Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response.

The role of innate immune cells in allergen immunotherapy that confers immune tolerance to the sensitizing allergen is unclear. Here, we report a role of interleukin-10-producing type 2 innate lymphoid cells (IL-10+ ILC2s) in modulating grass-pollen allergy. We demonstrate that KLRG1+ but not KLRG1- ILC2 produced IL-10 upon activation with IL-33 and retinoic acid. These cells attenuated Th responses and maintained epithelial cell integrity. IL-10+ KLRG1+ ILC2s were lower in patients with grass-pollen allergy when compared to healthy subjects. In a prospective, double-blind, placebo-controlled trial, we demonstrated that the competence of ILC2 to produce IL-10 was restored in patients who received grass-pollen sublingual immunotherapy. The underpinning mechanisms were associated with the modification of retinol metabolic pathway, cytokine-cytokine receptor interaction, and JAK-STAT signaling pathways in the ILCs. Altogether, our findings underscore the contribution of IL-10+ ILC2s in the disease-modifying effect by allergen immunotherapy.

DJ-1 depletion prevents immunoaging in T-cell compartments.

Decline in immune function during aging increases susceptibility to different aging-related diseases. However, the underlying molecular mechanisms, especially the genetic factors contributing to imbalance of naïve/memory T-cell subpopulations, still remain largely elusive. Here, we show that loss of DJ-1 encoded by PARK7/DJ-1, causing early-onset familial Parkinson's disease (PD), unexpectedly diminished signs of immunoaging in T-cell compartments of both human and mice. Compared with two gender-matched unaffected siblings of similar ages, the index PD patient with DJ-1 deficiency showed a decline in many critical immunoaging features, including almost doubled non-senescent T cells. The observation was further consolidated by the results in 45-week-old DJ-1 knockout mice. Our data demonstrated that DJ-1 regulates several immunoaging features via hematopoietic-intrinsic and naïve-CD8-intrinsic mechanisms. Mechanistically, DJ-1 depletion reduced oxidative phosphorylation (OXPHOS) and impaired TCR sensitivity in naïve CD8 T cells at a young age, accumulatively leading to a reduced aging process in T-cell compartments in older mice. Our finding suggests an unrecognized critical role of DJ-1 in regulating immunoaging, discovering a potent target to interfere with immunoaging- and aging-associated diseases.

Longitudinal evaluation of cervical length and shear wave elastography in women with spontaneous preterm birth.

OBJECTIVE: To evaluate longitudinal changes in cervical length (CL) and mean cervical shear wave elastography (CSWE) score in women with a singleton or twin pregnancy who undergo spontaneous preterm birth (sPTB) compared with those who deliver at term. METHODS: This was a prospective longitudinal study of unselected women with a singleton or twin pregnancy attending a dedicated research clinic for screening for sPTB at four timepoints during pregnancy: 11 + 0 to 15 + 6 weeks, 16 + 0 to 20 + 6 weeks, 21 + 0 to 24 + 6 weeks and 28 + 0 to 32 + 6 weeks. At each visit, a transvaginal ultrasound scan was conducted to measure the CL and the CSWE scores in six regions of interest (ROI) (inner, middle and external parts of anterior and posterior cervical lips). The mean CSWE score from the six ROIs was calculated for analysis. Log10 transformation was applied to data to produce a Gaussian distribution prior to statistical analysis. A multilevel mixed-effects analysis was performed to compare longitudinally CL and CSWE between the sPTB and term-delivery groups. RESULTS: The final cohort consisted of 1264 women, including 1143 singleton pregnancies, of which 57 (5.0%) were complicated by sPTB, and 121 twin pregnancies, of which 33 (27.3%) were complicated by sPTB. Compared to those who delivered at term, women with sPTB had a lower CL across gestation when controlling for history of cervical surgery, number of fetuses, gestational age (GA) at cervical assessment and the interaction between GA at cervical assessment and sPTB (P < 0.001). Specifically, CL in the sPTB group was significantly lower at 21 + 0 to 24 + 6 weeks (P = 0.039) and 28 + 0 to 32 + 6 weeks (P < 0.001). Twin pregnancies had significantly greater CL throughout pregnancy compared with singleton pregnancies (regression coefficient, 0.01864; P < 0.001). After adjusting for maternal age, weight, height, body mass index and GA at cervical assessment, CSWE score in the sPTB group was significantly lower compared with that in the term-delivery group across gestation (P = 0.013). However, on analysis of individual visits, CSWE score in the sPTB group was significantly lower than that in the term-delivery group only at 11 + 0 to 15 + 6 weeks (P = 0.036). There was no difference in CSWE score between singleton and twin pregnancies throughout gestation (regression coefficient, -0.00128; P = 0.937). CONCLUSIONS: Women with sPTB have a shorter and softer cervix across gestation compared with those who deliver at term. A shorter cervix in the sPTB group is observed from the late second trimester onwards, while lower cervical stiffness in the sPTB group is observed primarily in the first trimester. CL is significantly lower in singleton pregnancies compared with twin pregnancies, while cervical stiffness does not differ between the two. Our findings indicate that the cervix tends to undergo a softening process prior to shortening in sPTB cases. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

[Dyspnea with multiple bilateral lung opacities on CT scan].

A 58-year-old man was admitted with a typical presentation of acute left heart failure. However, the patient showed a partial response to the anti-heart failure therapy. Following admission, a continuous fever was monitored, and a CT scan revealed that multiple opacities on bilateral lungs had progressed. Bronchoscopy was performed, and Coxiella burnetii was detected by Metagenomic next-generation sequencing (mNGS) in bronchoalveolar lavage (BALF), and transbronchial lung biopsy showed organizing pneumonia. Considering that the patient had a history of rabbit breeding and delivery, with some newborn rabbits dying before he became ill, organizing pneumonia secondary to Q fever pneumonia was diagnosed. Anti-Q fever treatment was initiated and the patient's temperature returned to normal. Glucocorticoid was administered after adequate treatment for Q fever. The patient's symptom of dyspnea relieved soon and opacities on CT scan were absorbed remarkably. The final diagnosis was organizing pneumonia secondary to Q fever pneumonia accompanied with left heart failure.

[Analysis of pre-operative factors affecting vault after posterior chamber phakic intraocular lens implantation].

Objective: To analyze the early changes in vault height and its influencing factors after implantation of posterior chamber phakic intraocular lenses (pIOL). Methods: A retrospective case series study was conducted, including patients who underwent pIOL implantation at Zhongshan Ophthalmic Center, Sun Yat-sen University, from September 2020 to August 2021, and completed a 3-month follow-up. Data were collected from myopic or myopic astigmatism patients. Preoperative ocular examinations, including Pentacam anterior segment analysis system, Sirius anterior segment analysis system, ultrasound biomicroscopy (UBM), and IOLMaster optical biometry, were performed to measure parameters such as refractive power, corneal curvature, corneal horizontal diameter, anterior chamber volume, anterior chamber depth, pupil diameter, sulcus-to-sulcus diameter (STS), and lens thickness. The degree and position of implanted pIOL, as well as vault height measured by anterior segment optical coherence tomography (AS-OCT) at 1 day, 1 week, 1 month, and 3 months postoperatively, were recorded. Statistical analyses were conducted using repeated measures analysis of variance, Pearson correlation analysis, and multiple linear regression analysis. Results: A total of 314 patients (314 eyes) were included, with 52 male (16.56%) and 262 female (83.44%) patients, and an average age of (26.44±4.60) years. The preoperative equivalent spherical power was (-8.09±2.41) D. Postoperative vault heights at 1 day, 1 week, 1 month, and 3 months were (671.88±273.02) µm, (652.26±272.21) µm, (615.08±259.69) µm, and (591.14±250.71) µm, respectively, with statistically significant differences among groups (P<0.001). Eyes with vault height>750 µm showed a greater decrease in early postoperative vault height (P<0.001). The eyes implanted with 12.1 mm pIOL had the lowest postoperative vault height, while those with 13.2 mm had the highest (P>0.05). Factors correlated with vault height at 1 day postoperatively included corneal horizontal diameter, anterior chamber depth, preoperative cylinder power, angle degree, lens thickness, and pIOL cylinder power. Factors correlated with vault height at 3 months postoperatively included corneal horizontal diameter, anterior chamber depth, preoperative cylinder power, anterior chamber volume, angle degree, lens thickness, axial length, pIOL spherical and cylinder power. Factors associated with changes in early postoperative vault height included corneal curvature K2, anterior chamber depth, anterior chamber volume, pupil diameter, horizontal STS, vertical STS, axial length, and preoperative spherical power (all P<0.05). Multiple linear regression analysis revealed that lens thickness significantly influenced vault height at 1 day postoperatively, anterior chamber volume significantly influenced vault height at 3 months postoperatively, and pupil diameter significantly influenced changes in early postoperative vault height (all P<0.05). Conclusions: Vault height after pIOL implantation is unstable in the early postoperative period and gradually decreases within 3 months. A higher baseline vault height is associated with a greater decrease. Anterior chamber volume, pupil diameter, and lens thickness are influencing factors on vault height during the first 3 months postoperatively.

Observation of Monoenergetic Electrons from Two-Pulse Ionization Injection in Quasilinear Laser Wakefields.

The generation of low emittance electron beams from laser-driven wakefields is crucial for the development of compact x-ray sources. Here, we show new results for the injection and acceleration of quasimonoenergetic electron beams in low amplitude wakefields experimentally and using simulations. This is achieved by using two laser pulses decoupling the wakefield generation from the electron trapping via ionization injection. The injection duration, which affects the beam charge and energy spread, is found to be tunable by adjusting the relative pulse delay. By changing the polarization of the injector pulse, reducing the ionization volume, the electron spectra of the accelerated electron bunches are improved.

Evaluation of the allocation efficiency of medical and health resources in China's rural three-tier healthcare system.

OBJECTIVES: Evaluating the efficiency of health resource allocations is critical to improving China's rural three-level health service network. STUDY DESIGN: This was a prospective panel data study. METHODS: Based on panel data of the medical and health resources of 31 provinces within rural China, collected from 2003 to 2020, this study uses a three-stage Data Envelopment Analysis-Malmquist index to analyze the evolution of efficiency and productivity. RESULTS: The efficiency and productivity of county and county-level medical and health institutions rank highest, followed by township hospitals, whereas village clinics are shown to be in great need of improvement. A decline in technical advancement appears as a crucial factor exacerbating loss of factor productivity. CONCLUSIONS: Policy makers should further optimize the efficiency of medical resource allocation and promote the coordinated development of rural health in China.

[Application of Rotarex catheter system in femoropopliteal artery stenosis accompanied with thrombosis].

OBJECTIVE: To evaluate the effectiveness and safety of Rotarex catheter system in treating femoropopliteal artery stenosis accompanied with thrombosis. METHODS: From Jun. 2017 to Dec. 2019, the clinical data of 32 femoropopliteal artery stenosis accompanied with thrombosis cases treated with Rotarex catheter system were retrospectively analyzed. There were 23 males and 9 females aged from 50 to 89 years and the mean age was (70.7±10.3) years. Six cases had acute course of disease (≤2 weeks), 17 cases had subacute course of disease (>2 weeks, ≤3 months), and 9 cases had chronic course of disease (>3 months). Mean lesion length was (23.4±13.7) cm, mean occlusion length was (19.9±13.3) cm, and in-stent occlusion 7 cases. The superficial femoral artery (SFA) was involved in 13 cases, the popliteal artery (PA) was involved in 8 cases, and both SFA and PA were involved in the other 11 cases. All the cases were treated with Rotarex catheter system. When necessary, suction with large lumen catheter was enabled. Residual stenosis was treated with percutaneous transluminal angioplasty (PTA). Drug-coated balloon (DCB) was only used in patients with financial status, and stent was used only when it was necessary. Heparin was used for 24 h after procedures, and after that, antiplatelet agents were used. Doppler ultrasonography was taken during the followed-up. RESULTS: Technical success was 100%, and mean procedure time was (107.4±21.5) min. 8F (1F≈0.33 mm) and 6F Rotarex catheter were used in 27 and 5 cases respectively. In 27 cases, forward flow was obtained immediately after debulking with Rotarex catheter, and in the other 5 cases, suction with large lumen catheters were used. PTA was used in all 32 cases. DCB were used in 8 cases, of which 4 were used in in-stent stenosis. Twelve cases were implanted stents. There were no perioperative deaths. The only one procedure related complication was distal embolism. We took out the thrombus with guiding catheter. In all cases, mean hospital stay were (4.6±1.5) d. The ankle brachial index increased from 0.32±0.15 to 0.86±0.10 after treatment (t=-16.847, P < 0.001). The Rutherford stages decreased significantly (Z=-4.518, P < 0.001). All the patients were followed up for 6.0-36.0 months, and the median time was 16.0 months. 2 cases stopped antiplatelet agents, which resulted in acute thrombosis. Another percutaneous mechanical thrombectomy and PTA were taken in one of them. Two cases died of cardiovascular disease during the follow-up, and no amputation was observed. Target lesion restenosis occurred in 7 cases during the follow-up, and target lesion revascularization (TLR) was taken in two of them. CONCLUSION: In treating femoropopliteal artery stenosis accompanied with thrombosis, Rotarex catheter can remove thrombus effectively, and that can expose underlying lesions and reduce stent use and complications rates. It is a safe and effective method.

Stress hormone signalling inhibits Th1 polarization in a CD4 T-cell-intrinsic manner via mTORC1 and the circadian gene PER1.

Stress hormones are believed to skew the CD4 T-cell differentiation towards a Th2 response via a T-cell-extrinsic mechanism. Using isolated primary human naïve and memory CD4 T cells, here we show that both adrenergic- and glucocorticoid-mediated stress signalling pathways play a CD4 naïve T-cell-intrinsic role in regulating the Th1/Th2 differentiation balance. Both stress hormones reduced the Th1 programme and cytokine production by inhibiting mTORC1 signalling via two parallel mechanisms. Stress hormone signalling inhibited mTORC1 in naïve CD4 T cells (1) by affecting the PI3K/AKT pathway and (2) by regulating the expression of the circadian rhythm gene, period circadian regulator 1 (PER1). Both stress hormones induced the expression of PER1, which inhibited mTORC1 signalling, thus reducing Th1 differentiation. This previously unrecognized cell-autonomous mechanism connects stress hormone signalling with CD4 T-cell differentiation via mTORC1 and a specific circadian clock gene, namely PER1.

Prediction of spontaneous preterm birth and preterm prelabor rupture of membranes using maternal factors, obstetric history and biomarkers of placental function at 11-13 weeks.

OBJECTIVES: To determine whether first-trimester biomarkers of placental function can be used to screen for spontaneous preterm birth (sPTB), and to develop prediction models using maternal factors, obstetric history and biomarkers of placental function at 11-13 weeks for the calculation of patient-specific risk for sPTB. METHODS: This was a retrospective secondary analysis of data derived from a prospective cohort study on first-trimester screening for pre-eclampsia in singleton pregnancies attending for routine Down syndrome screening at 11 + 0 to 13 + 6 weeks' gestation at a tertiary obstetric unit between December 2016 and September 2019. A split-sample internal validation method was used to explore and develop prediction models for all sPTB at < 37 weeks and for PTB at < 37 weeks after preterm prelabor rupture of membranes (PPROM) using maternal risk factors, uterine artery Doppler indices, serum placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A) and ß-human chorionic gonadotropin (ß-hCG). Screening performance was assessed using receiver-operating-characteristics (ROC)-curve analysis, with calculation of the areas under the ROC curves (AUCs). RESULTS: A total of 9298 singleton pregnancies were included in this study. sPTB at < 37 weeks occurred in 362 (3.89%) cases, including 231 (2.48%) cases of PPROM. sPTB at < 34 weeks occurred in 87 (0.94%) cases, including 39 (0.42%) cases of PPROM. Identified maternal risk factors for sPTB at < 37 weeks included chronic hypertension, conception using in-vitro fertilization and history of PTB. Maternal risk factors for PPROM at < 37 weeks included conception using in-vitro fertilization and history of PTB. Median PlGF multiples of the median (MoM) and PAPP-A MoM were significantly reduced in women with sPTB at < 37 weeks, as well as in those who had PPROM, compared to those who delivered at term. Screening by a combination of maternal risk factors, PAPP-A and PlGF achieved better performance in predicting sPTB at < 37 weeks (AUC, 0.630 vs 0.555; detection rate (DR), 24.8% vs 16.6% at a false-positive rate (FPR) of 10%; P ≤ 0.0001) and PPROM at < 37 weeks (AUC, 0.643 vs 0.558; DR, 28.1% vs 17.0% at a FPR of 10%; P ≤ 0.0001) than using maternal risk factors alone. Both models were successfully applied to the internal validation dataset, with AUCs of 0.628 and 0.650, respectively. CONCLUSIONS: We demonstrated that low levels of maternal serum PAPP-A and PlGF in the first trimester are associated with increased risks of sPTB and PPROM at < 37 weeks. However, further research is needed to identify additional biomarkers to improve the screening performance of the combined model that includes maternal risk factors, PAPP-A and PlGF before clinical application. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

p120 regulates E-cadherin expression in nasal epithelial cells in chronic rhinosinusitis.

BACKGROUND: The epithelial barrier plays an important role in the regulation of immune homeostasis. The effect of the immune environment on E-cadherin has been demonstrated in previous studies. This discovery prompted new research on the targeting mechanism of E-cadherin in chronic rhinosinusitis (CRS). METHODS: E-cadherin and p120 expression was determined by quantitative RT-PCR, and western blot. The interaction between E-cadherin and p120 was assessed by immunofluorescence staining and coimmunoprecipitation assays. Human nasal epithelial cells (HNECs) were cultured with submerged methods and transfected with p120-specific small interfering RNA. In other experiments, HNECs differentiated with the air-liquid interface (ALI) method were stimulated with various cytokines and Toll-like receptor (TLR) agonists. The barrier properties of differentiated HNECs were determined by assessing fluorescent dextran permeability. RESULTS: E-cadherin and p120 expression was decreased in HNECs from patients with CRS, and the p120 protein expression level was positively correlated with that of E-cadherin. Two isoforms of p120 (p120-1 and p120-3) were expressed in HNECs, with p120-3 being the main isoform. Knocking down p120 in HNECs cultured under submerged conditions significantly reduced the E-cadherin protein expression. The Rac1 inhibitor NSC23766 reversed the protein expression of E-cadherin in p120 knockdown experiments. Inflammatory mediators, including IL-4, TNF-α, TGF- ß, LPS and IFN-Î, reduced E-cadherin and p120 protein expression and increased paracellular permeability. Dexamethasone abolished the downregulation of E-cadherin and p120 caused by inflammatory mediators. CONCLUSIONS: p120 is involved in regulating E-cadherin protein expression in CRS. Dexamethasone may alleviate the reduction in E-cadherin and p120 protein expression caused by inflammatory mediators.

[Long-term outcomes and failure patterns of definitive radiotherapy for cervical esophageal carcinoma].

Objective: To evaluate the long-term outcomes, failure patterns and prognostic factors of definitive radiotherapy in patients with cervical esophageal carcinoma (CEC). Methods: We retrospectively reviewed the clinical data of 148 CEC patients who treated with definitive radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2001 to December 2017. The median radiation dose was 66 Gy (59.4-70 Gy) and 33.1% of patients received concurrent chemotherapy. The Kaplan-Meier method was used to calculate survival rates. The log rank test was used for survival comparison and univariate prognostic analysis. The Cox model was used for multivariate prognostic analysis. Results: The median follow-up time was 102.6 months. The median survival time, 2- and 5-year overall survival (OS) were 22.7 months, 49.9% and 28.3%. The median, 2- and 5-year progression-free survival were 12.6 months, 35.8% and 25.8%. The 2- and 5-year locoregional recurrence-free survival were 59.1% and 50.8%. The 2- and 5-year distant metastases-free survival were 74.6% and 65.9%. Multivariate analysis showed that EQD(2)>66 Gy was the only independent prognostic indicator for OS (P=0.040). The median survival time and 5-year OS rate significantly improved in patients who received EQD(2)>66 Gy than those who received≤66 Gy (31.2 months vs. 19.2 months, 40.1% vs. 19.1%, P=0.027). A total of 87 patients (58.8%) developed tumor progression. There were 50 (33.8%), 23 (15.5%) and 39 (26.4%) patients developed local, regional recurrence and distant metastases, respectively. Eleven patients (7.4%) underwent salvage surgery, and the laryngeal preservation rate for entire group was 93.9%. Conclusions: Definitive radiotherapy is an effective treatment for cervical esophageal carcinoma with the advantage of larynx preservation. Local recurrence is the major failure pattern. EQD(2)>66 Gy is associated with the improved overall survival.

[Application of mechanical debulking in arteriosclerosis occlusive disease of lower extremity].

Objective: To evaluate the effect of mechanical debulking in treating arteriosclerosis occlusive disease of lower extremity. Methods: The clinical data of 52 arteriosclerosis occlusive disease of lower extremity cases treated with Rotarex mechanical debulking system from June 2017 to June 2020 at Department of Intervention Vascular Surgery,Peking University Third Hospital were retrospectively analyzed. There were 37 males and 15 females,aged(69.4±10.1)years(range:47 to 89 years).Lesion length was (21.6±12.9)cm(range:4 to 45 cm),occlusion length was (18.5±11.8)cm(range:4 to 45 cm).The lesion was located in iliac artery(IA) in 6 cases,femoral-popliteal artery(FPA) in 42 cases,and both IA and FPA in 4 cases. All the cases were treated with Rotarex mechanical debulking system. Residual stenosis more than 50% were treated with percutaneous transluminal angioplasty(PTA).Drug coated balloon was used in part of them,and stent was used only when it was necessary. The patient's operation, complications, postoperative target vessel restenosis and reoperation were collected. The paired sample t test and rank sum test was used for data comparison and the postoperative target vessel patency rate was analyzed by Kaplan-Meier survival curve. Results: All the 52 cases obtained technical success. Percutaneous transluminal angioplasty was used in all cases,and drug coated balloon were used in 11 cases. Twenty-six stents were implanted in 24 cases (2 cases implanted 2 stents).Nine stents were implanted in IA and 15 in FPA. The length of stents was (11.3±3.3)cm(range:6 to 23 cm).There were 3 procedure related complications: one of them was acute occlusion in an iliac lesion,and thrombectomy was applied urgently,and the result was good. And the other two were distal embolism. The thrombus were took out with guiding catheter. The hospital stay was (4.8±1.9)days. The ankle brachial index increased from 0.34±0.16 to 0.81±0.16 after treatment(t=-25.160,P<0.01).The Rutherford stages decreased from (M(IQR)) 3(1) to 1(1(Z=-6.825,P<0.01).The median followed up time was 19 months(range:6 to 42 months).Two cases stopped antiplatelet agents during follow-up and which result in acute thrombosis 2 weeks and 2 months later respectively. One of them was treated with percutaneous mechanical thrombectomy and the other one was not for gastrointestinal hemorrhage. Four cases died during follow-up,one case died of lung cancer,one died of abdominal infection,and the other 2 cases died of cardiovascular disease,and no amputation was observed. Target lesion restenosis(TLR) more than 50% occurred in 13 cases during the follow-up. All TLR were observed in FPA,and target lesion revascularization was taken in 3 of them. According to Kaplan-Meier survival curve analysis,half-year,1-year and 2-year cumulative patency rates of target vessels in this group was 94.2%,87.4% and 51.4%, respectively. And half-year and 1-year cumulative patency rates just in FPA cases was 92.9% and 84.3%, respectively. Conclusions: Percutaneous mechanical debulking using Rotarex catheter combining PTA can reduce the use of stents in femoral-popliteal artery. It is safe and effective in treating with arteriosclerosis obliterans of lower extremity.

Application of artificial intelligence in diagnosis of osteoporosis using medical images: a systematic review and meta-analysis.

Artificial intelligence (AI) is a potentially reliable assistant in the diagnosis of osteoporosis. This meta-analysis aims to assess the diagnostic accuracy of the AI-based systems using medical images. We searched PubMed and Web of Science from inception to June 15, 2020, for eligible articles that applied AI approaches to diagnosing osteoporosis using medical images. Quality and bias of the included studies were evaluated with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The main outcome was the sensitivity and specificity of the performance of the AI-based systems. The data analysis utilized the R Foundation packages of "meta" for univariate analysis and Stata for bivariate analysis. Random effects model was utilized. Seven studies with 3186 patients were included in the meta-analysis. The overall risk of bias of the included studies was assessed as low. The pooled sensitivity was 0.96 (95% CI 0.93-1.00), and the pooled specificity was 0.95 (95% CI 0.91-0.99). However, high heterogeneity was found in this meta-analysis. The results supported that the AI-based systems had good accuracy in diagnosing osteoporosis. However, the high risk of bias in patient selection and high heterogeneity in the meta-analysis made the conclusion less convincing. The application of AI-based systems in osteoporosis diagnosis needs to be further confirmed by more prospective studies in multi-centers including more random samples from complete patient types.

High cyclic tensile stress disrupts the extracellular matrix in human chondrocyte by F-actin cytoskeletal polymerization and reactive oxygen species production.

This study aims to explore the mechanism of cyclic tensile stress (CTS) on human chondrocytes (CHs) relating to the reactive oxygen species (ROS) generation and extracellular matrix (ECM) stability in vitro. A well-established CTS model with 5%, 10%, or 20% elongation was performed for CHs stretching. After CTS, the cell viability, total ROS level, main ECM components, matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP), F-actin density, and some anti-oxidative enzymes were analyzed. Additionally, the antioxidant N-acetylcysteine (NAC) and cytochalasin D were used to suppress the ROS production and F-actin polymerization when the CHs underwent CTS, respectively. The treatment of 20% elongation-CST significantly decreased the CH viability and the expressions of collagen II, aggrecan, anti-oxidative enzymes and TIMP3/4, however, it increased the ROS accumulation, F-actin polymerization, and the expression of collagen I and MMP3/13. In contrast, the application of NAC and cytochalasin D could partly rescue the CHs from the injury caused by the high CTS. Therefore, high CTS disrupts the ECM by remodeling the F-actin cytoskeleton and promoting ROS production. Cytochalasin D and NAC are effective in rejecting F-actin cytoskeleton polymerization, and ROS accumulation through a potential synergetic process, which alleviates the ECM injury caused by High CTS.

Mechanism of MIR-210 mediated NF-κB pathway on cardiac ischemia-reperfusion injury.

In this study, MicroRNA-210 (miR-210), which was previously proved to be a potential immunomodulator in various disease, attenuated mouse myocardium ischemia/reperfusion (I/R) injury. miR-210 was increased in cardiomyocytes exposed to hypoxia/reoxygenation (H/R). The expression of IL-6 and TNF-α in both serum and supernatant were reduced in miR-210 mimics groups. Mice were randomly divided into four groups, which were pre-treated with saline (sham and ischemia/reperfusion group), miR-210 mimics and miR-210 inhibitor treatments. Three days later, the mouse IR model was established by ischemia for 30 min, followed by reperfusion for 3 h. Myocardium and plasma were harvested and assessed. The myocardium histopathological changes were reduced in miR-210 mimics groups, and serum levels of Creatine kinase isoenzyme (CK-MB) and Lactate dehydrogenase (LDH) were significantly decreased compared with I/R groups. The protein expression of proinflammatory factor interleukin (IL)-1ß and IL-6 were suppressed by the up-regulation of miR-210. The expression of miR-210 was negatively correlated with the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). In conclusion, our study indicates that miR-210 protects heart from myocardium I/R injury via suppressing NF-κB signal pathway.

The most incompressible metal osmium at static pressures above 750 gigapascals.

Metallic osmium (Os) is one of the most exceptional elemental materials, having, at ambient pressure, the highest known density and one of the highest cohesive energies and melting temperatures. It is also very incompressible, but its high-pressure behaviour is not well understood because it has been studied so far only at pressures below 75 gigapascals. Here we report powder X-ray diffraction measurements on Os at multi-megabar pressures using both conventional and double-stage diamond anvil cells, with accurate pressure determination ensured by first obtaining self-consistent equations of state of gold, platinum, and tungsten in static experiments up to 500 gigapascals. These measurements allow us to show that Os retains its hexagonal close-packed structure upon compression to over 770 gigapascals. But although its molar volume monotonically decreases with pressure, the unit cell parameter ratio of Os exhibits anomalies at approximately 150 gigapascals and 440 gigapascals. Dynamical mean-field theory calculations suggest that the former anomaly is a signature of the topological change of the Fermi surface for valence electrons. However, the anomaly at 440 gigapascals might be related to an electronic transition associated with pressure-induced interactions between core electrons. The ability to affect the core electrons under static high-pressure experimental conditions, even for incompressible metals such as Os, opens up opportunities to search for new states of matter under extreme compression.

[Analysis of the efficacy and prognostic factors of 1 637 esophageal cancer patients treated with intensity-modulated radiotherapy].

Objective: To summarize survival outcomes and prognostic factors in esophageal cancer (EC) patients treated with intensity-modulated radiotherapy (IMRT). Methods: A retrospective analysis was performed on the clinical and follow-up data of 1 637 patients with EC who were admitted to our hospital from January 2005 to December 2017 and met the inclusion criteria.The 5-year overall survival (OS), progression-free survival (PFS) and pattern of recurrence were analyzed. The Kaplan-Meier method was used to calculate survival rates, Log-rank test for univariate analysis and Cox method for multivariate analysis were used to detect survival difference. Results: 1-year, 3-year and 5-year OS and PFS of the entire group were 65.9% and 45.8%, 34.2% and 25.0%, 27.0% and 18.5%, respectively. Median OS and PFS were 19.4 months (95% CI=18.0-20.7 months) and 10.4 months (95% CI=9.3-11.3 months), respectively. Univariate analysis showed that the sex, KPS, tumor location, T stage, N stage, M stage, TNM stage, radiation dose and treatment modality were prognostic factors for 5-year OS and PFS of EC patients (P<0.05). Multivariate analysis indicated that the sex, KPS, TNM stage, radiation dose and treatment modality were independent prognostic factors for 5-year OS and PFS (P<0.05). Conclusions: EC patients treated with IMRT can obtain a promising survival. The sex, KPS, TNM stage, radiation dose and treatment modality are independent prognostic factors for prognosis.

[Application of Rotarex mechanical thrombectomy system in treating in-stent restenosis of lower extremity arteriosclerosis obliterans].

OBJECTIVE: To evaluate the role of Rotarex mechanical thrombectomy system in treating instent restenosis of peripheral artery disease (PAD). METHODS: The clinical data of 7 in-stent restenosis (ISR) cases of lower extremity PAD from June 2017 to Dec 2018 were retrospectively analyzed. There were 5 males and 2 females and the mean age was (70.0±7.6) years from 59.0 to 76.0 years. All the cases were treated by Rotarex mechanical thrombectomy system. In the 7 cases, time interval from the previous stent implantation to ischemia recurrence was 1.0 to 72.0 months, and the median time was 6.0 months. The period from ischemia recurrence to endovascular therapy was 3 days to 2 years, and the median time was 62 days. Rotarex mechanical debulking catheter and percutaneous transluminal angioplasty (PTA) were used in all the cases, and the stent was used only when it was necessary. Anticoagulation was used for 24 hours after procedures and then antiplatelet agents were used as usual. Doppler ultrasonography was taken during the followed-up. RESULTS: All the 7 cases were successful in technology, 3 of which were implanted with new stents for the fracture of the old ones. while for the other four cases, no new stent was implanted. The ankle-brachial index (ABI) increased from 0.31±0.08 to 0.86±0.08 after treatment (t=-12.84, P < 0.001). Thrombectomy was applied urgently in one case because of acute thrombosis in the stent, and the result was good. There was no other complications in hospital. All the patients were followed up for 5.0-22.0 months, and the median time was 14.0 months. No death and amputation occurred during the follow-up. One patient stopped antiplatelet agents because of gastrointestinal bleeding, which resulted in acute thrombosis. in-stent restenosis reappeared in 3 cases. CONCLUSION: Debulking using Rotarex catheter is safe and effective in treating in-stent restenosis of PAD, especially in reducing stents implantation, but is not good at dealing with old thrombus and proliferating intima, and can do nothing about fractured stents and hyperplasia of intima, so it needs to be combined with stents and drug coated balloons.

[Application of Rotarex mechanical thrombectomy system in acute lower limb ischemia].

OBJECTIVE: To evaluate the effectiveness and safety of Rotarex mechanical thrombectomy system in treating acute lower limb ischemia. METHODS: From December 2017 to December 2019, the clinical data of 23 acute lower limb ischemia cases treated with Rotarex mechanical thrombectomy system were retrospectively analyzed. There were 14 males and 9 females from 53- to 84-year-old patients and the mean age was (69.1±9.1) years. Duration of symptoms was 6 hours to 14 days (median time 7 days). In the study, 8 acute thromboembolism cases and 15 acute thrombosis cases were included (In which, there was one thromboangiitis obliterans case and two in-stent restenosis cases). In 5 cases, the lesions were located above the groin; in 16 cases, the lesions were located below the groin, and in the other 2 cases, the lesions were located both above and below the groin. All the cases were treated with Rotarex mechanical thrombectomy system. When residual stenosis was greater than 50%, percutaneous transluminal angioplasty (PTA) was used, and stent was used only when it was necessary. Heparin was used 24 h after the procedure, and after that, antiplatelet agents were used in acute thrombosis cases, and oral anti-coagulants were used in acute thromboembolism cases. Doppler ultrasonography was taken during the follow-up. RESULTS: In all the 23 cases, there were 22 successful cases and 1 unsuccessful case, the mean procedure time was (68.2±15.6) min. Percutaneous transluminal angioplasty was used in 18 cases, 7 of which were implanted stents (3 stents were implanted in iliac artery and 4 in superficial femoral artery). There were 3 procedure related complications. The first one was arterial wall injury which resulted in contrast medium extravazation, and in this case, we solved it with prolonged balloon inflation. The second one was distal embolism. We took out the thrombus with guiding catheter. The last one was acute occlusion in a stent, and thrombectomy was applied urgently, and the result was good. Mean hospital stay were (3.6±1.7) days. The ankle brachial index (ABI) increased from 0.25±0.10 to 0.85±0.16 after treatment (t=12.901, P < 0.001). All the patients were followed up for 4.0-28.0 months, and the median time was 12.0 months. One patient stopped antiplatelet agents, which resulted in acute thrombosis 2 months later. Another percutaneous mechanical thrombectomy and PTA were taken. In the failed case, the patient suffered amputation above the knee 3 months later and in another case, the patient died of heart failure 8 months after the procedure. Two target lesion restenosis occurred during the follow-up. Because the patients' symptom was not sever, no procedure was taken. CONCLUSION: Percutaneous mechanical thrombectomy using Rotarex catheter is safe and effective in treating acute lower limb ischemia. For one side, it can restore blood flow to the affected limbs quickly, and for the other, it has the characteristics of minimally invasive and good repeatability. So it should be considered that this me-thod can be widely used for acute lower limb ischemia.