Background Coal workers' pneumoconiosis is a serious occupational disease in China. Exhaled volatile organic compounds (VOCs) can serve as the "breath fingerprint" of internal pathological processes, which provides a theoretical basis for exhaled VOCs to be used as potential non-invasive biomarkers for early diagnosis of coal workers' pneumoconiosis. Objective To screen out the characteristic VOCs and important characteristic VOCs of exhaled air in patients with coal workers' pneumoconiosis, and to explore the potential of these VOCs as biomarkers for early non-invasive diagnosis of the disease. Methods In this study, 27 VOCs in the exhaled breath of 22 patients with stage I coal workers' pneumoconiosis, 77 workers exposed to dust, and 92 healthy controls were quantitatively detected by thermal desorption gas chromatography-mass spectrometry (TD-GC-MS). Substances with P<0.05 in univariate analysis and variable importance projection (VIP) >1 in supervised orthogonal partial least squares discriminant analysis (OPLS-DA) model were selected as the characteristic VOCs for early diagnosis of coal workers' pneumoconiosis. Age was included in the LASSO regression model as a covariate to screen out important characteristic VOCs, and the diagnostic performance was evaluated by receiver operating characteristic (ROC) curve. Spearman correlation was further used to explore the correlation between important characteristic VOCs and clinical lung function indicators. Results Through univariate analysis and OPLS-DA modeling, 8 VOCs were selected, including 2-methylpentane, 3-methylpentane, n-hexane, methylcyclopentane, n-heptane, methylcyclohexane, 4-methyl-2-pentanone, and 2-hexanone, in exhaled breath of patients with coal workers' pneumoconiosis. The concentrations of 4 VOCs, including 3-methylpentane, n-hexane, 4-methyl-2-pentanone, and 2-hexanone, showed a decreasing trend with the increase of dust exposure years. By LASSO regression, the important characteristic VOCs of the coal workers' pneumoconiosis group and the dust exposure group were n-hexane, methylcyclohexane and 4-methyl-2-pentanone, and the important characteristic VOCs of the coal workers' pneumoconiosis group and the healthy group were 2-methyl-pentane and 4-methyl-2-pentanone. The ROC analysis showed that the area under the curve (AUC) of n-hexane, methylcyclohexane, and 4-methyl-2-pentanone were 0.969, 0.909, and 0.956, respectively, and the AUC of combined diagnosis was 0.988 and its Youden index was 0.961, suggesting that these results can serve as a valuable reference for further research on early diagnosis. The Correlation analysis found that there was a positive correlation between n-hexane and lung function indicators in the important characteristic VOCs, indicating that it could indirectly reflect the obstruction of lung function ventilation, further proving that important characteristic VOCs have the potential to monitor lung function decline. Conclusion Three important characteristic VOCs selected in this study have the potential to be used as non-invasive biomarkers for early diagnosis and disease monitoring of coal workers' pneumoconiosis, and are worthy of further study and verification.

Objective To investigate the mid- to long-term follow-up results of ascending aorta (AAO)-descending thoracic aorta (DTA) bypass grafting via median sternotomy incision for the treatment of complex aortic arch coarctation. Methods A retrospective analysis was conducted on the clinical data of patients with complex aortic arch coarctation who underwent AAO-DTA bypass grafting via median sternotomy incision at the First Hospital of Tsinghua University from August 2004 to May 2017. Results A total of 7 patients were enrolled, including 4 males and 3 females, aged (13.3±4.6) years, and weighted (40.2±12.2) kg. Six (85.7%) patients had concomitant upper limb hypertension. Four patients were aortic arch coarctation combined with intracardiac malformations, two were post-operative restenosis, and 1 was post-operative restenosis combined with intracardiac malformation. All patients underwent surgery under cardiopulmonary bypass. There were no perioperative deaths or major complications. The pre-operative upper-lower limb pressure difference was (39.3±19.2) mm Hg, which decreased to (2.9±2.7) mm Hg post-operatively (P<0.01). The follow-up period was (14.9±5.9) years. There were no long-term deaths or artificial graft-related complications. Except for one patient who still had mild hypertension, the blood pressure of the remaining patients returned to normal. Conclusion AAO-DTA bypass grafting via median sternotomy incision for the treatment of complex aortic arch coarctation can effectively reduce upper limb blood pressure and the upper-lower limb arterial pressure difference, has fewer complications, and demonstrates satisfactory mid- to long-term efficacy.

NDFIP1 has been previously reported as a tumor suppressor in multiple solid tumors, but the function of NDFIP1 in NSCLC and the underlying mechanism are still unknown. Besides, the WW domain containing proteins can be recognized by NDFIP1, resulted in the loading of the target proteins into exosomes. However, whether WW domain-containing transcription regulator 1 (WWTR1, also known as TAZ) can be packaged into exosomes by NDFIP1 and if so, whether the release of this oncogenic protein via exosomes has an effect on tumor development has not been investigated to any extent. Here, we first found that NDFIP1 was low expressed in NSCLC samples and cell lines, which is associated with shorter OS. Then, we confirmed the interaction between TAZ and NDFIP1, and the existence of TAZ in exosomes, which requires NDFIP1. Critically, knockout of NDFIP1 led to TAZ accumulation with no change in its mRNA level and degradation rate. And the cellular TAZ level could be altered by exosome secretion. Furthermore, NDFIP1 inhibited proliferation in vitro and in vivo, and silencing TAZ eliminated the increase of proliferation caused by NDFIP1 knockout. Moreover, TAZ was negatively correlated with NDFIP1 in subcutaneous xenograft model and clinical samples, and the serum exosomal TAZ level was lower in NSCLC patients. In summary, our data uncover a new tumor suppressor, NDFIP1 in NSCLC, and a new exosome-related regulatory mechanism of TAZ.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Carrier Proteins/metabolism* ; Cell Line ; Cell Proliferation ; Exosomes/metabolism* ; Lung Neoplasms/genetics* ; Membrane Proteins/metabolism* ; Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism*

Objective:To investigate the value of three-dimensional (3D) CT in diagnosing cricoarytenoid dislocation.Methods:From January 2021 to December 2021, 31 patients with unilateral cricoarytenoid dislocation who had been treated by reduction forceps at the Affiliated BenQ Hospital of Nanjing Medical University were collected retrospectively, and their voice recovered or improved significantly after therapy. The preoperative CT images were reconstructed by volume rendering (VR). The dislocated side (left and right), type of dislocation (total dislocation and subluxation), and dislocation direction (anterior, posterior, internal and external dislocation) of cricoarytenoid dislocation were observed. According to arytenoid articular surface of cricoid cartilage exposed completely or not (caused by arytenoid displacement), they were divided into complete dislocation and subluxation. According to the direction of arytenoid displacement and the part of arytenoid articular surface of cricoid cartilage exposed, they were divided into anterior, posterior, internal and external dislocation. According to the shape of the vocal cords on laryngoscope, anterior and posterior dislocation of each case was judged, and then compared with that of CT.Results:On VR images, there were 28 cases of cricoarytenoid subluxation (90.3%, 28/31) and 3 cases of complete dislocation (9.7%, 3/31). Left cricoarytenoid dislocation was 26 cases (83.9%, 26/31) and right cricoarytenoid dislocation was 5 cases (16.1%, 5/31). Posterior dislocation was 28 cases (90.3%, 28/31) and anterior dislocation was 3 cases (9.7%, 3/31). There were 23 cases of internal dislocation (74.2%, 23/31), 2 cases of external dislocation (6.4%, 2/31), and 6 cases without obvious internal and external dislocation (19.4%, 6/31). Three cases of complete dislocation were left posterior internal dislocation.There were 24 cases of left posterior dislocation (77.4%, 24/31), 4 cases of right posterior dislocation (12.9%, 4/31), 2 cases of left anterior dislocation (6.4%, 2/31) and 1 case of right anterior dislocation (3.2%, 1/31). On laryngoscope, there were 19 cases of posterior dislocation (61.3%, 19/31), 9 cases of anterior dislocation (29.0%, 9/31), 3 cases were difficult to assess (9.7%, 3/31) because of aryepiglottic fold covering. Sixteen cases (55.2%, 16/28) were consistent with 3D CT, and 12 cases (42.8%, 12/28) were inconsistent.Conclusion:The 3D CT is a reliable method to evaluate cricoarytenoid dislocation, which can show dislocated side, type and direction of cricoarytenoid dislocation clearly.

Objective:To evaluate the clinical outcomes of patients with single spinal metastasis of thoracic, lumbar or sacral vertebra treated with microwave ablation in situ.Methods:For 28 patients with single spinal metastasis of thoracic, lumbar or sacral vertebra, detailed and personal surgical plans were carried out. Instead of en bloc resection, hyperthermia ablation in situ was performed followed by strengthening procedures under the guidance of G-arm fluoroscopy machine. Intraoperatively, spinal cord and nerve root were properly protected. The bone defects were reconstructed by bone cement after the diseased lesions were revomed. All patients were followed up for almost 1 year postoperatively. During follow-up, X-ray and MRI images were obtained, and the level of pain and neurologic outcomes were also examined.Results:All 28 patients successfully received microwave ablation in situ. The average ablation time was approximately 8 minutes and the average amount of bone cement implanted was approximately 10.5 ml. The pain scores of digital pain classification before and 3 months after operation were 7.86±1.58 and 3.07±1.89( P<0.05). The postoperative neurological function of 22 patients was improved than that before operation. No significant changes were observed in 5 patients. The neurological function of the affected limb was relieved, whereas the symptoms of the healthy limb were slightly worse in the remaining case. Conclusions:Microwave ablation in situ is a feasible and effective surgical method for single spinal metastasis of thoracic, lumbar or sacral vertebra. It might possess many advantages, such as clear surgical field, smaller incisions, less bleeding, and safe margins during the operations. Further more, it could significantly relieve pain, restrict tumor growth, and improve the quality of life of patients. It is an innovative and distinctive therapeutic alternative for single spinal metastasis, which deserves widespread application.

Objective: To compare the carcinogenic abilities of CD133⁺CD44⁺ laryngeal cancer stem cells and general laryngeal cancer stem cells and to identify the mechanism underlying the action of miRNAs. Methods: Solid tumor-derived laryngeal carcinoma stem cells and Hep-2-derived laryngeal carcinoma stem cells were cultured, and CD133⁺CD44⁺ laryngeal cancer stem cells were sorted by flow cytometry. Boden chamber invasion assay, cell migration assay and tumor formation assay were then performed to compare the invasion, migration and tumorigenic abilities of CD133⁺CD44⁺ laryngeal cancer stem cells and general laryngeal cancer stem cells. And then, miRNAs isolated from two laryngeal cancer stem cells were detected and analysed with miRNA chip. Results: (1)In Boyden chamber invasion assay, the cell invasion rate of CD133⁺CD44⁺ laryngeal cancer stem cells was obviously higher (80.2%±2.3% vs. 63.9%±3.2%, t=5.011, P=0.027); (2)CD133⁺CD44⁺ laryngeal cancer stem cells also had higher mobility in cell migration assay (82.9%±1.1% vs. 70.9%±0.6%, t=4.514, P=0.031); (3)In tumor formation assay, the tumor formation rate of CD133⁺CD44⁺ laryngeal cancer stem cells was also higher (80% vs. 50%). What′s more, we identified 15 miRNAs that were significantly upregulated in CD133⁺CD44⁺ laryngeal cancer stem cells and 3 miRNAs that were significantly downregulated in CD133⁺CD44⁺ laryngeal cancer stem cells, compared with normal laryngeal cancer stem cells. Conclusions CD133⁺CD44⁺ laryngeal cancer stem cells have stronger invasion, migration and tumorigenic abilities compared with normal laryngeal cancer stem cells, and the difference of miRNAs′ expression is one of the possible causes.

Objective To explore the curative effect of knee flexion deformity on spastic cerebral palsy treatment method.Methods All of 30 patients with spastic cerebral and knee flexion deformity were randomly divided into two groups:traditional operation group and modified operation group,using the commonly used operation (In 15 cases,with traditional hamstring post surgery) and) modified operation (In 15 cases,with modified hamstring post surgery),two groups of patients were treated with Ilizarov external fixation drafting device in the correction of knee flexion deformity after soft tissue release.Adjustment began 7 days after the soft tissue release operation of external fixation,and stretched approximately 0.2 degrees each time,3 times/d,until knee flexion deformity was corrected to hyperextension for 10 degree and maintained for 3 weeks,and the flexion contracture degree of knee joint was measured every 2 weeks;then the Ilizarov external fixation drafting device was removed.Then wear a walking straight leg brace for more than 3 months,until the knee walking function is good.Clinical evaluation included the joint pain index,walking function index,knee flexion deformity degree and range of joint motion score of Dimeglio standard.Results Flexion contracture deformity of knee joint in 30 cases (60 knees) was corrected when Ilizarov external fixator was removed,knee extension to 0 degrees-5 degrees.The two groups of patients had the knee flexion angle range of-1.2 degrees to 13.3 degrees,with an average of (7.32°±3.41°) after removed of the walking straight leg brace,in which 4 cases (8 joints) got recurrent deformity of 10°-15° at the time of removing of the walking straight leg brace.Knee activity significantly was improved at the end of treatment.60 cases of knee joint activity were close to normal,with flexion of 100 degrees to 135 degrees,extension of 0 degrees to 10 degrees.Two groups of patients were statistically significantly improved before and after surgery.Curative effect comparison:The walking function index of the modified operation group was obviously superior to that of the traditional operation group,there was significant statistical difference.There were no statistically significant differences in pain index,knee flexion,and range of joint motion.Conclusion For the treatment of flexion deformity of the knee joint in spastic cerebral palsy,traditional surgery using the semitendinosus and gracilis,post and semimembranosus lysis,combined with the Ilizarov draft external fixation could improve the walking function of the patients,simplify the surgical incision and reduce trauma.As a result,modified hamstring post surgery is an ideal,effective treatment method.

Objective As a classical approach for hyperthermic ablation,microwave ablation (MWA) has been widely used in the treatment of tumors that cannot be removed by traditional surgery.MWA devitalizes the neighboring tissue and kills tumor cells by thermal diffusion.In the last two decades,this technique has been improved for treating malignant bone tumor in our institute.In situ ablation has already replaced en bloc resection and achieved satisfactory treatment outcomes.This study explores whether tumor cell death induced by MWA would cause the release of immunogenic tumor antigens and tumor-specific immune responses.Methods Three models of MWA were established using osteosarcoma cell lines from the mouse,rat,and human,respectively.The expression of immunogenic molecules was measured during in vitro and in situ ablation with different ablation time and group design.Results The injection of tumor vaccines made from tumor cells or supernatant treated with in vitro ablation resulted in substantial inhibition of tumor cell growth in tumor-bearing animal models.The CDs + T cells induced by vaccines played a key role in the process.The effector cells released cytokines,IFN-γand TNF-α,to inhibit tumor cell growth and also trigger Fas/FasL-mediated apoptosis.Conclusions MWA-treated osteosarcoma cells can be used to induce specific antitumor immunogenic effects.Therefore,in situ MWA combined with immunotherapy provides an alternative treatment method for patients who have trouble due to their insensitivity to chemotherapy.

Objective To investigate the evolution of cognitive function and its influence factors,so as to provide evidence for guiding treatment of cognitive impairment after stroke.Methods A total of 98 cases of patients with stroke admitted in the First and Second Affiliated Hospital of Medical College of Xi'an Jiaotong University and Shaanxi Provincial People's Hospital between April and September 2009 were enrolled and recruited.Mini-mental state examination(MMSE) and Montreal cognitive function rating scale (MoCA) were adopted to assess the evolution of cognition at acute phase( within 2 weeks),6 weeks,and 12 weeks after stroke among patients within 2 weeks after onset,questionnaire score≤56,without aphasia and consiousness disturbance and at least one side of upper extremities muscle force ≥ grade 3.Results When using MMSE scale as criteria,the incidence of cognitive impairment was 24.5% at acute phase,12.1% at 6 weeks and 9.9% at 12 weeks after stroke,while the incidence was 86.8%,68.2%,and 38.0% respectively when using MoCA scale as criteria.The scales of MMSE and MoCA were increased and the incidence of cognitive impairment was decreased within 12 weeks after stroke.Logistic regression analysis indicated that,advanced age( β = -0.124 ),hypertension ( β = -3.705 ),low education level ( β = 0.560 )and depression after stroke ( β =4.613 ) were related with cognitive impairment after stroke ( all P values ＜0.05 ); low education level ( β = 0.710 ),coronary heart disease ( β = -3.649 ),elevated total cholesterol (TC) ( β = -3.361 ) and low density lipid cholesterol (LDL-C) ( β = - 5.833 ),and depression ( β =-3.612) delayed recovery of cognition after stroke.Conclusions The cognitive function improves and the incidence of cognitive impairment lowers as the time goes on within 12 weeks after stroke.The factors that may affect the improvement of cognitive function include low educational level,coronary heart disease,elevated TC and LDL-C,and post-stroke depression.

ObjectiveTo develop an antibody-array system for multiple detection of antibodies against Japanese B encephalitis virus (JEV),Tick-borne encephalitis virus (TBV),Dengue virus ( DENV ),West Nile virus (WNV),Western equine encephalitis virus (WEEV) and East Equine encephalitis virus (EEEV).MethodsRecombined antigens were spotted on array as capture antigens.Specific antibodies were detected by using a sandwich ELISA format.Rabbit antiserum was employed to select and confirm the specificity of antigens and to optimize the conditions of the assay.The detection efficiency of the system was validated by 40 clinical suspected serum samples and compared with the relative ELISA assays.ResultsEleven recombined antigens were selected as diagnostic antigens with high specificity.Better detection could be achieved when scale of antigen concentrations were within 0.125-0.900 mg/ml and the serum dilutions were 1:100-1:1000.When detecting the 26 clinical suspected TBE serum samples,20 were IgG positive (76.9％),and 17 were IgM positive (65.3％) which was 96.1％ and 84.6％ consistent with the relevant ELLSA tests,the 8 clinical suspected JEV serum samples,4 were IgG positive (50.0％),and 5 were IgM positive (62.0％),which was 86.3％ and 90.1％ consistent with the relevant ELLSA tests.As for the 22 DEN serum samples,13 were IgG positive (60％) and 15 were IgM positive (68％) which was 85％ and 93％ consistent with ELISA.The specificity of the assay was 100％ and the sensitivity was higher than the relative ELISAs.ConclusionThe developed antibody-array is highly specific and reliable,which could be used for the detection of antibodies against the 6 arboviruses.