,OW-T2DM patients showed significantly decreased ReHo values in the right superior parietal gyrus,right superior occipital gyrus and left cuneus;(5)ReHo values of the right medial superior frontal gyrus and right superior parietal gyrus were negatively correlated with hemoglobinA1c(HbA1c)level and body mass index(BMI),respectively,in all patients.Conclusion The occurrence of T2DM in male patients may lead to the declined activity of brain regions located in the default mode network(DMN),while overweight may further lead to decreased brain activity within the attention and visual recognition network in male T2DM patients.
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Objective To investigate the feasibility of energy spectrum CT material separation technology for quantitative evaluation of nonalcoholic fatty liver patients,to compare the accuracy of this method with the conventional liver/spleen CT ratio for grading liver fat content.Methods Sixty patients diagnosed with nonalcoholic fatty liver and 20 healthy volunteers were chosen to undergo liver MR multi-echo(ME)Dixon and energy spectrum CT scans.The proton density fat fraction(PDFF),fat concentration(FC),and liver/spleen CT ratio were then measured for each participant.According to PDFF,nonalcoholic fatty liver patients were divided into mild fatty liver group,moderate fatty liver group,and severe fatty liver group.Results With the increase in PDFF,FC increased and the liver/spleen CT ratio decreased.The difference between FC groups in normal,mild,moderate and severe fatty liver groups was statistically significant(P<0.05),while the difference between the liver/spleen CT ratio of normal group and mild fatty liver group was not statistically significant(P>0.05).The receiver operating characteristic(ROC)curve analysis showed that when the critical value of FC was 351.19 mg/mL,the sensitivity,specificity and area under the curve for normal group and fatty liver group were 0.95,0.1 and 0.99,respectively.Conclusion The energy spectrum CT material separation technology has a good correlation between the fat content measured by the MR ME Dixon,which is superior to the fat content measured by the liver/spleen CT ratio.For patients with nonalcoholic fatty liver,FC in energy spectrum CT has high accuracy in differentiating normal and mild fatty liver.
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Objective To investigate the expression of WD repeat-containing protein 5(WDR5)in cervical cancer tissue and its relationship with clinical pathological characteristics and prognosis of patients.Methods 105 CA patients admitted to our hospital from January 2018 to March 2020 were included as the study subjects,the cancer tissue and adjacent tissue samples of patients were collected,Immunohistochemical staining and Western blot were used to detect the level of WDR5 in CA tissue and adjacent cancer tissues.Immunohistochemistry and Western blot were used to determine the level;Survival analysis was conducted using the Kaplan Meier method;The influencing factors of patient prognosis were analyzed through Cox regression.Results Among 105 CA tissue samples,the positive expression rate of WDR5(WDR5 positive cases/total cancer tissue cases)was 68.57% (72/105),which was higher than 22.86% (24/105)in adjacent cancer tissues(P<0.05);Compared to adjacent tissues(1.00±0.11),the expression level of WDR5 was higher in CA tissues(4.66±0.98)(t = 38.030,P<0.05).The expression level of WDR5 is related to the degree of differentiation,TNM staging,and lymph node metastasis(P<0.05);The survival rate of WDR5 positive expression was 65.28% (47/72)lower than that of negative expression of 90.91% (30/33)(Log rank χ2 = 6.732,P = 0.009);TNM staging,WDR5,degree of dif-ferentiation,and lymph node metastasis are all influencing factors for patient prognosis(P<0.05).Conclusion The expression of WDR5 is elevated in cervical cancer tissues,and its changes are closely related to TNM staging,differentiation,lymph node metastasis,and prognosis in cervical cancer patients.
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BACKGROUND:The incidence of high lumbar disc herniation in elderly patients with osteoporosis is increasing.The changes in lumbar overall mechanical strength and biomechanical properties of adjacent vertebrae after conventional posterior approach decompression and interbody fusion have not been clarified.Finite element analysis has great value in the field of biomechanics because of its advantages of non-invasiveness,high repeatability and accuracy. OBJECTIVE:To explore the establishment of a finite element model of senile osteoporotic L3/4 lamina decompression using finite element analysis and intervertebral fusion spine,and to evaluate the biomechanical status of the internal fixation complex of bones under bending motion in elderly patients with osteoporosis. METHODS:Mimics 21.0 was used to extract the DICOM data of the spine CT to establish the 3D bony structure of the lumbar spine(T12-L5),which was imported into Geomagic wrap 2017.The L3/4 full lamina decompression model was established after redrawing the mesh,deleting the nails,cutting the model,filling the cavity,detecting and editing the contour line,constructing curved surfaces and grids,fitting curved surfaces and other operations.Solidworks 2017 was used to construct pedicle screws,connecting rods,and intervertebral fusion cages,which were assembled into the L3/4 full lamina decompression model.Intervertebral discs and articular process cartilage and other structures were established through operations such as stretching,isometric surfaces,moving and copying entities.ANSYS Workbench 17.0 was utilized for material assignment,simulating spinal ligaments,meshing,applying force and limiting boundary conditions.A complete osteoporotic L3/4 laminar decompression and intervertebral fusion spine finite element model was established.The stress,strain and displacement cloud diagram of the L3/4 lamina decompression and intervertebral fusion full lumbar spine finite element model were observed under simulated bending conditions. RESULTS AND CONCLUSION:(1)In terms of the stress cloud diagram:The T12-L1 vertebra had the highest average stress value;L2 dropped by 24%;L3 dropped by 55%,and L4-5 dropped by about 80%.The stress concentration in the L4/5 articular process area was the highest,followed by L2/3,and lighter in L1/2 and T12/L1.The stress concentration at the junction of the screw and the connecting rod was obvious,followed by the screw at the entrance and exit of the pedicle.(2)In terms of strain and displacement cloud map:The strain degree of L4/5 and L2/3 articular process was the highest;the strain degree of T12/L1 and L1/2 was the second,and the L3/4 segmental fusion cage,pedicle screw and connecting rod had no any visible deformation.The intervertebral discs of all segments showed great deformation.(3)It is concluded that the cooperative operation of multiple software can successfully construct a finite element model of the spine with L3/4 lamina decompression and intervertebral fusion in elderly patients with osteoporosis.Elderly patients after lumbar spine surgery can tolerate forward flexion,confirming that L3/4 laminar decompression and intervertebral fusion can maintain the shape of the spine and ensure the stability of the spine,but it is necessary to be alert to the occurrence of thoracolumbar stress fractures and adjacent spondylopathy.
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BACKGROUND:Obesity and its relevant chronic inflammation are important risk factors for inducing type 2 diabetes.This inflammatory response will further involve skeletal muscle,leading to an increase in catabolic and autophagic fluxes in skeletal muscle.Aerobic exercise is the mainstream mode of exercise in the prevention and treatment of type 2 diabetes,and may also has a certain protective effect on skeletal muscle. OBJECTIVE:To explore the effects and regulatory mechanisms of aerobic exercise on glucolipid metabolism,skeletal muscle inflammation and autophagy in type 2 diabetic rats. METHODS:Animal models of type 2 diabetes were established in rats by 8-week high-fat feeding combined with streptozotocin injection,and the experimental rats were then divided into normal control group,normal exercise group,diabetic control group and diabetic exercise group.The exercise group performed 4 weeks of aerobic exercise(16 m/min,60 min/d,5 d/wk).The levels of blood glucose,high-density lipoprotein,low-density lipoprotein and triglyceride in serum were measured by an automated biochemical analyzer.Serum insulin level was determined using enzyme-linked immunosorbent assay and the insulin resistance index and area under the glucose metabolism curve were calculated.The levels of interleukin 6 and tumor necrosis factor α in skeletal muscle were measured by enzyme-linked immunosorbent assay after 4 weeks of aerobic exercise,and the expression levels of forkhead box protein O3(FoxO3),LC3 and p62 in skeletal muscle were measured by western blot assay. RESULTS AND CONCLUSION:The area under the glucose tolerance curve and insulin resistance index both increased significantly in type 2 diabetic rats(P<0.001,P=0.025),and aerobic exercise significantly reduced the area under the glucose tolerance curve and insulin resistance index in the normal exercise group(P<0.001,P=0.038)and diabetic exercise group(P<0.001,P=0.004).Serum high-density lipoprotein significantly decreased(P=0.030),and low-density lipoprotein and triglyceride(P=0.027,P=0.014)levels significantly increased in the diabetic control group compared with the normal control group.Aerobic exercise significantly reduced triglyceride and low-density lipoprotein levels in the normal exercise group(P=0.019,P=0.008)as well as triglyceride levels in the diabetic exercise group(P=0.022).Both interleukin-6 and tumor necrosis factor α levels were significantly increased in the skeletal muscle of type 2 diabetic rats compared with the normal control group(P<0.001,P=0.007),and aerobic exercise significantly reduced tumor necrosis factor α levels in the diabetic exercise group(P=0.017).The LC3-Ⅱ/LC3-I was significantly increased in the skeletal muscle of type 2 diabetic rats compared with the normal control group.Aerobic exercise significantly increased the LC3-Ⅱ/LC3-I in the normal exercise group(P<0.001)and decreased the LC3-Ⅱ/LC3-I,FoxO3 and p62 protein expression levels in the diabetic exercise group(P=0.026,P=0.050,P=0.048).To conclusion,type 2 diabetes model established by high-fat feeding combined with streptozotocin injection has obvious glycolipid metabolism disorder,and leads to inflammatory response and excessive activation of autophagy in skeletal muscle.Aerobic exercise can improve glycolipid metabolism,reduce local inflammation in skeletal muscle and inhibit autophagy,and finally play a protective role in skeletal muscle.
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BACKGROUND:Stem cell therapy is an alternative treatment strategy for restoring damaged myocardial tissue after acute myocardial infarction.Exercise preconditioning can induce endogenous cardioprotective effects in the body.However,the efficacy and mechanism of the combined application are still unclear. OBJECTIVE:To explore the effect and possible mechanism of exercise preconditioning combined with bone marrow mesenchymal stem cells on the therapeutic effect in rats with acute myocardial infarction. METHODS:Seventy male SD rats were randomly divided into sham operation group,model group,stem cell therapy group,exercise preconditioning group,and combined intervention group.Rats in the exercise preconditioning group and combined intervention group underwent 8-week aerobic exercise on the treadmill before modeling.The animal model of acute myocardial infarction was made by ligating the anterior descending coronary artery.The stem cell therapy group and the combined intervention group were injected with bone marrow mesenchymal stem cells(1×109 L-1,1 mL)through the tail vein the next day after modeling.After 4 weeks of treatment,the exercise performance was evaluated by a graded treadmill exercise test.The cardiac structure and function were detected by echocardiography.The left ventricle was isolated.2,3,5-Triphenyltetrazolium chloride staining was used to evaluate myocardial infarct size.Masson staining was used to obtain collagen volume fraction.CD31 immunohistochemical staining was used to detect myocardial capillary density.TUNEL staining was used to detect myocardial cell apoptosis.Immunoblotting was used to detect protein expression levels of stromal cell-derived factor 1,CXC chemokine receptor protein 4,tumor necrosis factor-α,interleukin-10,and vascular endothelial growth factor. RESULTS AND CONCLUSION:(1)Intervention efficacy:Compared with the sham operation group,exercise performance,left ventricular ejection fraction,left ventricular fractional shortening,and CD31 positive cell rate decreased(P<0.05);myocardial infarct size,collagen volume fraction,and myocardial apoptotic rate increased(P<0.05)in the model group.Compared with the model group,exercise performance was not statistically significant(P>0.05)in the stem cell therapy group,and the exercise performance improved(P<0.05)in the exercise preconditioning and combined intervention groups;left ventricular ejection fraction,left ventricular fractional shortening,and CD31 positive cell rate increased(P<0.05),and the myocardial infarct size,collagen volume fraction,and cardiomyocyte apoptosis rate decreased(P<0.05)in the stem cell therapy,exercise preconditioning,and combined intervention groups.Compared with the stem cell therapy group,exercise performance,left ventricular ejection fraction,left ventricular shortening fraction,and CD31 positive cell rate increased(P<0.05),myocardial infarct size,collagen volume fraction,and myocardial cell apoptosis rate decreased(P<0.05)in the combined intervention group.(2)Protein expression:Compared with the sham operation group,the expression of tumor necrosis factor-α increased(P<0.05),while interleukin-10 and vascular endothelial growth factor expression decreased(P<0.05)in the model group.Compared with the model group,the expression of CXC chemokine receptor protein 4 increased(P<0.05)in the stem cell therapy group and combined intervention group,and the expression of tumor necrosis factor-α decreased(P<0.05)while interleukin-10 and vascular endothelial growth factor increased(P<0.05)in the stem cell therapy group,exercise preconditioning group,and combined intervention group.Compared with the stem cell therapy group,the expression of tumor necrosis factor-α decreased(P<0.05),while CXC chemokine receptor protein 4,interleukin-10,and vascular endothelial growth factor increased(P<0.05)in the combined intervention group.To conclude,exercise preconditioning can enhance the therapeutic effect of bone marrow mesenchymal stem cells in rats with acute myocardial infarction,which can inhibit cardiac remodeling,improve cardiac function,and delay the progress of heart failure.Its mechanism is related to the promotion of stem cell homing,inhibition of inflammatory response,and promotion of angiogenesis.
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Oral squamous cell carcinoma(OSCC),the most common type of head and neck tumor,is characterized by insidious onset,susceptibility to metastasis,short 5-year survival,and high mortality rate.Currently,various treatment modalities exist for OSCC;however,they inevitably give rise to issues related to non-specific cell death.Therefore,there is an urgent need to explore alternative therapeutic approaches for OSCC.This article provides a comprehensive overview of the recent advance-ments in OSCC treatment,aiming to offer new avenues for future therapeutic strategies.
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Objective:To design a fall detection system for elderly patients to solve the problem of elderly patients failing to detect accidental falls in time and to improve the efficiency of medical care.Methods:Based on real-time stream transmission protocol(RTSP),combined with YOLOv5 and Kalman algorithms,a fall detection system for elderly patients was designed by using Vue and Flask technologies.A visual background system management was established,and a unified management platform was provided for medical staff through comprehensive processing of multiple video streams to realize the autonomous detection and alarm of human fall behavior.30 healthy volunteers who underwent fall testing at Xijing Hospital of Air Force Medical University in 2020 to 2022 were selected and divided into normal walking group,squatting group and falling group according to the simulated behavioural categories,with 10 in each group.The fall detection performance was evaluated using two evaluation indicators:detection accuracy and detection speed to verify and determine whether the fall detection system for elderly patients can meet the requirements of timely and accurate fall detection and alarm.Results:The overall fall detection rate of the normal walking group,the squatting group and the falling group can reach 29 frames per second,and the accuracy rate can reach 95.24%.and the system can respond to the fall alarm in time.Conclusion:The fall detection system for elderly patients can assist medical staff to promptly detect and deal with the occurrence of falls,improve the efficiency of fall detection for elderly patients,and meet the real-time detection and alarm of fall behavior for elderly patients.
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Objective:To analyze the correlation between sagittal bearing movement and posterior tibial slope after Oxford unicompartmental knee arthroplasty (UKA) and its effect on clinical results.Methods:A total of 29 patients (30 knees) with anterior medial knee osteoarthritis who underwent Oxford third-generation UKA in the Department of Joint and Sports Medicine of the Second Hospital of Shanxi Medical University from January 2022 to March 2022 were retrospectively analyzed, including 7 males (8 knees) and 22 females (22 knees), aged 63.3±7.9 years (range, 47-84 years). The patients were divided into overhang group (9 knees) and non-overhang group (21 knees) according to whether there was overhang of the bearing in the sagittal X-ray film at 135° flexion after operation. The preoperative and postoperative Oxford Knee Score (OKS), tibial posterior slope angle and radiographic results of the bearing were compared between the two groups. Pearson correlation analysis was used to measure the relationship between postoperative sagittal bearing movement and OKS and tibial posterior slope.Results:All patients successfully completed the operation and were followed up for 7.2±1.1 months (range, 6-9 months). 30% (9/30) of the bearing were overhung. When the knee flexion was 135°, the position of the bearing in the overhang group was 83.33%±3.46%, and the posterior suspension distance was 1.12 ±1.80 mm, which was significantly higher than those in the non-overhang group (73.24%±3.40% and -4.45±2.37 mm, P<0.05). The bearing movement distance in the overhang group was 33.22%±8.51%, which was larger than that in the non-overhang group (23.36%±9.32%), and the difference was statistically significant ( P<0.05). The posterior tibial slope of the overhang group was 2.68°±2.20° at 6 months after operation, which was smaller than that of the non-overhang group (4.59°±2.69°), and the difference was statistically significant ( P<0.05). The OKS score was 19.00±8.84 in the overhang group and 19.14 ±7.00 in the non-overhang group at 6 months after operation, and the difference was not statistically significant ( P>0.05). Pearson correlation analysis showed that the overhang distance of the bearing was positively correlated with the bearing position at 135° knee flexion ( r=0.97, P<0.001), and negatively correlated with the posterior tibial slope ( r=-0.38, P=0.041). It was negatively correlated with the change of posterior tibial slope ( r=-0.37, P=0.045), positively correlated with the bearing movement distance ( r=0.68, P<0.001), and had no correlation with the position of the bearing at 0° knee flexion ( r=-0.15, P=0.423). The bearing movement distance was negatively correlated with the position of the bearing at 0° of knee flexion ( r=-0.82, P<0.001), positively correlated with the position of the bearing at 135° of knee flexion ( r=0.70, P<0.001), and negatively correlated with the posterior tibial slope ( r=-0.48, P=0.007). It was negatively correlated with the change of posterior tibial slope ( r=-0.39, P<0.001), and positively correlated with the overhang distance of bearing at 135° knee flexion ( r=0.68, P=0.033). Conclusion:The incidence of bearing overhang at Oxford UKA is 30%. The bearing overhang and the increase of the bearing movement distance are related to the decrease of the posterior tibial slope after the operation. Although no effect of bearing overhang on knee joint function was found, the posterior tibial slope should be adjusted during the operation to reduce the incidence of bearing overhang.
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Objective To investigate the relationship between cerebral atrophy and total burden of cerebral small vessel disease in patients with recent small subcortical infarct(RSSI).Methods A total of 194 elderly RSSI patients admitted to Department of Neurology of Changzhou Second People's Hospital Affiliated to Nanjing Medical University from September 2021 to November 2022 were recruited in this study.All patients completed cranial MRI examination and were divid-ed into a non-mild group 1(97 cases)and a moderate to severe group 1(97 cases)based on the to-tal burden of cerebral small vessel diseases(CSVD)imaging.Visual assessment scale was used to assess the severity of brain atrophy in the whole brain and various regions of the brain.According to the global cortical atrophy scale(GCA)score,all patients were divided into a non-mild group 2(88 cases)and a moderate to severe group 2(106 cases).Brain atrophy in various regions,medial temporal lobe atrophy(MTA)score,frontal temporal lobe atrophy(FTA)score,and posterior cortical atrophy(PA)score were evaluated.Their general clinical and imaging data were collected,multivariate logistic regression analysis was employed to analyze the relationship between GCA score and total burden of CSVD imaging in RSSI patients,and Spearman correlation analysis was further adopted to explore the correlation of GCA score and different parts of brain atrophy with total burden of CSVD imaging.Results When compared with the non-mild group 1,the moderate to severe group 1 had significantly larger proportions of having GCA score of 2-3 points,PA score of 2-3 points,MTA score of 2-4 points and FTA score of 2-4 points(P＜0.01).The ra-tio of having 2-4 points in total imaging burden score of CSVD was obviously higher in the mod-erate to severe group 2 than the non-mild group 2(P＜0.01).Multivariate logistic regression anal-ysis showed that age and total burden of CSVD imaging were independent risk factors for brain atrophy in RSSI patients(OR=1.184,95％CI:1.099-1.276,P=0.000;OR=3.537,95％CI:1.664-7.518,P=0.001).Spearman correlation analysis revealed that the total burden score of CSVD imaging was positively correlated with GCA,MTA,FTA and PA scores in RSSI patients(r=0.518,r=0.382,r=0.471,r=0.388,P=0.000).Conclusion The total burden of CSVD is an independent risk factor for GCA in elderly RSSI patients.The more serious the total burden of CSVD is,the higher the grade of GCA is.The total burden of CSVD is related to the whole brain and brain atrophy in other different regions of the brain.
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@#Non-small cell lung cancer (NSCLC) is one of the most common types of cancer in the world and is an important cause for cancer death. Although the application of immunotherapy in recent years has greatly improved the prognosis of NSCLC, there are still huge challenges in the treatment of NSCLC. The immune microenvironment plays an important role in the process of NSCLC development, infiltration and metastasis, and they can interact and influence each other, forming a vicious circle. Notably, single-cell RNA sequencing enables high-resolution analysis of individual cells and is of great value in revealing cell types, cell evolution trajectories, molecular mechanisms of cell differentiation, and intercellular regulation within the immune microenvironment. Single-cell RNA sequencing is expected to uncover more promising immunotherapies. This article reviews the important researches and latest achievements of single-cell RNA sequencing in the immune microenvironment of NSCLC, and aims to explore the significance of applying single-cell RNA sequencing to analyze the immune microenvironment of NSCLC.
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Objective To establish an allogeneic rat model of endometriosis and to evaluate the effects of gonadotropin-releasing hormone (GnRH) agonist GenSci006 on experimental rat endometriosis. Methods Endometrium from SPF grade donor female SD rats were transplanted onto the abdominal wall of recipient female rats to construct an allogeneic endometriosis model. The rats undergoing sham surgery were divided into the sham group. Three weeks later, the length, width and height of the ectopic endometrium were measured, and the volume of the endometrium (V1) was calculated before drug administration. The modeling rats were randomly divided into four groups: model group, triptorelin group (0.25 mg/kg), GenSci006-1 group (0.125 mg/kg) and GenSci006-2 group (0.25 mg/kg). Each group had 16 rats and received a single dose of the corresponding drug. The sham group and model group were administered an equal volume of solvent. Three weeks after administration, ectopic endometrium was measured to calculate the volume V2 and inhibition rate. The effect of GenSci006 on rat uterus and ovarian tissues was assessed by comparing organ coefficients and changes in pathological sections. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of serum estradiol (E2), progesterone (P4), follicle stimulating hormone (FSH), and luteinizing hormone (LH). Real-time fluorescent quantitative PCR was used to detect the expression of GnRH receptor (GnRHR) mRNA in the hypothalamus and pituitary. Western blot was used to detect the expression of estradiol receptor alpha (ERα), beta (ERβ) and progesterone receptor (PR) in ectopic endometrium. Results Three weeks after administration, compared with the model group, the body weight of rats in the triptorelin and GenSci006-2 groups significantly increased (P < 0.05), while the volume of ectopic endometrium significantly decreased (P < 0.05). Compared with the sham group, the model group showed no significant changes in uterine and ovarian organ coefficients or endometrial thickness (P > 0.05). Compared with the model group, the uterine organ coefficients and endometrial thickness were significantly reduced in the triptorelin and GenSci006-2 groups (P < 0.05). Compared with the sham group, the serum levels of E2, P4, FSH and LH in the model group showed no significant changes (P > 0.05). Compared with the model group, the ovarian organ coefficient and serum P4 levels of rats in the Triptorelin, GenSci006-1, and GenSci006-2 groups were significantly reduced (P < 0.05), while the serum LH levels of rats in the GenSci006-1 group were significantly increased (P < 0.05). However, there were no significant changes in serum E2 and FSH levels in each group (P > 0.05). Compared with the model group, the expression levels of GnRHR mRNA in the pituitary tissue of rats in the triptorelin and GenSci006-2 groups were significantly downregulated (P < 0.05), with no significantly changes in the hypothalamus (P > 0.05). There were no significant changes in the expression level of GnRHR mRNA in the hypothalamus or the protein levels of ERα, ERβ and PR in the ectopic endometrial tissue in any group (P > 0.05). Conclusion The allogeneic endometriosis rat model is a suitable animal model for screening and evaluating drugs for treating endometriosis. The volume of ectopic endometrium, inhibition rate, uterine and ovarian organ coefficients, and serum E2 levels may serve as indicators for detecting drug efficacy.
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Objective To explore the causal relationship among 731 types of immune cells and breast cancer. Methods Genome-wide association data for immune cells and breast cancer were used. Mendelian randomization analysis was performed using the inverse variance weighting (IVW) and weighted median (WM) methods, and sensitivity analysis was conducted to assess heterogeneity and pleiotropy. Results A total of 19 immune cell phenotypes were identified to potentially have a causal association with breast cancer, using IVW as the main analysis method (P>0.05) and correcting P values using the false discovery rate method at a significance level of 0.05, excluding reverse causality. Of these, eight and 11 immune phenotypes may increase and decrease the risk of breast cancer, respectively. Conclusion This study explored the causal relationship between immune cells and breast cancer. Results show that certain immune cell phenotypes could serve as predictive markers for the early diagnosis of breast cancer and the development of new immunotherapeutic strategies.
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Based on the pathogenesis of “tendon off-position and joint subluxation”， combined with modern ana-tomy and biomechanics， the characteristic manifestations of “tendon off-position” and “joint subluxation” of the knee and the intrinsic connection between them are clarified. Through sorting out the relationship between “tendon off-position and joint subluxation” and knee osteoarthritis （KOA） in modern research， it is believed that “tendon off-position and joint subluxation” is the key mechanism for the occurrence and development of KOA， and accordingly， it is proposed to take the diet as the guide， use bone manipulation for external diagnosis and treatment， use traditional Chinese medicine decoction for internal treatment， and use Daoyin exercise throughout the whole process as the strategy for KOA's comprehensive traditional Chinese medicine treatment to improve the clinical effectiveness.
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ObjectiveTo investigate the depression status and its influencing factors in HIV/AIDS patients receiving antiviral therapy. MethodsFrom July 2022 to September 2022， successive sampling method was used to recruit HIV/AIDS patients receiving antiviral therapy from antiviral treatment institutions in Nanjing， and they were instructed to fill out anonymous questionnaires. The questionnaire collected the basic information of patients， and depression， HIV stigma score and social support level were investigated by Patient Health Questionnaire-9 （PHQ-9）， Berger HIV stigma scale （BHSS） and Multidimensional Scale of Perceived Social Support （MSPSS）. Multivariate Logistic regression was used to analyze the influencing factors of depression. ResultsA total of 1879 valid questionnaires were collected in this study， and the detection rate of depression was 50.1%. The results of multivariate logistic analysis showed that compared with patients with middle school or below， the risk of depression was lower for those with postgraduate or above ［OR=0.534， 95%CI （0.341， 0.835）， P=0.006］. Compared with antiviral therapy duration<1 year， antiviral therapy duration for 1 to 5 years ［OR=0.729， 95%CI （0.536， 0.991）］， >5 to 10 years ［OR=0.516， 95%CI （0.379， 0.702）］， >10 years ［OR=0.603， 95%CI （0.375， 0.969）］ was associated with a lower risk of depression. High level of social support was a protective factor for depression in HIV/AIDS patients compared with middle and low level of social support ［OR=0.430， 95% CI（0.349， 0.530）， P < 0.001］. There was a higher risk of depression with side effects than without side effects ［OR=2.260， 95%CI （1.833， 2.786）， P < 0.001］. The higher the score on the HIV stigma scale， the higher the possibility of depression was. ConclusionThe detection rate of depression of patients receiving antiviral therapy in Nanjing is high. After starting antiviral therapy， we should strengthen the monitoring of side effects and psychological status of patients， carry out psychological intervention， alleviate psychological problems， and improve the quality of life of patients receiving antiviral therapy.
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@#Objective To compare the short-term clinical effects of Da Vinci robot-assisted thoracic surgery (RATS) and video-assisted thoracoscopic surgery (VATS) in the treatment of posterior mediastinal tumors, and to explore the advantages of RATS posterior mediastinal tumor resection. Methods The clinical data of patients who underwent posterior mediastinal tumors resection through the lateral chest approach admitted to the same medical group in the Department of Thoracic Surgery of the First Hospital of Lanzhou University between January 2019 to January 2023 were retrospectively analyzed. According to the different surgical methods, the patients were divided into a RATS group and a VATS group. The clinical data were compared between the two groups. Results A total of 85 patients were included in this study. There were 39 patients in the RATS group, including 25 females and 14 males, with an average age of 47.6±13.0 years, and 46 patients in the VATS group, including 14 males and 32 females, with an average age of 45.3±14.7 years. All patients completed the operation successfully. The hospitalization cost in the RATS group was significantly higher than that in the VATS group (P<0.001), and the white blood cell count and neutrophilic granulocyte percentage on the first day after operation in the RATS group were lower than those in the VATS group, and the differences were statistically significant (P<0.05). The operative time, intraoperative bleeding, postoperative hospital stay, white blood cell count and neutrophil percentage on the third postoperative day, visual analogue scale score on the first and third postoperative days, duration of analgesic pump use, postoperative 12 h oxygen saturation (no oxygen inhalation), postoperative down bed time, total thoracic drainage volume, duration of drainage tube retention, and postoperative complication rates were not statistically different between the two groups (P>0.05). There was no perioperative death, conversion to thoracotomy or serious perioperative complications in both groups. Conclusion RATS resection of posterior mediastinal tumor via lateral thoracic approach is safe and feasible, and its short-term effect is similar to that of VATS via lateral thoracic single-hole approach. It is worth further comparative study to explore its benefit and cost performance.
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Background/Aims@#The shortage of donor liver hinders the development of liver transplantation. This study aimed to clarify the poor outcomes of functionally marginal liver grafts (FMLs) and provide evidence for the improvement of ischemia-free liver transplantation (IFLT) after FML transplantation. @*Methods@#Propensity score matching was used to control for confounding factors. The outcomes of the control group and FML group were compared to demonstrate the negative impact of FMLs on liver transplantation patients. We compared the clinical improvements of the different surgical types. To elucidate the underlying mechanism, we conducted bioinformatic analysis based on transcriptome and single-cell profiles. @*Results@#FMLs had a significantly greater hazard ratio (HR: 1.969, P=0.018) than did other marginal livers. A worse 90-day survival (Mortality: 12.3% vs. 5.0%, P=0.007) was observed in patients who underwent FML transplantation. Patients who received FMLs had a significant improvement in overall survival after IFLT (Mortality: 10.4% vs 31.3%, P=0.006). Pyroptosis and inflammation were inhibited in patients who underwent IFLT. The infiltration of natural killer cells was lower in liver grafts from these patients. Bulk transcriptome profiles revealed a positive relationship between IL-32 and Caspase 1 (R=0.73, P=0.01) and between IL-32 and Gasdermin D (R=0.84, P=0.0012). @*Conclusions@#FML is a more important negative prognostic parameter than other marginal liver parameters. IFLT might ameliorate liver injury in FMLs by inhibiting the infiltration of NK cells, consequently leading to the abortion of IL-32, which drives pyroptosis in monocytes and macrophages.
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Objective To investigate the mechanism of fractionated low-dose ionizing radiation (LDIR) in the induction of EA.hy926 cell senescence. Methods EA.hy926 cells were irradiated with X-ray at 0, 50, 100, and 200 mGy × 4, respectively, and cultured for 24, 48, and 72 h. Several indicators were measured, including the levels of cellular senescence-associated β-galactosidase (SA-β-gal) staining, mRNA levels of senescence-associated cell cycle protein-dependent kinase inhibitor genes CDKN1A and CDKN2A, reactive oxygen species (ROS), total antioxidant capacity (T-AOC), and phosphorylated H2A histone family member X (γ-H2AX). Results After 4 fractionated LDIR, compared with the control group, the treatment groups showed increased nucleus area, blurred cell edge, and increased SA-β-gal positive area (P < 0.05) at 24, 48 and 72 h. After 4 fractionated LDIR, the mRNA level of CDKN1A increased in the 100 and 200 mGy × 4 groups at 24 and 48 h (P < 0.05), and CDKN2A mRNA level increased in the 100 and 200 mGy × 4 groups at 48 and 72 h (P < 0.05). The fluorescence intensity of ROS increased in treatment groups at 24, 48, and 72 h after 4 fractionated LDIR (P < 0.05). After 4 fractionated LDIR, the T-AOC level increased in the 100 and 200 mGy × 4 groups at 24 h (P < 0.05), and T-AOC level increased in all treatment groups at 48 and 72 h (P < 0.05). After 4 fractionated LDIR, γ-H2AX fluorescence intensity increased in all treatment groups at 24 h (P < 0.05), and the fluorescence intensity increased in the 100 and 200 mGy × 4 groups at 48 and 72 h (P < 0.05). Conclusion Fractionated LDIR can induce cellular senescence in EA.hy926 cells by impacting the cellular oxidation-antioxidation and oxidative damage levels, and the effects were relatively evident at 100 and 200 mGy.
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OBJECTIVE To investigate the intervention effect and potential mechanism of breviscapine on hepatic fibrosis （HF） in rats based on the transforming growth factor-β（1 TGF-β1）/Smad2/extracellular signal-regulated protein kinase 1（ERK1） and Kelch-like epichlorohydrin-associated protein 1（Keap1）/nuclear factor-erythroid 2-related factor 2（Nrf2）/heme oxygenase-1（HO-1） pathways. METHODS Totally 60 rats were randomly divided into normal control group， model group， breviscapine low-dose， medium-dose and high-dose groups （5.4， 10.8， 21.6 mg/kg）， and colchicine group （positive control， 0.45 mg/kg）， with 10 rats in each group， half male and half female. Except for the normal control group， HF model of the other groups was induced by carbon tetrachloride. Subsequently， each drug group was given corresponding medicine by gavage once a day for 28 days. The liver appearance of rats in each group was observed and their liver coefficients were calculated. The levels of alanineaminotransferase （ALT） and aspartate aminotransferase （AST）in serum， those of ALT， AST， superoxide dismutase （SOD），malondialdehyde （MDA） and glutathione peroxidase （GSH- Px） in liver tissue were detected. The liver tissue inflammatory and fibrotic changes were observed. The protein and mRNA expressions of TGF-β1， Smad2， ERK1， Nrf2， Keap1 and HO-in liver tissue were detected. RESULTS Compared with the normal control group， the model group showed large areas of white nodular lesions in the liver， obvious inflammatory cell infiltration and collagen fiber deposition. The body weight， the levels of SOD and GSH-Px in liver tissue， the protein and mRNA expressions of Nrf2 and HO-1 were significantly lowered in the model group （P＜0.05）； the liver coefficient， the percentage of Masson staining positive area， ALT and AST levels of serum and liver tissue， MDA level of liver tissue， the protein and mRNA expressions of TGF-β1， Smad2， ERK1 and Keap1 were significantly increased （P＜0.05）. Compared with the model group， the liver lesions of rats in each drug group were improved， and the above quantitative indexes were generally reversed （P＜0.05）. CONCLUSIONS Breviscapine has a good intervention effect on HF rats， which may be related to inhibiting TGF-β1/Smad2/ERK1 pathway for anti-fibrosis and regulating Keap1/Nrf2/HO-1 pathway to inhibit oxidative stress.