Preoperative prediction of vasculogenic mimicry in lung adenocarcinoma using a CT radiomics model.

AIM: To develop and validate a non-invasive computed tomography (CT)-based radiomics model for predicting vasculogenic mimicry (VM) status in lung adenocarcinoma (LA). MATERIALS AND METHODS: Two hundred and three patients with LA were enrolled retrospectively and grouped into training and test groups with a ratio of 7:3. Uni- and multivariate logistic regression analyses were performed in the training cohort to screen the independent clinical and radiological factors for VM, and the clinical model was then established. A radiomics model was established based on the rad-scores through support vector machine (SVM). A radiomics nomogram model was subsequently constructed by combining the rad-score with clinical-radiological factors. The receiver operating characteristic curve (ROC), calibration curves, and decision curve analysis (DCA) were conducted to evaluate the performance of the three models. RESULTS: Nine selected radiomics features were selected for the radiomics model and the maximum length and spiculation sign were constructed for the clinical model. The radiomics nomogram model integrating the maximum length, spiculation sign, and rad-score yielded the best AUC in both the training (AUC = 0.925) and test cohorts (AUC = 0.978), in comparison with the radiomics model (AUC = 0.907 and 0.964, in both the training and test cohorts) and the clinical model (AUC = 0.834 and 0.836 in both training and test cohorts). CONCLUSIONS: The CT-based radiomics nomogram model showed satisfying discriminating performance for preoperatively and non-invasively predicting VM expression status in LA patients.

[En1 promotes cell proliferation and migration via Hedgehog signaling pathway in esophageal squamous cell carcinoma].

Objective: To explore the function and mechanism of transcription factor En1 in esophageal squamous cell carcinoma (ESCC). Methods: The correlations of En1 with prognosis were analyzed using the overall survival data of 9 397 pan-cancer patients and progression-free survival data of 4 349 pan-cancer patients from The Cancer Genome Atlas (TCGA) database. The En1 expression data in 53 and 155 cases of ESCC and their paired adjacent tissues were from Gene Expression Omnibus (GEO) database and National Genomics Data Center-Genome Sequence Archive(NGDC-GSA)database. Lentivirus was used to generate En1 stable knockout cell lines KYSE180 and KYSE450. The proliferation ability of the cells was detected by cell counting kit 8 and clone formation assay. The migration ability of the cells was detected by Transwell assay. The effect of En1 on the proliferation of ESCC was detected by xenograft experiment in BALB/c-nu/nu mice. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expressions of En1, glioma-associated oncogene family zinc finger 1 (GLI1), glioma-associated oncogene family zinc finger 2 (GLI2) and smoothened (SMO). Results: Pan-cancer data from TCGA showed that patients with low En1 expression had longer overall survival and progression-free survival than patients with high En1 expression (P< 0.001). Data from GEO and GSA databases also showed a high expression level of En1 in ESCC tissues compared with paired tissues (P＜0.001). Proliferation was inhibited after knockout of En1 in KYSE180 and KYSE450 cells (P＜0.001). The colony formation numbers decreased. The colony formation numbers of KYSE180 cells in the shEn1#1 group and the shEn1#2 group were 138.33±23.07 and 127.00±19.70, respectively, significantly lower than that of the shNC group 340.67±12.06 (P<0.001). The colony formation numbers of KYSE450 cells in the shEn1#1 group and the shEn1#2 group were 65.33±2.52 and 9.00±3.00, respectively, significantly lower than that of the shNC group 139.00±13.00 (P<0.001). The migration numbers was inhibited after knockout of En1 [the Transwell numbers of KYSE180 cells in the shEn1#1 group and the shEn1#2 group were 66.67±12.66 and 71.33±11.02, respectively, significantly lower than that of the shNC group 334.67±16.56 (P<0.001). The Transwell numbers of KYSE450 cells in the shEn1#1 group and the shEn1#2 group were 112.33±14.57 and 54.33±5.51, respectively, significantly lower than that of the shNC group 253.33±21.03 (P<0.001)]. Xenograft model showed a slower growth rate of shEn1#1 and shEn1#2 cell lines (P＜0.001). The tumor weights of KYSE450 cells in the shEn1#1 group and the shEn1#2 group were (0.046±0.026)g and (0.047±0.025)g, respectively, significantly lower than that of the shNC group (0.130±0.038)g (P＜0.001). After knockdown of En1, the relative expression levels of GLI1 in KYSE180 cells of the shEn1#1 group and the shEn1#2 group were 0.326±0.162 and 0.322±0.133, and the relative expression levels of GLI1 in KYSE450 cells of the shEn1#1 and shEn1#2 groups were 0.131±0.006 and 0.352±0.050, respectively, which were all lower than that in the shNC group (P＜0.01). After knockdown of En1, overexpression of GLI1 attenuated the inhibitory effect of knockdown of En1 on cell proliferation (P＜0.001), colony formation[the colony formation numbers of the shEn1#1-GLI1 group were 151.00±9.54, higher than 102.33±10.02 (P=0.004) of the shEn1#1-vector group] and migration [the migration numbers of the shEn1#1-GLI1 group were 193.67±10.07, higher than 109.33±11.50 (P<0.001) in the shEn1#1-vector group]. In clinical samples of ESCC, major regulatory factors of the Hedgehog pathway were up-regulated and the pathway was activated. Conclusion: En1 promotes the proliferation and migration of ESCC cells by regulating the Hedgehog pathway and can be used as a new potential target for targeted therapy of ESCC.

[Serum glycocalyx markers in patients after cardiac arrest: association with outcomes].

Objective: To assess the levels of serum glycocalyx markers in the first 24 hours after cardiac arrest (CA) and investigate their relationship with 30-day outcomes. Methods: A retrospective cohort study was conducted on prospectively collected data from CA patients, who were admitted to the intensive care units of the Affiliated Hospital of Xuzhou Medical University and obtained return of spontaneous circulation for more than 24 hours between September 2021 and October 2022. Serum samples obtained at the 24-hour after CA were utilized to measure the levels of glycocalyx markers, including heparan sulfate (HS), hyaluronic acid (HA), and syndecan-1 (Sdc-1). Patients were allocated into good function (CPC1-2) and poor function (CPC3-5) groups on the basis of cerebral performance category (CPC) at 30 days post-CA. Logistic regression analysis was used to determine the association between serum glycocalyx markers and neurological outcomes. Patients were regrouped in light of 30-d mortality and Cox regression analysis was used to determine the association between serum glycocalyx markers and 30-d mortality. Results: A total of 71 patients were included in the study, including 31 (43.7%) females and 40 (56.3%) males, with an average age of (59.0±17.0) years. The poor function group (n=49) demonstrated significantly elevated levels of HS and HA when compared to the good function group (n=22) [HS: 2 461.0(1 623.0, 5 492.0) µg/L vs 1 492.0 (914.0, 2 550.0) µg/L, P=0.008; HA: 124.0(97.0, 365.0)µg/L vs 337.0(135.0, 1 421.0) µg/L, P=0.033]. Adjusted logistic regression analysis revealed that HS was independently associated with poor neurological outcome [odds ratio (OR)=0.389, 95% confidence interval (CI): 0.182-0.828, P=0.014]. In the 30-day mortality analysis, the death group (n=32) exhibited significantly higher levels of HS and HA when compared to the survival group (n=39) [HS: 1 880.0(1 011.0, 3 554.0) µg/L vs 2 500.0(1 726.0, 6 276.0) µg/L, P=0.027; HA: 162.0(99.0, 537.0) µg/L vs 813.0(148.0, 1 531.0) µg/L, P=0.025]. Adjusted Cox regression analysis indicated that elevated levels of HS and HA were independent risk factors (HS: HR=1.697, 95%CI: 1.126-2.557, P=0.011; HA: HR=1.336, 95%CI: 1.047-1.705, P=0.020) for 30-day mortality. Conclusions: High level of serum HS in 24 hours after CA may serve as a potential predictive marker for both neurological function and 30-day mortality. However, high level of serum HA appears to primarily predict 30-day mortality. Sdc-1 does not seem to contribute to outcome prediction.

[Systemic disseminated nocardiosis in a patient with normal immune function: a case report].

Nocardiosis, characterized by poor prognosis and high mortality, is a local or systemic suppurative or granulomatous disease caused by Nocardia that is common in immunosuppressed individuals but rare in populations with normal immune function. This paper described one case of Nocardia gipuzkoensis disseminated infection in a patient with normal immune function by outlining the process of treatment, conducting literature review and by outlining the clinical characteristics, diagnostic criteria and standardized treatments of nocardia disease, in the hope of providing reference for subsequent treatment of rare Nocardia subspecies infections.

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial.

BACKGROUND: Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596). RESULTS: A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28], with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802). CONCLUSIONS: NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.

Effects of Breathing Patterns on Amide Proton Transfer MRI in the Kidney: A Preliminary Comparative Study in Healthy Volunteers and Patients With Tumors.

BACKGROUND: The amide proton transfer-weighted (APTw) imaging for kidney diseases is important. However, the breathing patterns on APTw imaging remains unexplored. PURPOSE: This study aimed to investigate the effects of intermittent breath-hold (IBH) and free breathing (FB) on renal 3D-APTw imaging. STUDY TYPE: Healthy volunteers were enrolled prospectively, and renal clear cell carcinoma (RCCC) patients were included retrospectively. POPULATION: 58 healthy volunteers and 10 RCCC patients. FIELD STRENGTH/SEQUENCE: 3-T, turbo spin echo, and fast field echo. ASSESSMENT: 3D-APTw imaging was scanned using the IBH and FB methods in volunteers and using the IBH method in RCCC patients. The image quality was evaluated by three observers according to the 5-point Likert scale. Optimal images rated at three points or higher were used to measure the APT values. STATISTICAL ANALYSIS: The measurement repeatability was assessed using the intraclass correlation coefficient (ICC) and the Bland-Altman plot. The APT values were analyzed using McNemar's test, one-way analysis of variance, and t test. RESULTS: 50 healthy volunteers and 8 RCCC patients were enrolled. Renal 3D-APTw imaging using the IBH method revealed a higher success rate (88% vs 78%). The ICCs were excellent in the IBH group (ICCs > 0.74) and were good in the FB group (ICCs < 0.74). No significant differences in the APT values among various zones using the IBH (P = 0.263) or FB method (P = 0.506). The mean APT value using the IBH method (2.091% ± 0.388%) was slightly lower than the FB method (2.176% ± 0.292%), but no significant difference (P = 0.233). The APT value of RCCC (4.832% ± 1.361%) was considerably higher than normal renal using the IBH method. CONCLUSIONS: The study demonstrated that the IBH method substantially increased the image quality of renal 3D-APTw imaging. Furthermore, APT values may vary between normal and tumor tissues. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Impaired function of skeletal stem cells derived from growth plates in ovariectomized mice.

INTRODUCTION: Mouse skeletal stem cells (mSSCs, CD45-Ter119-Tie2-CD51+Thy-6C3-CD105-CD200+population) are identified in growth plates (GP) and play important roles in bone regeneration. However, the role of mSSCs in osteoporosis remains unclear. MATERIALS AND METHODS: The GP were stained by HE staining, and the mSSC lineage was analyzed by flow cytometry at postnatal of 14 days and 30 days in wild-type mice. The mice (8 weeks) were either sham operated or ovariectomy (OVX) and then sacrificed at 2, 4 and 8 w. The GP were stained by Movat staining, and mSSC lineage was analyzed. Then, mSSCs were sorted by fluorescence-activated cell sorting (FACS); the clonal ability, chondrogenic differentiation and osteogenic differentiation were evaluated, and the changed genes were analyzed by RNA-seq. RESULTS: The percentage of mSSCs were decreased with the narrow GP. Heights of GP were decreased significantly in 8w-ovx mice compared with 8w-sham mice. We found the percentage of mSSCs were decreased in mice at 2w after ovx, but the cell numbers were not changed. Further, the percentage and cell numbers of mSSCs were not changed at 4w and 8w after ovx. Importantly, the clonal ability, chondrogenic differentiation and osteogenic differentiation of mSSCs were impaired at 8w after ovx. We found 114 genes were down-regulated in mSSCs, including skeletal developmental genes such as Col10a1, Col2a1, Mef2c, Sparc, Matn1, Scube2 and Dlx5. On the contrary, 526 genes were up-regulated, including pro-inflammatory genes such as Csf1, Nfkbla, Nfatc2, Nfkb1 and Nfkb2. CONCLUSION: Function of mSSCs was impaired by up-regulating pro-inflammatory genes in ovx-induced osteoporosis.

[Evaluation of peripheral blood T-lymphocyte subpopulations features in patients with hepatitis B virus-related acute-on-chronic liver failure based on single-cell sequencing technology].

Objective: T lymphocyte exhaustion is an important component of immune dysfunction. Therefore, exploring peripheral blood-exhausted T lymphocyte features in patients with hepatitis B virus-related acute-on-chronic liver failure may provide potential therapeutic target molecules for ACLF immune dysfunction. Methods: Six cases with HBV-ACLF and three healthy controls were selected for T-cell heterogeneity detection using the single-cell RNA sequencing method. In addition, exhausted T lymphocyte subpopulations were screened to analyze their gene expression features, and their developmental trajectories quasi-timing. An independent sample t-test was used to compare the samples between the two groups. Results: Peripheral blood T lymphocytes in HBV-ACLF patients had different differentiation trajectories with different features distinct into eight subpopulations. Among them, the CD4(+)TIGIT(+) subsets (P = 0.007) and CD8(+)LAG3(+) (P = 0.010) subsets with highly exhausted genes were significantly higher than those in healthy controls. Quasi-time analysis showed that CD4(+)TIGIT(+) and CD8(+)LAG3(+) subsets appeared in the late stage of T lymphocyte differentiation, suggesting the transition of T lymphocyte from naïve-effector-exhausted during ACLF pathogenesis. Conclusion: There is heterogeneity in peripheral blood T lymphocyte differentiation in patients with HBV-ACLF, and the number of exhausted T cells featured by CD4(+)TIGIT(+)T cell and CD8(+)LAG3(+) T cell subsets increases significantly, suggesting that T lymphocyte immune exhaustion is involved in the immune dysfunction of HBV-ACLF, thereby identifying potential effective target molecules for improving ACLF patients' immune function.

[Research progress of anti-fibrotic drugs that inhibit epithelial-mesenchymal transition in pulmonary fibrosis].

Pulmonary fibrosis is the end-stage pathological change of lung diseases, which seriously affects the respiratory function of human body. A large number of studies at home and abroad have confirmed that epithelial-mesenchymal transition (EMT) is an important intermediate stage in the development of pulmonary fibrosis. Inhibition of multiple pathways upstream and downstream of EMT, such as the classical Smads pathway and non-Smads pathway of TGF-1 can effectively inhibit the process of EMT and alleviate pulmonary fibrosis. This article will review the main conclusions of the mechanism of action of EMT as a target to improve the pathology of pulmonary fibrosis so far, and provide a theoretical basis and research direction for further research and development of anti-pulmonary fibrosis drugs.

Chondrocyte apoptosis in temporomandibular joint osteoarthritis promotes bone resorption by enhancing chemotaxis of osteoclast precursors.

OBJECTIVE: This study aimed to explore the effect and mechanism of chondrocyte apoptosis on the chemotaxis of osteoclast precursors (OCPs) during bone destruction. DESIGN: The relationship between cartilage and bone destruction was verified with a rat temporomandibular joint osteoarthritis (TMJOA) model. The pan-caspase inhibitor Z-VAD-FMK (ZVAD) was applied to confirm the chemotactic effect of chondrocyte apoptosis on OCPs. Synthesis and release of the key chemokine CX3CL1 in apoptotic and non-apoptotic chondrocytes was assessed with IHC, IF, WB, and ELISA. The function of CX3CL1-CX3CR1 axis in the chemotaxis of OCPs was examined by CX3XR1 inhibitor AZD8797 (AZD) and si-CX3CL1. The regulatory effect of p38 MAPK on CX3CL1 release was verified by p38 inhibitor PH-797804. RESULTS: A temporal and spatial association between cartilage degradation and bone resorption was found in the TMJOA model. The caspase-dependent chondrocyte apoptosis promoted chemotaxis of OCPs, which can be restrained by ZVAD. CX3CL1 was significantly upregulated when chondrocytes underwent apoptosis, and it played a critical role in the recruitment of OCPs, blockage of CX3CL1-CX3CR1 axis resulted in less bone resorption in TMJOA. P38 MAPK was activated in apoptotic chondrocytes, and had a regulatory effect on the synthesis and release of CX3CL1. After inhibition of p38 by PH-797804, the chemotactic effect of apoptotic chondrocytes on OCPs was limited. CONCLUSIONS: This study indicates that apoptosis of chondrocytes in TMJOA enhances chemotaxis of OCPs toward osteoclast precursors through upregulation of the p38-CX3CL1 axis, thereby promoting the activation of local osteoclasts.

Efficient high-charge Laguerre-Gaussian mode conversion by using a periscopic axicon mirror.

Laguerre-Gaussian (LG) modes can be converted from fundamental Gaussian mode by using phase optical elements such as spiral phase plates (SPP), but the conversion efficiency is strongly reduced in high charge plates because of the transverse intensity deviation. In this paper, a three-step scheme is proposed to dramatically improve the conversion efficiency. First, a fundamental Gaussian beam is converted to a 1st-order LG beam via a 1st-order SPP and a spatial filtering system. Then, by using a periscopic axicon mirror (PAM), the lst-order LG beam is transformed into an annular beam with larger beam radius. Finally, by using a second high-order SPP, this intensity-matched ring beam can be effectively converted to a high-charge LG0l beam. Through optimization of the PAM's parameter, the total conversion efficiency from fundamental Gaussian beam to LG0l mode as high as 91.85% is obtained, which is much higher than the case without PAM. Numerical simulations are carried out by the particle-in-cell (PIC) code EPOCH to verify the effectiveness of the scheme.

[Diagnostic values of urinary citrate for kidney stones in patients with primary gout].

OBJECTIVE: To evaluate the relationship between 24 h urinary ion content and kidney stones, and to explore the diagnostic values of kidney stone in primary gout patients. METHODS: Patients diagnosed with primary gout had ultrasound scanning of both feet and kidneys in Peking University First Hospital from Jan. 2020 to May 2021. Their clinical characteristics were compared between the positive and negative kidney stone groups, and the relationship between kidney stone and urinary ion composition were analyzed. Risk factors of kidney stone were analyzed. The explored diagnostic values were evaluated for urinary oxalate and citrate according with uric acid kidney stones by dual-energy computed tomography (DECT). RESULTS: Among the 100 gouty patients, 80 patients had uric acid crystal deposition in lower joints of extremity by ultrasonography, 61 patients had kidney stone, and 34 had kidney uric acid stones by DECT. All the multiple kidney stones were proved as uric acid kidney stones by DECT. Compared with patients without kidney stone group proved by ultrasonography, patients with kidney stone had longer gouty duration [(48.7±26.6) months vs. (84.0±30.6) months, P=0.01], higher 24 h urinary oxalate [(20.1±9.6) mg vs. (28.6±20.7) mg, P=0.001] and lower 24 h urinary citrate [(506.3±315.4) mg vs. (355.7±219.6) mg, P=0.001]. Compared with the patients without kidney stone by DECT, the patients with uric acid kidney stone also had longer disease duration [(49.1±28.4) months vs. (108.3±72.2) months, P=0.001], higher 24 h urinary oxalate [(23.6±16.9) mg vs. (28.5±18.8) mg, P < 0.05], lower 24 h urinary citrate [(556.0±316.3) mg vs. (391.7±261.2) mg, P < 0.05], higher serum uric acid [(466.2±134.5) µmol/L vs. (517.2±18.1) µmol/L, P < 0.05] and higher 24 h urinary uric acid [(1 518.1±893.4) mg vs. (1 684.2±812.1) mg, P < 0.05]. Logistic regression analysis showed long gout disease duration (OR=1.229, 95%CI: 1.062-1.522, P < 0.05), high serum uric acid level (OR=1.137, 95%CI: 1.001-1.213, P=0.01), low 24 h urinary citrate (OR=0.821, 95%CI: 0.659-0.952, P=0.01) were all risk factors of kidney stones by ultrasonography. Also, long gout disease duration (OR=1.201, 95%CI: 1.101-1.437, P=0.005), high serum creatine uric level (OR=1.145, 95%CI: 1.001-1.182, P=0.04), low 24 h urinary citrate (OR=0.837, 95%CI: 0.739-0.931, P=0.02) were all risk factors of kidney uric acid stones by DECT. CONCLUSION: Long disease duration and low 24 h urinary citrate were risk factors for kidney stones.

[Progress in preserved ratio impaired spirometry].

Preserved ratio impaired spirometry (PRISm) refers to the mode of a decrease in forced expiratory volume in 1 second (FEV1) while the FEV1/forced vital capacity (FVC) remains constant. PRISm was prevalent in the study population, but it is underreported in the current research. The cohort studies in European-American have found that the PRISm has a higher risk of developing chronic obstructive pulmonary disease (COPD), cardiovascular-related deaths and all-causes death than the normal lung function. PRISm may be one of the pre-COPD population, so early detection and prevention are crucial. In this review, we summarized the recent advances in the research of PRISm with the aim to increase understanding of PRISm, and to provide comprehensive evaluation and management for PRISm population.

Interleukin-35 has a tumor-promoting role in hepatocellular carcinoma.

Hepatic inflammatory response is a risk factor for liver cancer initiation and progression. Interleukin (IL)-35 is the newest member of the IL-12 cytokine family, and has been reported to play an essential role in the immunosuppressive liver microenvironment. Herein we focus on the expression profiles of IL-35 in hepatocellular carcinoma (HCC) and effects on local immune status. HCC transcriptome array data were downloaded from Gene Expression Omnibus (GEO). Analysis was performed by BRB-Array Tools and Ingenuity Pathway Analysis (IPA) software. Serum IL-35 level was detected by AimPlet bead-based immunoassay. In-situ IL-35 detection was performed by immunohistochemical staining and Western blot. The n-vitro effect of IL-35 on CD4+ or CD8+ T cell function was detected by flow cytometry. Our results showed that there were large amounts of IL-35 expressed in HCC serum and tumor tissues. IL-35 expression affects the transcript of thousands of genes, most differentially expressed genes (DEGs), in tumor tissues correlated with T cell immunity. The IL-35 high-expression group exhibited enhancement of regulatory T cells (Tregs ) and impairment of cytolytic T cells. In-vitro experiments proved that exogenous IL-35 stimulated the expression of programmed cell death 1 (PD-1) and lymphocyte activation gene-3 (LAG3) in CD4+ and CD8+ T cells. In addition, the stimulating effect was time-dependent. Furthermore, IL-35 inhibited interferon (IFN)-γ secretion by CD4+ and CD8+ T cells. Elevated IL-35 had an immune suppressive role in HCC tumor microenvironments through affecting inhibitor receptor expression and cytokine secretion of CD4+ and CD8+ T cells. Dissection of the precise targets and underlying molecular mechanisms would mean alternative treatments for HCC patients.

microRNA-29b mediates Th17/Treg imbalance in chronic obstructive pulmonary disease by targeting IL-22.

Chronic obstructive pulmonary disease (COPD) represents a chronic inflammatory disorder of the airways induced mainly by cigarette smoking. In the current study, cigarette smoke extract (CSE) was used to develop an in vitro COPD model using human bronchial epithelium (HBE) cells to expound the possible role of microRNA-29b (miR-29b) in COPD. Firstly, miR-29b and interleukin (IL)-22 expression was assessed in serum of 20 healthy non-smokers, 20 healthy smokers and 20 COPD patients as well as CSE-treated HBE cells. Then, miR-29b and IL-22 expression was altered to evaluate their functions in Th17/Treg ratio. miR-29b inhibited Th17/Treg ratio and levels of IL-22; whereas overexpression of IL-22 reversed these trends. Moreover, rescue experiments found that IL-22 neutralized the repressive effects of miR-29b on Th17/Treg ratio and inflammatory response. Finally, we found that miR-29b blocked the JAK/STAT3 pathway in CSE-treated HBE cells. These data highlighted that miR-29bs modulated Th17/Treg imbalance in CSE-induced experimental COPD through inhibition of IL-22-dependent JAK/STAT3 pathway.

[Quantitative myocardial perfusion parameters in subjects without coronary artery lesions based on computed tomography dynamic myocardial perfusion imaging].

Objective: To determinate the range of quantitative myocardial perfusion parameters (MBF, MBV) in subjects without coronary artery lesions by dynamic computed tomography myocardial perfusion imaging (CTP). Methods: Subjects with occasional chest tightness or family history of coronary artery disease coming to Fuwai Hospital underwent coronary computed tomography angiography (CCTA) were prospectively enrolled. A total of 34 subjects [mean age (50±7) years, range from 33 to 65 years; 15 male and 19 female] were enrolled. Coronary lesions were not confirmed in any subjects using CCTA and volunteered for stress and rest dynamic CTP examination. MBF and MBV values were calculated in each myocardial segment using a 17-segment model. The global ranges of MBF and MBV were analyzed, and the gender variability and regional variability were compared. Results: The mean global MBF and MBV at rest and under stress were (115.5±27.4) ml·100 g-1·min-1, (212.8±40.8) ml·100 g-1·min-1 and (17.6±4.0) ml/100 g, (25.8±4.6) ml/100 g, respectively. The absolute and resolute reserves of MBF and MBV [(102.8±41.5) ml·100 g-1·min-1, 107.7%±52.5%; (9.3±5.2) ml/100 g, 62.1%±47.4%] were highest in the right coronary artery territory, but without any significant differences. The stress MBF and absolute reserve of MBF in females were higher than those of males [(228.6±39.9) ml·100 g-1·min-1, (113.3±46.2) ml·100 g-1·min-1; (192.8±33.4) ml·100 g-1·min-1, (77.0±41.2) ml·100 g-1·min-1] (both P<0.05). The MBF resolute reserve, rest MBV, stress MBV and MBV absolute and resolute reserves were higher in females, but without significant differences (all P>0.05). Conclusion: The mean global MBF and MBV at rest and under stress were (115.5±27.4) ml·100 g-1·min-1, (212.8±40.8) ml·100 g-1·min-1 and (17.6±4.0) ml/100 g, (25.8±4.6) ml/100 g. The MBF under stress perfusion and MBF absolute reserve of females are higher than those of males.

Exacerbations of Severe Asthma While on Anti-IL-5 Biologics.

Anti-interleukin 5 (IL-5) and anti-IL-5 receptor α monoclonal antibodies markedly decrease airway and peripheral blood eosinophil numbers and are thus highly effective in reducing asthma exacerbations. Nonetheless, these biologics do not completely resolve exacerbations. There is very little information on the cellular nature of exacerbations during treatment with biologics. Using illustrative clinical case scenarios, we highlight the importance of carefully characterizing asthmatics at the time of exacerbation and recognizing neutrophilic causes of exacerbations to ensure optimal management. While an eosinophilic exacerbation may improve with more corticosteroids or by switching to another anti-IL-5 monoclonal antibody, a noneosinophilic exacerbation will likely not. An infective exacerbation needs to be recognized, and the pathogen must be identified and treated with the appropriate antimicrobial agent.

[Predictive value of vascular health indicators on newly cardiovascular events: Preliminary validation of Beijing vascular health stratification system].

OBJECTIVE: To explore the predictive value of carotid femoral artery pulse wave velocity (CF-PWV), carotid radial artery pulse wave velocity (CR-PWV), cardio-ankle vascular index (CAVI), and ankle brachial index (ABI) on coronary heart disease (CHD) and cerebral infarction (CI), and the preliminary validation of Beijing vascular health stratification (BVHS). METHODS: Subjects with at least 2 in-patient records were included into the study between 2010 and 2017 from Vascular Medicine Center of Peking University Shougang Hospital. Subjects with CHD or CI, and without data of vascular function at baseline were excluded. Eventually, 467 subjects free of CHD [cohort 1, mean age: (63.4±12.3) years, female 42.2%] and 658 subjects free of CI [cohort 2, mean age: (64.3±12.2) years, female 48.7%] at baseline were included. The first in-patient records were as the baseline data, the second in-patient records were as a following-up data. Cox proportional hazard regression was used to establish the predictive models of CHD or CI derived from BVHS by multivariable-adjusted analysis. RESULTS: The median follow-up time of cohort 1 and cohort 2 was 1.9 years and 2.1 years, respectively. During the follow-up, 164 first CHD events occurred in cohort 1 and 117 first CI events occurred in cohort 2. Four indicators were assessed as continuous variables simultaneously by multivariable-adjusted analysis. In cohort 1, CF-PWV, CR-PWV, ABI, and CAVI reached statistical significance in the multivariable-adjusted models (P<0.05). In cohort 2, only CAVI (P<0.05) was of statistical significance. In addition, the higher CF-PWV became a protector of CHD or CI (P<0.05). The prediction value of BVHS reached the statistical significance for CHD and CI in the unadjusted models (all P<0.05), however, BVHS could only predict the incidence of CHD (P<0.05), but not the incidence of CI (P>0.05) in the multivariable-adjusted models. CF-PWV, CR-PWV, ABI, and CAVI were associated factors of CHD independent of each other (P<0.05), only CAVI (P<0.05) was the risk factor of CI independent of the other three. CONCLUSION: The different vascular indicators might have different effect on CHD or CI. CAVI might be a stable predictor of both CHD and CI. Higher baseline CF-PWV was not necessarily a risk factor of CHD or CI because of proper vascular health management. BVHS was a potential factor for the prediction of CHD, and further research is needed to explore the prediction value for CI.

[Research progress on the occurrence and prevention of low back pain in naval officers and soldiers].

Low back pain (LBP) is a common occupational disease among naval officers and soldiers. This article reviewed the incidence of LBP in naval personnel in different positions in recent years, and analyzed the causes combined with the operating environment and occupational characteristics of personnel in different positions in order to clarify the causes of LBP in naval officers and soldiers in different positions and improve their awareness of the disease. Moreover, this study aims to help naval officers and soldiers to take protective measures in training life to reduce the incidence of LBP.

[Construction of disease assessment index of silicosis patients].

Objective: To explore the establishment of disease assessment index model in silicosis patients. Methods: In October 2018, 171 silicosis patients who were hospitalized from November 2014 to November 2015 were selected as the study subjects. According to the standard of death risk, the subjects were divided into two groups, including the group without death risk (153 cases) and the group with death risk (18 cases) . Through literature analysis and clinical experience, the variables related to silicosis were preliminarily screened. Multifactorial logistic regression analysis variables were used to analyze the relationship between the variables and the risk of death. The variables associated with the risk of death were selected as the final variables to establish the disease assessment index model. And the receiver operating characteristic (ROC) curve was used to evaluate the clinical application of the disease assessment index. Results: Five variables of Modified British Medical Research Council Respiratory Questionnaire (mMRC) , pulmonary function injury, pneumoconiosis stage, aggravation of the disease and complications were selected as the variables of the disease assessment index, and the assessment index score ranged from 1 to 11 points. The area under the ROC curve of disease assessment index was 0.747 (95%CI: 0.590-0.904) , which could better identify the death risk of silicosis patients. With the increase of disease assessment index score, the death risk of silicosis patients increased. When the cutoff value was 7, the sensitivity and specificity were 0.667 and 0.876, respectively, for the risk of death of silicosis patients. The results of cross-validation showed that the correct discrimination rate of the disease assessment index to the risk of death was 66.7%. Conclusion: The disease assessment index can predict the death risk of patients with silicosis, and can evaluate the disease comprehensively.