No pulsed radio emission during a bursting phase of a Galactic magnetar.

Fast radio bursts (FRBs) are millisecond-duration radio transients of unknown physical origin observed at extragalactic distances1-3. It has long been speculated that magnetars are the engine powering repeating bursts from FRB sources4-13, but no convincing evidence has been collected so far14. Recently, the Galactic magnetar SRG 1935+2154 entered an active phase by emitting intense soft γ-ray bursts15. One FRB-like event with two peaks (FRB 200428) and a luminosity slightly lower than the faintest extragalactic FRBs was detected from the source, in association with a soft γ-ray/hard-X-ray flare18-21. Here we report an eight-hour targeted radio observational campaign comprising four sessions and assisted by multi-wavelength (optical and hard-X-ray) data. During the third session, 29 soft-γ-ray repeater (SGR) bursts were detected in γ-ray energies. Throughout the observing period, we detected no single dispersed pulsed emission coincident with the arrivals of SGR bursts, but unfortunately we were not observing when the FRB was detected. The non-detection places a fluence upper limit that is eight orders of magnitude lower than the fluence of FRB 200428. Our results suggest that FRB-SGR burst associations are rare. FRBs may be highly relativistic and geometrically beamed, or FRB-like events associated with SGR bursts may have narrow spectra and characteristic frequencies outside the observed band. It is also possible that the physical conditions required to achieve coherent radiation in SGR bursts are difficult to satisfy, and that only under extreme conditions could an FRB be associated with an SGR burst.

[Call attention to the role of chronic endometritis in recurrent pregnancy loss].

Chronic endometritis (CE) refers to the persistent inflammation of endometrium and is closely associated with infertility. Recurrent pregnancy loss (RPL), which has complex etiological factors, is two or more pregnancy loss of a couple before 20 weeks. However, CE is found in approximately 30% RPL patients, indicating that the endometrial immune microenvironment disorder caused by CE may play important role in RPL. Therefore, we should pay high attention and give CE screening to the RPL patients. Due to the inconsistent diagnostic criteria of CE, the relationship between RPL and CE remains controversial. Antibiotic is the primary treatment of CE. Using the higher CE diagnosis value can ensure effective treatment to RPL patient, and avoid the abuse of antibiotic. The effective treatment of CE can improve the pregnant outcomes of RPL patient.

[A case of heritable pulmonary arterial hypertension treated with long-term oral low-dose imatinib].

Heritable pulmonary arterial hypertension (HPAH) is a rare type of pulmonary arterial hypertension that often presents with progressive exertional dyspnea and for which there is no significant effective drug. A HPAH patient was admitted to our hospital more than three years ago, and the gene mutation was bone morphogenetic protein 2 (BMPR2). For the first 45 months, she was given oral imatinib 100 mg once daily, and her symptoms and hemodynamics improved significantly, with no apparent side effects. It is reported that, in combination with the characteristics of the case and related literatures, it provides clinicians with other feasible treatment options for HPAH.

[Hemodynamic changes with serial balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension].

Objective: To monitor hemodynamic changes during serial balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH). Methods: General clinical data of CTEPH patients diagnosed from October 2017 to January 2022 in Beijing Chaoyang Hospital were collected, and 83 patients who underwent at least 1 BPA treatment were included to analyze their 6 min walking distance, WHO functional class, N-terminal B-type natriuretic peptide precursor (NT-proBNP), troponin I (cTnI) and haemodynamic indices. Baseline and follow-up after the final BPA clinical data and hemodynamics, functional status and serial hemodynamics before each series of BPA were collected to evaluate the efficacy of BPA for CTEPH patients. Complications and managements were documented to confirm the safety of BPA for CTEPH patients. Results: Three hundred and forty BPA procedures were performed in 83 CTEPH patients. The median number of BPA procedures was 4.0 and a total of 2104 vessels were dilated. In general, mPAP [from 50.0(42.0-55.25) mmHg(1 mmHg=0.133 kPa) to 32.0(27.0-42.0) mmHg, P<0.001], PVR[from (806.6±323.2) dyn·s·cm-5 to 420.0(295.0-613.5) dyn·s·cm-5, P<0.001] were significantly improved compared with baseline, but not CO and CI. Functional parameters including WHO functional class Ⅰ/Ⅱ/Ⅲ/Ⅳ (from 0/35/34/14 to 43/32/7/1, P<0.001), 6MWD [from 364.5(300.0-429.5)m to 461.0(409.0-501.0)m, P<0.001], NT-proBNP [from 1 357.0(232.0-2 715.0) ng/L to 141.0(57.0-627.8) ng/L,P<0.001] were significantly improved compared with baseline. A cumulative (compared to baseline) and serial (compared to preceding BPA session) analysis of the sequential BPA session confirmed that a major hemodynamic improvement in PVR and mPAP occurred in the first 3 serial BPA treatments. There was a dose-response relationship: the more segments that were treated, the greater were the subsequent reduction in PVR and mPAP. There were 32.0 complications (9.4%) associated with BPA procedures, and the most common complication was pulmonary hemorrhage caused by catheter-related vascular injury. Conclusions: BPA is an effective and safe alternative for technically non-operable CTEPH patients. The hemodynamic benefits of BPA in CTEPH patients were cumulative and correlated with the total number of vessels successfully dilated.

[Preliminary study on automatic quantification and grading of leopard spots fundus based on deep learning technology].

Objective: To achieve automatic segmentation, quantification, and grading of different regions of leopard spots fundus (FT) using deep learning technology. The analysis includes exploring the correlation between novel quantitative indicators, leopard spot fundus grades, and various systemic and ocular parameters. Methods: This was a cross-sectional study. The data were sourced from the Beijing Eye Study, a population-based longitudinal study. In 2001, a group of individuals aged 40 and above were surveyed in five urban communities in Haidian District and three rural communities in Daxing District of Beijing. A follow-up was conducted in 2011. This study included individuals aged 50 and above who participated in the second 5-year follow-up in 2011, considering only the data from the right eye. Color fundus images centered on the macula of the right eye were input into the leopard spot segmentation model and macular detection network. Using the macular center as the origin, with inner circle diameters of 1 mm, 3 mm, and outer circle diameter of 6 mm, fine segmentation of the fundus was achieved. This allowed the calculation of the leopard spot density (FTD) and leopard spot grade for each region. Further analyses of the differences in ocular and systemic parameters among different regions' FTD and leopard spot grades were conducted. The participants were categorized into three refractive types based on equivalent spherical power (SE): myopia (SE<-0.25 D), emmetropia (-0.25 D≤SE≤0.25 D), and hyperopia (SE>0.25 D). Based on axial length, the participants were divided into groups with axial length<24 mm, 24-26 mm, and>26 mm for the analysis of different types of FTD. Statistical analyses were performed using one-way analysis of variance, Kruskal-Wallis test, Bonferroni test, and Spearman correlation analysis. Results: The study included 3 369 participants (3 369 eyes) with an average age of (63.9±10.6) years; among them, 1 886 were female (56.0%) and 1, 483 were male (64.0%). The overall FTD for all eyes was 0.060 (0.016, 0.163); inner circle FTD was 0.000 (0.000, 0.025); middle circle FTD was 0.030 (0.000, 0.130); outer circle FTD was 0.055 (0.009, 0.171). The results of the univariate analysis indicated that FTD in various regions was correlated with axial length (overall: r=0.38, P<0.001; inner circle: r=0.31, P<0.001; middle circle: r=0.36, P<0.001; outer circle: r=0.39, P<0.001), subfoveal choroidal thickness (SFCT) (overall: r=-0.69, P<0.001; inner circle: r=-0.57, P<0.001; middle circle: r=-0.68, P<0.001; outer circle: r=-0.72, P<0.001), age (overall: r=0.34, P<0.001; inner circle: r=0.30, P<0.001; middle circle: r=0.31, P<0.001; outer circle: r=0.35, P<0.001), gender (overall: r=-0.11, P<0.001; inner circle: r=-0.04, P<0.001; middle circle: r=-0.07, P<0.001; outer circle: r=-0.11, P<0.001), SE (overall: r=-0.20; P<0.001; inner circle: r=-0.19, P<0.001; middle circle: r=-0.20, P<0.001; outer circle: r=-0.20, P<0.001), uncorrected visual acuity (overall: r=-0.18, P<0.001; inner circle: r=-0.26, P<0.001; middle circle: r=-0.24, P<0.001; outer circle: r=-0.22, P<0.001), and body mass index (BMI) (overall: r=-0.11, P<0.001; inner circle: r=-0.13, P<0.001; middle circle: r=-0.14, P<0.001; outer circle: r=-0.13, P<0.001). Further multivariate analysis results indicated that different region FTD was correlated with axial length (overall: ß=0.020, P<0.001; inner circle: ß=-0.022, P<0.001; middle circle: ß=0.027, P<0.001; outer circle: ß=0.022, P<0.001), SFCT (overall: ß=-0.001, P<0.001; inner circle: ß=-0.001, P<0.001; middle circle: ß=-0.001, P<0.001; outer circle: ß=-0.001, P<0.001), and age (overall: ß=0.002, P<0.001; inner circle: ß=0.001, P<0.001; middle circle: ß=0.002, P<0.001; outer circle: ß=0.002, P<0.001). The distribution of overall (H=56.76, P<0.001), inner circle (H=72.22, P<0.001), middle circle (H=75.83, P<0.001), and outer circle (H=70.34, P<0.001) FTD differed significantly among different refractive types. The distribution of overall (H=373.15, P<0.001), inner circle (H=367.67, P<0.001), middle circle (H=389.14, P<0.001), and outer circle (H=386.89, P<0.001) FTD differed significantly among different axial length groups. Furthermore, comparing various levels of FTD with systemic and ocular parameters, significant differences were found in axial length (F=142.85, P<0.001) and SFCT (F=530.46, P<0.001). Conclusions: The use of deep learning technology enables automatic segmentation and quantification of different regions of theFT, as well as preliminary grading. Different region FTD is significantly correlated with axial length, SFCT, and age. Individuals with older age, myopia, and longer axial length tend to have higher FTD and more advanced FT grades.

Quantifying sustained pain worsening in knee osteoarthritis.

OBJECTIVE: Recent work suggests that many persons with knee osteoarthritis (OA) experience stable symptoms over time. Whether patients experience periods of symptom exacerbation or flare which interrupt this stable course, and how long such periods last, has received little study. Our objective is to describe the frequency and duration of episodes of pain worsening in persons with knee OA. METHODS: We selected participants from the Osteoarthritis Initiative with radiographic, symptomatic knee OA. We defined a clinically relevant increase in knee pain as an increase in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain of ≥9 points. We defined sustained worsening as maintaining at least 80% of the initial increase. We used Poisson regression to estimate the incidence rate (IR) of episodes of pain worsening. RESULTS: 1093 participants were included in the analysis. Eighty-eight percent had ≥1 increase in WOMAC pain ≥9 points (IR: 26.3 per 100 person years (95% CI: 25.2, 27.4)). Forty-eight percent had ≥1 episode of sustained worsening (IR: 9.7 per 100 person-years (95% CI: 8.9, 10.5)). Elevated pain was maintained an average of 2.4 years after the initial increase. CONCLUSION: Most participants with knee OA reported at least one clinically relevant increase in WOMAC pain, but fewer than half experienced an episode of sustained pain worsening. These individual-level data portray a more nuanced and fluctuating course of OA pain than suggested by trajectory studies. These data could be useful in shared decision-making regarding prognosis and treatment choices in persons affected by symptomatic knee OA.

[Strengthening the construction of standardized system to enhance the standard diagnosis, treatment and comprehensive management of pulmonary hypertension in China].

In recent years, there has been rapid progress in the field of pulmonary hypertension (PH). With the deeper understanding of the pathogenesis of PH, the increase of evidence-based medical evidence, the continuous updating of PH clinical classification, the hemodynamic diagnostic boundaries, and the emergence of new targeted drugs and interventions, the guidelines are constantly being updated. It brings new challenges to the standard diagnosis, treatment and comprehensive management of PH in China. Compared with the world, there are still many problems in the field of PH in China. The heterogeneity of PH causes the complexity of the disease and the difficulty of clinical management, and the early identification and diagnosis of pH face great challenges. Individualized and precise treatment needs to be further optimized, and standardized diagnosis and treatment strategies need to be popularized and promoted. In recent years, rapid progress has been made in the field of PH, including its pathogenesis, diagnostic thresholds, classification and comprehensive treatment methods, prompting an update of the guidelines, which brings a new level of standardized diagnosis and comprehensive management of PH in China. This guideline brings new challenges to the standardized diagnosis and treatment and comprehensive management of PH in China. Here, we discussed in depth the current situation of diagnosis and treatment in the field of PH, as well as the development of a standardized system for PH in China.

[Research progress of thrombolytic therapy for high risk and intermediate-high risk pulmonary thromboembolism].

Acute pulmonary thromboembolism (PTE) is a highly fatal disease. Fibrinolytic therapy can rapidly improve pulmonary hemodynamics and is an important life-saving treatment. How to screen patients who may benefit from thrombolytic therapy and how to reduce the complications of major bleeding are still the focus of PTE treatment. In addition, as our understanding of post-PE syndrome (PPES) has improved, much attention has been paid to whether thrombolytic therapy has any benefit in preventing PPES. This article reviewed the research progress of early risk stratification and prognosis assessment, early major bleeding risk assessment, thrombolytic drug dose reduction, interventional thrombolysis and the long-term prognosis of PTE thrombolysis in recent years.

[Screening for asymptomatic atrial fibrillation in elder community populations in Dalian: a single center study].

Objective: We aimed to determine the epidemiological characteristics of asymptomatic AF in elder community population (≥65 years old) to analyze the detection rate of different screening methods. Methods: The study was a prospective cohort study. The elder (≥65 years old) residents who voluntarily participated in free physical examination in Dalian community were selected. The participants were randomly divided into screening group (including intensive screening group and single screening group) and control group. The control group received interrogation, medical history collection and routine 12-lead electrocardiogram (ECG) examination. Screening group received an additional single-lead ambulatory ECG equipment worn for 5-7 days. Intensive screening group received two equal-length wearings in 2020 and 2021 respectively, while one screening group only wore once in 2020. Results: Finally 3 340 residents ((70.7±5.0) years old) which consisted of 1 488 males (44.55%) were enrolled. There were 1 945 residents in screening group, including 859 in intensive screening group and 1 086 in one-time screening group. The control group included 1 395 people. Detection rate of asymptomatic AF was significantly higher in screening group than control group (79(4.06%) vs. 24(1.72%), P<0.001). Higher detection rate was found in screening group than control group in AF risk factors (1 or 2-3) subgroups and CHA2DS2-VASc score (2-3 or≥4) subgroups (P<0.05). Additionally, no difference was found between intensive screening group and single screening group (42(4.89%) vs. 37(3.41%), P=0.100). Intensive screening increased detection rate (7(6.93%) vs. 1(0.58%), P=0.009) only in residents those with low thrombosis risk (CHA2DS2-VaSc<2). Conclusions: Screening in elderly (≥65 years old) can significantly improve the detection rate of asymptomatic AF by wearing single lead dynamic ECG device. The rate increased significantly with the increase of risk factors associated with AF by single screening. In addition, repeat screening of the same method may only improve detection rates in the group with low risk thrombotic scores and non-combination of AF risk factors.Screening methods that are appropriate for different populations may require further exploration.

Effectiveness of denosumab for fracture prevention in real-world postmenopausal women with osteoporosis: a retrospective cohort study.

To determine denosumab's effectiveness for fracture prevention among postmenopausal women with osteoporosis in East Asia, the risk of fracture was compared between patients continuing denosumab therapy versus patients discontinuing denosumab after one dose. The real-world effectiveness was observed to be consistent with the efficacy demonstrated in the phase III trial. INTRODUCTION: After therapeutic efficacy is demonstrated for subjects in global clinical trials, real-world evidence may provide complementary knowledge of therapeutic effectiveness in a heterogeneous mix of patients seen in clinical practice. This retrospective cohort study was conducted to compare the fracture risk in real-world clinical care received in Taiwan and Hong Kong between a treatment cohort (patients receiving denosumab 60 mg subcutaneously every 6 months) versus an off-treatment cohort (patients discontinuing after 1 dose of denosumab, which has no known clinical benefit) among real-world postmenopausal women. METHODS: This study included 38,906 and 2,835 postmenopausal women receiving denosumab in Taiwan and Hong Kong, respectively. The primary endpoint was hip fracture, and secondary endpoints were clinical vertebral and nonvertebral fractures. Propensity-score-matched analysis, adjusting for known covariates, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The robustness of findings was evaluated with a series of sensitivity and quantitative bias analyses. RESULTS: In this study, 554 hip fractures were included in the primary Taiwan population analysis. The crude incidence rate was 0.9 per 100 person-years in the treatment cohort (n = 25,059) and 1.7 per 100 person-years in the off-treatment cohort (n = 13,847). After adjusting for prognostic differences between cohorts, denosumab reduced the risk of hip fractures by 38% (HR = 0.62, CI:0.52-0.75). Risk reductions of similar magnitude were observed for the secondary endpoints and for the analysis of the smaller Hong Kong population. CONCLUSION: The effectiveness of denosumab for fracture reduction among real-world postmenopausal women with osteoporosis was consistent with the efficacy demonstrated in a global clinical trial. REGISTRATION: EnCePP registration number: EUPAS26372; registration date: 12/11/2018.

[Berberine alleviates programmed necrosis of metabolic-associated fatty liver disease via activating Nrf2 pathway in mice].

Objective: To investigate the effect of berberine on programmed necrosis of hepatocytes induced by metabolic-associated fatty liver disease (MAFLD) in mice and its related molecular mechanism. Methods: Twenty male C57BL/6N mice were randomly divided into four groups (n=5 in each group): control group (S), fatty liver group (H), berberine group(B), nuclear factor erythroid 2-related factor 2 inhibitor group (Nrf2), and all-trans-retinoic acid (ATRA) group (A). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), triglycerides (TG), total cholesterol (TC), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) concentrations were detected at the end of week 12 to calculate fatty liver index (liver mass/body mass ratio). Liver tissue was stained with HE, Masson and Oil Red O, and SAF score was used to evaluate the degree of liver injury. The expression levels of hepatic programmed necrosis-related proteins, namely receptor-interacting protein kinase 3 (RIPK3), phosphorylated mixed series protease-like domain (p-MLKL) and Nrf2 were detected by Western blot method. One-way ANOVA was used for intragroup comparisons and LSD-t tests were used for intergroup comparisons. Results: Compared with S group, H group serum ALT, AST, LDH, TG, TC, TNF-α, IL-1ß levels and fatty liver index were significantly increased. The liver tissue was filled with vacuolar-like changes and inflammatory cell infiltration. Numerous red lipid droplets were observed with oil red O staining. Collagen fiber hyperplasia was evident with Masson staining. SAF scores (6.60 ± 0.55 and 0.80 ± 0.45) were significantly increased. The expressions of RIPK3 and p-MLKL were up-regulated. Nrf2 level was relatively increased, and the differences were statistically significant (P < 0.05). Compared with H group, berberine intervention group liver biochemical indexes, lipid levels, pro-inflammatory mediator expression, fatty liver index, and SAF score were significantly reduced, and the expression of RIPK3 and p-MLKL were down-regulated, while Nrf2 levels were further increased, and the differences were statistically significant (P<0.05). Compared with B group, treatment with Nrf2 inhibitor had antagonized the protective effect of berberine on fatty liver. Serum ALT, AST, LDH, TG, TC and TNF-α, IL-1ß levels, fatty liver index, and SAF scores were significantly increased and the expressions of RIPK3 and p-MLKL were relatively increased, and the differences were statistically significant (P < 0.05). Conclusion: Berberine can significantly improve the metabolic-associated fatty liver disease injury in mice, and its mechanism is related to activation of Nrf2 and inhibition of programmed necrosis of hepatocytes.

[Clinical characteristics and prognostic factors of 1 166 patients with uveal melanoma].

Objective: To analyze the clinical characteristics and survival of Chinese uveal melanoma (UM) patients. Methods: It was a retrospective case series study. Clinical data and demography characteristics of 1 166 UM patients who were diagnosed in Beijing Tongren Hospital from January 2004 to January 2020 were collected. The disease was followed up after informed consent was obtained. Kaplan-Meier plots were used to visualize survival outcomes, and the different risk groups were compared using the Log-rank test. The multivariate Cox proportional hazards model was used to select independent prognostic risk factors. Results: A total of 1 166 individuals (598 men, 568 women) were included in this study. The average age was (47.6±12.2) years. Median follow-up time was 38 months. Treatment included episcleral brachytherapy in 881 (75.6%) patients, local tumor resection in 38 (3.2%) patients, laser therapy in 115 (9.9%) patients and primary enucleation in 119 (10.2%) patients. In 120 patients out of the 881 patients with primary brachytherapy, enucleation was performed due to an increasing tumor size or uncontrolled neovascular glaucoma. The Kaplan-Meier survival analysis showed the 5-and 10-year metastasis rates were 18.5% and 26.8%, and the melanoma-related mortality rates were 13.6% and 22.2%, respectively. The Log-rank test showed that patient age (χ²=5.01) and gender (χ²=7.19), as well as tumor grade (χ²=49.11), shape (χ²=34.73), location (χ²=18.60), pathological type (χ²=8.07), presence of subretinal fluid (χ²=15.71) and ciliary body involvement (χ²=19.72) were factors influencing patient prognoses (all P<0.05). In the multivariate Cox analysis, the T2, T3, T4 tumors (compared with the T1 tumor, HR=4.41, 6.82, 10.49), subretinal fluid (HR=1.98), ciliary body involvement (HR=1.79), being male (HR=1.53) and advanced age (greater than 53 years old) (HR=1.83) were independent risk factors for poor prognoses (all P<0.05). Conclusions: UM occurs at a significantly earlier age and non-pigmented tumors represent smaller proportion in Chinese patients. Higher T-stage, presence of subretinal fluid, ciliary body involvement, advanced age, and being male are independent risk factors for poor outcomes.

[Short-term efficacy and perioperative safety of catheter-based intervention for pulmonary vein stenosis caused by fibrosing mediastinitis].

Objective: To evaluate the short-term efficacy and perioperative safety of catheter-based intervention in patients with pulmonary vein stenosis caused by fibrosing mediastinitis (FM). Methods: It was a case series study. Consecutive patients with pulmonary vein stenosis caused by FM, who underwent percutaneous pulmonary vein angioplasty in Gansu Provincial Hospital from January 2018 to June 2020, were retrospective enrolled. The baseline characteristics, comorbidities, exercise capacity and hemodynamic data before and after treatment were compared, and the procedural related complications were evaluated. Results: A total of 30 patients ((64.3±7.1) years, 15 males) were included. Sixty-three pulmonary vein stenosis were treated by 32 percutaneous pulmonary vein angioplasty procedures. Forty-four stents were implanted in 41 pulmonary veins after balloon angioplasty, and the diameter of implanted stents was (8.3±1.2)mm. Balloon angioplasty was performed on 22 pulmonary vein stenosis, the mean balloon diameter was (4.2±2.1)mm. The pulmonary vein diameter increased from (2.6±1.3) to (6.6±2.6) mm (P<0.001) and the pressure gradient across the pulmonary vein stenotic segment reduced from 19 (12, 29) to 2 (0, 4) mmHg (1 mmHg=0.133 kPa) (P<0.001) immediately post procedure. The pulmonary vein flow grade was significantly improved compared with baseline (P<0.001). The most common operation related complications were lung injury (44.0% (11/25)) and hemoptysis (18.8% (6/32)), which did not need special treatment. During the 2.0 (1.3, 3.2) months follow-up, the WHO functional class was significantly improved (P<0.05), the 6-minute walking distance increased from (254.8±114.5) m to (342.8±72.4)m (P<0.05), the mean pulmonary arterial pressure decreased from (40.9±8.3) mmHg to (35.4±7.7) mmHg (P<0.01), 17 out of 19 patients with refractory pleural effusion experienced total remission during the follow-up period (P<0.001). CT pulmonary venography was repeated in 17 patients. The incidence of in-stent restenosis of pulmonary vein was 24.0% (6/25). Conclusions: Percutaneous pulmonary vein angioplasty is effective for the treatment of pulmonary vein stenosis caused by fibrosing mediastinitis. However, it's not so safe, procedural related complication should be paid attention to and the rate of in-stent restenosis is relative high during the short-term follow-up.

[Establishment of human colon cancer transplantation tumor model in normal immune mice].

Objective: Establishment of a new model of human primary colon cancer transplantation tumor in normal immune mice and to provide a reliable experimental animal model for studying the pathogenesis of colon cancer under normal immunity. Methods: Human colon cancer cells come from colon cancer patients who underwent surgery in the Affiliated Hospital of Jining Medical College in 2017. The mice in the cell control group were inoculated with phosphate buffered solution (PBS) containing colon cancer cells, the microcarrier control group was inoculated with PBS containing microcarrier 6, and the cell-microcarrier complex group was inoculated with the PBS containing colon cancer cell-microcarrier complex. The cells of each group were inoculated under the skin of the right axilla of mice by subcutaneous injection, and the time, size, tumor formation rate and pathological changes under microscope were recorded. The transplanted tumor tissue was immunohistochemically stained with the EnVisiion two-step method, and the tumor formation rate of the transplanted tumor was judged according to the proportion of positive cells in the visual field. The polymerase chain reaction (PCR) method was used to detect the expression of human-specific Alu sequence in mice tumor tissue. Results: After inoculation with tumor cells, the mice in the cell control group and the microcarrier control group did not die and did not form tumors; the mice in the cell-microcarrier complex group had palpable subcutaneous tumors in the right axillary subcutaneously on the 5th to 7th days after inoculation, and tumor formation rate is 67% (10/15), and the tumor volume can reach about 500 mm(3) 2 to 3 weeks after vaccination. The immunohistochemistry results showed that CK20, CDX-2 and carcinoembryonic antigen were all positively expressed. The PCR results showed that the expression of human-specific Alu sequence can be detected in the transplanted tumor tissue of tumor-bearing mice. Conclusion: Human primary colon cancer cells used microcarrier 6 as a carrier to form tumors in normal immunized mice, and successfully established a new model of human colon cancer transplantation tumor in normal immune mice.

[Effect of corticotomy techniques accelerating orthodontic tooth movement on root resorption].

In recent years, developing new methods to accelerate orthodontic tooth movement (OTM) has attracted extensive attention in the field of orthodontic clinical and scientific research. It reduces orthodontic treatment time and risks. Over the past, various approaches have been done to accelerate orthodontic tooth movement. Several forms of corticotomy techniques have been effective in inducing rapid tooth movement. These techniques activate regional acceleratory phenomenon and create a favorable microenvironment for accelerating tooth movement. Root resorption is one of most common side effects of orthodontic treatment. It affects the long-term viability and health of teeth. However, the effect of corticotomy techniques accelerating orthodontic tooth movement on root resorption still remains unclear. Accelerating tooth movement may have two-side effects on root resorption. Through shortening the treatment period and removing the hyalinized tissues, the acceleration of orthodontic tooth movement could reduce root resorption. The increase of root resorption might be due to the local inflammation and function of cementoclasts/odontoclasts. In this paper, we reviewed the effects of different corticotomy techniques accelerating orthodontic tooth movement on root resorption. Corticotomy techniques deal with mucoperio-steal flaps and bone tissues differently and develop towards minimally invasive. Previous studies on root resorption use two-dimensional images, including apical films and panoramic tomography, to evaluate the degree of root resorption. In recent years, researches measure the volume of root resorption accurately using cone-beam computed tomography (CBCT) and micro-CT. Most studies suggest that the root resorption during acceleration of orthodontic tooth movement through corticotomy techniques is not statistically different from that of traditional orthodontic treatment. Some studies using micro-CT have shown that the root resorption in the groups of corticotomy techniques increases compared with the control group without surgery. Because of the short duration of these studies, the clinical significance is controversial on the overall impact of corticotomy techniques on orthodontic treatment. Accelerating orthodontic tooth movement is still at its emerging phase and need further research in the form of clinical trials to illustrate the effect of corticotomy techniques accelerating orthodontic tooth movement on root resorption.

[Clinical study of percutaneous vertebroplasty combined with (125)I seeds implantation in the treatment of patients with thoracic metastatic tumor complicated with posterior vertebral defect].

Objective: To analyze the safety and efficacy of percutaneous vertebroplasty combined with interstitial implantation (125)I of seeds (PVPI) in the treatment of thoracic vertebroplasty with posterior vertebra defect. Methods: A retrospective analysis of the clinical data of 64 patients with thoracic spine metastases admitted to Yunnan Cancer Hospital from November 2017 to May 2019 was conducted, including 32 patients with posterior vertebra defect (experimental group) and 32 cases without (control group). Forty-two vertebral bodies of 32 patients in the experimental group were treated with improved PVPI surgery, which performed with the secondary sealing method and inclined puncture needle injection bone cement rotary filling technology, to reduce leakage. The 54 vertebral bodies of 32 patients in control group underwent PVPI. The two groups of patients were followed up on the second day, one month, three months and six months after the operation, and the short-term efficacy, long-term efficacy and safety indicators of the two groups were compared. Results: All 64 patients successfully completed the surgical treatment. The visual analogue scores and Karnofsky scores of the experimental group and the control group were improved to varying degrees on the second day, 1 month, 3 months and 6 months after the operation. There was no statistically significant difference between the two groups (P>0.05). The amount of bone cement in the experimental group and control group was (2.36±0.20) ml and (2.39±0.17) ml, and the difference was not statistically significant (P=0.482). The amount of (125)I seed implantation was (30.63±0.91) and (32.56±0.68), respectively, the difference was not statistically significant (P=0.925). The partial response rates of the study group and the control group were 81.3% and 87.5%, the stable disease rates were 12.5% and 9.4%, the differences were not statistically significant (P>0.05). The median overall survival (mOS) of the study group was 13 months, and the median progression-free survival (mPFS) was 8 months. The mOS of the control group was 14 months, and the mPFS was 8 months. The differences were not statistically significant (P>0.05). In the experimental group, 6 (14.3%) vertebral bodies had cement leakage, of which 2 (4.8%) were cement leakage at posterior vertebra, 4 (9.5%) were paravertebral cement leakage. Seven (13.0%) paravertebral cement leakage occurred in the control group. There was no significant difference in bone cement leakage between the two groups (P=0.097). Bone cement leakage in both groups did not cause serious complications such as spinal cord injury and paraplegia. Conclusion: The application of PVPI in the treatment of thoracic metastatic tumor patients with posterior vertebra defect can acquire better clinical efficacy and safety through conduction of the improved intraoperative technology and paying more attention to the control of bone cement distribution and other issues.

[The role of pulmonary arterial pressure in chronic obstructive pulmonary disease phenotypes based on cluster analysis and its prognostic value].

Objective: To explore the role of pulmonary arterial pressure in chronic obstructive pulmonary disease (COPD) phenotypes based on cluster analysis and its prognostic value. Methods: Three hundred and nineteen patients admitted to Beijing Chaoyang Hospital and Xuanwu Hospital from April 2013 to April 2016 were recruited in the study. All the patients were older than 40 years old and in stable COPD. One-year follow-up was performed and the endpoint was acute exacerbation of COPD or all-cause mortality. Age, body mass index (BMI), smoking index, history of exacerbation, modified British medical research council (mMRC), forced expiratory volume in first second (FEV(1)), pulmonary arterial pressure and right ventricular transverse diameter measured by echocardiography were selected as cluster indicators to classify patients, survival analysis was performed. Results: Eight cluster indexes were converted into four independent principal components by principal component analysis (PCA), with a cumulative contribution rate of 70.1%. The extracted principal components were used for cluster analysis. Patients were divided into four categories, each contained different GOLD grades and had statistically significant differences in age, symptoms, degree of pulmonary function impairment and pulmonary arterial pressure (all P<0.001). The four categories were: class 1: young, pulmonary function damage was medium, lower pulmonary arterial pressure, good prognosis; class 2: elderly, pulmonary function damage was mild, higher pulmonary arterial pressure, poor prognosis; class 3: young, pulmonary function damage was serious, normal pulmonary arterial pressure, the best prognosis; class 4: elderly, pulmonary function damage was medium, pulmonary arterial pressure increased significantly, the worst prognosis. Conclusion: Cluster analysis based on pulmonary artery pressure can be used to identify COPD patients with different risk of acute exacerbation or death, suggesting that pulmonary hypertension as a COPD phenotype plays a role in prognostic assessment.

[Effect of HIF-1α and BRD4 on autophagy level of breast cancer cell in hypoxic microenvironment].

Objective: To investigate the expressions of HIF-1α, BRD4, Beclin1, LC3B and p62 in breast cancer tissues and their clinicopathological significance, and to study alterations of their expression in breast cancer cells under hypoxic microenvironment. Methods: Immunohistochemistry was used to detect HIF-1α, BRD4, Beclin1, LC3B and p62 protein expressions in 125 breast cancer tissues and 50 para-cancer normal breast tissues, and their correlation with clinicopathologic characteristics were analyzed. The expression of these proteins were also measured after 24 hours of hypoxia stimulation was detected in different breast cancer cell lines and normal breast epithelial cells. Results: The expression of HIF-1α, BRD4, Beclin1 and LC3B proteins in breast cancer tissues were significantly higher than in para-cancer normal breast tissues (P<0.05). There was a positive association between histologic grade, the expression of HIF-1α, BRD4, Beclin1 and LC3B (P<0.05). High expressions of HIF-1a and Beclin1 were often correlated with lymph node metastasis and lymphatic invasion (P<0.05). Increased HIF-1α, BRD4, Beclin1 and LC3B expression was associated with ER or PR negativity, but only HIF-1α was associated with HER2 positivity (P<0.05). HIF-1α, BRD4, Beclin1, and LC3B were positively correlated with each other in breast cancer tissues (P<0.01). After 24 hours of hypoxic stimulation, the expression of HIF-1α, BRD4, Beclin1 and LC3B was up-regulated in breast cancer cells. Conclusions: Hypoxia induces autophagy in breast cancer tissues. HIF-1α is positively correlated with BRD4, suggesting that BRD4 is involved in the regulation of autophagy by hypoxic microenvironment in breast cancer. High expression of HIF-1α, BRD4 and autophagy may play an important role in the development of breast cancer.

[A retrospective study of balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension].

Objective: To analyze the efficacy and safety of Balloon Pulmonary Angioplasty (BPA) in patients with Chronic Thromboembolic Pulmonary Hypertension (CTEPH). Methods: A total of 38 CTEPH patients received at least one BPA treatment between February 2017 and April 2019 were enrolled. World Health Organization functional class(WHO-FC), 6-minute walking distance(6WMD), mean pulmonary artery pressure (mPAP), pulmonary vascular resistance(PVR), N-terminal pro brain natriuretic peptide(NT-proBNP) and echocardiographic indicators were collected at baseline and before each BPA procedure. Results: 38 patients received 95 times of BPA [ 2 (1, 4) times per person] totally. MPAP was 50 (43, 56) mmHg(1 mmHg=0.133 kPa) before BPA and 41(32, 50) mmHg after at least one BPA procedure, P<0.001. MPAP decreased from 50(42, 55) to 34(28, 49) mmHg (P=0.003) in 17 cases after 3-5 BPA procedures. In 15 cases, PVR decreased from 852(583, 1 140)dyn·s·cm-5 to 496(406, 802)dyn·s·cm-5, P=0.009. Besides, there were 13 patients with WHO Function Class Ⅰ/Ⅱ before BPA, 25 patients with Ⅲ/Ⅳ class before BPA, 29 patients with Ⅰ/Ⅱ class after BPA treatment, and 9 patients with Ⅲ/Ⅳ after BPA treatment, P<0.001. 6 WMD before and after BPA increased from 360(290, 442)m to 449(376, 505)m, P=0.015. The Meyer score of lung perfusion scanning got improved, from 0.54(0.53, 0.58) to 0.50(0.44, 0.58), P<0.001. Among all registered patients, 21 of whom NT-proBNP decreased from 1 285(606, 2 794) to 472(148, 745), P=0.014. The inner diameter of the right ventricular decreased from 54(41, 54)mm before surgery to 42(34, 49)mm after surgery, P<0.001. 6(6.3%, 6/95) complications occurred in 95 times of BPA. Conclusion: For inoperable patients with CTEPH, BPA can significantly improve disease severity, 6 MWD, heart function, decrease mPAP, PVR and improve lung perfusion, which is a safe and effective therapy.

Metabolic disorder induces fatty liver in Japanese seabass, Lateolabrax japonicas fed a full plant protein diet and regulated by cAMP-JNK/NF-kB-caspase signal pathway.

A 10-week growth trial was conducted to investigate the effects of replacing dietary fishmeal with plant proteins on nutrition metabolism, immunity, inflammation and apoptosis responses in liver tissues of Japanese seabass, Lateolabrax japonicas (initial body weight = 10.42 ±â€¯0.01 g). Two isonitrogenous and isoenergetic diets were formulated. A basal diet containing 54% fishmeal (FM), whereas another diet was prepared by totally replacing FM with a plant protein blend (PP) composed with soybean protein concentrate and cottonseed protein concentrate. Although essential amino acids, fatty acids, and available phosphorus had been balanced according to the FM diet profile, the significantly lower growth performance, metabolic disorder, and fatty liver symptom were observed in the PP group. Compared with the FM group, fish in the PP group showed significantly lower plasma free EAA level and PPV. Glucose metabolism disorder was expressed as the uncontrollable fasting glycolysis and pyruvate aerobic oxidation at postprandial 24 h with significantly up-regulated GK, PK and PDH genes expression, which potentially over-produced acetyl-CoA as the substrate for protein and lipid synthesis. Significantly reduced plasma GLU, but increased GC level, along with very significantly reduced liver GLY storage could be observed in the PP group. Plasma TG and hepatic NEFA contents were significantly decreased, but the hepatic TC content was very significantly increased in the PP group, in addition, hepatocyte vacuolation appeared. The significantly up-regulated cholesterol synthesis gene (HMGCR) expression but down-regulated bile acid synthesis gene (CYP7A1) expression could be the main reason for the fatty liver induced by cholesterol accumulation. The reduced plasma IgM content accompanied by the up-regulated mRNA levels of pro-inflammatory cytokines (TNFα and IL1ß) and activated apoptosis signals of liver tissues were found in the PP group. The hyperthyroidism (higher plasma T3 and T4) and the accelerated energy metabolism rate decreased the growth performance in the PP group. The activated p65NF-kB may promote the hepatocytes apoptosis via the extrinsic pathway (caspase8/caspase3). Simultaneously, a "self-saving" response could be observed that activated cAMP promoted the lipolysis/ß-oxidation process and up-regulated gene expression of anti-inflammatory cytokine IL10 via promoting CREB expression, further inhibited the over-phosphorylation of JNK protein, which might impede the intrinsic apoptosis pathway (caspase9/caspase3). In conclusion, the nutrient and energy metabolic disorder induced fatty liver related to the cholesterol accumulation in Japanese seabass fed full PP diet, which was under the regulation by cAMP-JNK/NF-kB-caspase signaling pathway. The hemostasis phosphorylation of JNK protein protected the liver tissues from more serious damage.