Molecular rectification induced by magnetization alignment in organic-ferromagnetic devices.

Spin-dependent transport in ferromagnet/organic-ferromagnet/ferromagnet junctions is investigated theoretically under different alignment of magnetization orientations. The results demonstrate a significant current rectification at low bias voltages, and the rectifying direction relies on the relative magnetization orientation in each component. The orbital analysis demonstrates two underlying mechanisms for the rectification, the slight structural asymmetry of the molecule from spin radicals and distinct spin match between conducting electrons and the magnetic molecule upon the reversal of bias. The latter is responsible for the strong low-bias rectification and relies on the magnetization alignment. The effects of parameter strength, temperature and size on the rectification are discussed. This work explores a new route to achieve high-performance molecular rectifiers operating at low bias with controlled rectifying direction.

Surgical treatment of nasopharyngeal cancer - a consensus recommendation from two Chinese associations.

BACKGROUND: Surgical treatment is playing an increasingly important role in the management of nasopharyngeal carcinoma (NPC). This consensus focuses on the indications for optimal surgery, and surgical methods in the whole process of treatment for NPC to provide a useful reference to assist these difficult clinical decisions. METHODOLOGY: A thorough review of available literature on NPC and surgery was conducted by the Association for the prevention and treatment of nasopharyngeal carcinoma in China, international exchange and promotion Association for medicine and healthcare, and the Committee on nasopharyngeal cancer of Guangdong provincial anticancer association. A set of questions and a preliminary draft guideline was circulated to a panel of 1096 experienced specialists on this disease for voting on controversial areas and comments. A refined second proposal, based on a summary of the initial voting and different opinions expressed, was recirculated to the experts in two authoritative medical science and technology academic groups in the prevention and treatment of NPC in China for review and reconsideration. RESULTS: The initial round of questions showed variations in clinical practice even among similar specialists, reflecting the lack of high-quality supporting data and resulting difficulties in formulating clinical decisions. Through exchange of comments and iterative revisions, recommendations with high-to-moderate agreement were formulated on general treatment strategies and details of surgery, including indications and surgical approaches. CONCLUSION: By standardizing the surgical indications and practice, we hope not only to improve the surgical outcomes, but also to highlight the key directions of future clinical research in the surgical management of NPC.

[New insights into the role of macrophages in tumor immunotherapy].

Macrophages are the main components of the innate immunity system, derived mainly from blood monocytes, and help the host to defend itself against many pathogens and cancers. Most established tumors can educate macrophages into tumor-associated macrophages (TAMs), which contribute to tumor growth, invasion and metastasis, as well as resistance to chemotherapeutic agents and immune checkpoint inhibitors. However, when appropriately activated, macrophages can also exert anti-tumor effects through enhanced phagocytosis and cytotoxicity against tumor cells. In addition, TAMs are associated with poor prognosis and drug resistance, including immunotherapies, suggesting that macrophages are attractive targets as part of combination therapy in cancer treatment. Herein, we review the recent findings on the role of macrophages in tumor development, metastasis and immunotherapy. We focus mainly on macrophage-centered therapy, including strategies to reduce and reshape TAMs, to represent potential targets for tumor immunotherapy.

Identification of ovarian endometriotic cysts in cystic lesions of the ovary by amide proton transfer-weighted imaging and R2∗ mapping.

AIM: To investigate the value of amide proton transfer weighted (APTw) imaging and R2∗ mapping of cystic fluid in differentiating ovarian endometriotic cysts (OE) from other ovarian cystic (OOC) lesions. MATERIALS AND METHODS: A total of 42 patients who underwent 3 T pelvic magnetic resonance imaging (MRI) were enrolled. Nineteen lesions were OE and 27 lesions were OOC. The APTw imaging and R2∗ values of the cystic fluid were measured and compared between the two groups using the independent sample t-test or Mann-Whitney U-test. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of different parameters. The area under ROC curves (AUCs) was compared using the Delong test. Spearman's correlation analysis was used to assess the correlation between APTw imaging and R2∗ values. RESULTS: APTw imaging values of OE were lower, while R2∗ values were higher in OE than those in OOC (p=0.001 and < 0.001). The AUCs of APTw imaging and R2∗ values to identify OE from OOC were 0.910 and 0.975. The AUC increased to 0.990 when combining APTw imaging and R2∗ values, yet without a significant difference to the APTw imaging or R2∗ value alone (p=0.229 and 0.082, respectively). APTw imaging values were negatively correlated with R2∗ values (r=-0.522, p<0.001). CONCLUSION: Both APTw imaging and R2∗ values of OE are significantly different from other ovarian cystic lesions. APTw imaging combined with R2∗ values show excellent diagnostic efficacy to differentiate between OE and OOC.

[Investigate of the etiology and prevention status of liver cirrhosis].

Objective: To investigate the etiology, prevention and treatment status, and their corresponding regional differences of the patients with liver cirrhosis in China, in order to provide scientific basis for the development of diagnosis and control strategies in China. Methods: Clinical data of patients diagnosed with liver cirrhosis for the first time through January 1, 2018 to December 31, 2020 from 50 hospitals in seven different regions of China were collected and analyzed retrospectively, and the difference of etiology, treatment, and their differences in various regions were analyzed. Results: A total of 11 861 cases with liver cirrhosis were included in the study. Thereinto, 5 093 cases (42.94%) were diagnosed as compensated cirrhosis, and 6 768 cases (57.06%) had decompensated cirrhosis. Notably, 8 439 cases (71.15%) were determined as chronic hepatitis B-caused cirrhosis, 1 337 cases (11.27%) were alcoholic liver disease, 963 cases (8.12%) were chronic hepatitis C, 698 cases (5.88%) were autoimmune liver disease, 367 cases (3.09%) were schistosomiasis, 177 cases (1.49%) were nonalcoholic fatty liver, and 743 cases (6.26%) of other types of liver disease. There were significant differences in the incidence of chronic hepatitis B, chronic hepatitis C, alcoholic liver disease, fatty liver, schistosomiasis liver disease, and autoimmune liver disease among the seven regions (P<0.001). Only 1 139 cases (9.60%) underwent endoscopic therapy, thereinto, 718 cases (6.05%) underwent surgical therapy, and 456 cases (3.84%) underwent interventional therapy treatment. In patients with compensated liver cirrhosis, 60 cases (0.51%) underwent non-selective ß receptor blockers(NSBB), including 59 cases (0.50%) underwent propranolol and 1 case (0.01%) underwent carvedilol treatment. In patients with decompensated liver cirrhosis, 310 cases (2.61%) underwent NSBB treatment, including 303 cases (2.55%) underwent propranolol treatment and 7 cases (0.06%) underwent carvedilol treatment. Interestingly, there were significant differences in receiving endoscopic therapy, interventional therapy, NSBB therapy, splenectomy and other surgical treatments among the seven regions (P<0.001). Conclusion: Currently, chronic hepatitis B is the main cause (71.15%) of liver cirrhosis in several regions of China, and alcoholic liver disease has become the second cause (11.27%) of liver cirrhosis in China. The three-level prevention and control of cirrhosis in China should be further strengthened.

[Progress of research on evaluation indicators and standards about high-speed train comfort].

The rapid development of high-speed railway in China has proposed higher requests for the comfort level of high-speed trains. However, there is no internationally unified evaluation criterion for high-speed train comfort currently, which therefore substantially affects the comparability and standardization of research results for high-speed train comfort. This paper systematically reviews the research literature about evaluation indicators and standards related to high-speed train comfort, and finds that there is currently no unified definition, evaluation indicators, as well as evaluation criterion for high-speed train comfort. Most current evaluation criteria are based on a single indicator. Some indicators are simultaneously developed by different apartments and differ between each other, and there is no comprehensive indicator or criteria for high-speed train comfort, restricting the comparison of high-speed train comfort across regions. It is recommended that the administrative department of high-speed railroad in China should organize experts to establish a unified definition of high-speed train comfort, comprehensive evaluation indicators and relevant judgment criteria for high-speed train comfort, in face of the rapid development and globalization of high-speed trains.

[Prospective comparison of greenlight laser anatomic vaporization-incision technique and photoselective vaporization of the prostate in the treatment of benign prostatic hyperplasia].

Objective: To prospectively compare the efficacy and safety of the greenlight laser anatomical vaporization-incision technique (AVIT) and photoselective vaporization of the prostate(PVP)in the treatment of benign prostatic hyperplasia (BPH). Methods: From November 2019 to September 2020, a randomized controlled study was conducted on 136 BPH patients undergoing greenlight laser surgery in the Department of Urology, the Second Affiliated Hospital of Soochow University. The patient's age ranged from 53 to 85 years and the prostatic volume ranged from 30 to 104 ml. They were divided into two groups by random number table method,including 68 cases of AVIT(observation group)and 68 cases of PVP(control group). The clinical data of the two groups before, during and after operation were collected and analyzed. Results: Operations were successfully completed in the two groups. At 6 months after operation, 63 cases in the observation group and 66 cases in the control group completed the follow-up. There was no significant difference in the prevalence of hypertension, diabetes, coronary heart disease, atrial fibrillation and renal insufficiency between the two groups before operation (all P>0.05). The differences of preoperative age [(66.8±6.5) vs (67.3±5.4) years], international prostate symptom score (IPSS) [(24.2±4.7) vs (23.5±4.5) ], quality of life score (QOL) [4.7(4.1, 4.9) vs 4.6(4.2, 5.0)], peak urinary flow rate (Qmax) [(6.9±2.8) vs (6. 8±2.6) ml/s], post-void residual volume (PVR) [(137(52.8, 190.9) vs 119(70.6, 172.1) ml], prostate volume (PV) [70.5(60.6, 80.9) vs 68.2(61.2, 80.5) ml], serum prostate specific antigen (PSA) [4.4(3.5, 5.1) vs 4.4(3.4, 5.0) ng/ml] were not statistically significant between the two groups (all P>0.05). There was no significant difference in the amount of intraoperative blood loss, catheterization time and the postoperative hospitalization time between the two groups (all P>0.05). Compared with the control group, the operation time and lasing time of the observation group were longer[69.0(64.6, 75.0) vs 55.8(49.1, 63.4) min,(36.3±9.9) vs (31.3±9.3) min], and the intraoperaive laser energy consumption and laser energy density were higher[(297±20) vs (240±20) kJ,(4.50±1.35) vs (3.73±1.17) kJ/ml]. The differences were all statistically significant (all P<0.05). At the follow-up of 1, 3 and 6 months after operation, IPSS and QOL in the observation group were lower than those in the control group, and the differences were all statistically significant (all P<0.05). Qmax in the observation group was higher and PVR was lower than those in the control group, with statistically significant differences (P<0.05). Six months after operation, PV and PSA in the observation group decreased more significantly than those in the control group (56% vs 47%, 70% vs 60%, both P<0.05). No urethral stricture and urinary incontinence occurred in two groups after operation. The incidence rate of urinary tract irritation in the observation group was 6.3%(4/63),lower than the 18.2%(12/66)in the control group (P<0.05). There was no significant difference in the incidence rates of urinary retention, bladder neck contracture and secondary bleeding between the two groups (all P>0.05). Conclusions: Greenlight laser anatomical vaporization-incision technique is safe and effective in the treatment of BPH. Compared with PVP, AVIT has more prostate tissue removed and better curative effect, which is worthy of clinical promotion.

[Analytical performance verification protocols and performance specifications of platelet-dependent von Willebrand factor activity testing].

Objective: To investigate the analytical performance verification protocols and performance specifications of platelet-dependent von Willebrand factor (VWF) activity testing (VWF:GPIbM) for clinical laboratories. Methods: According to Clinical Laboratory Standards Institute (CLSI) documents and National Health Standard of China, the performance verification of VWF:GPIbM was designed and implemented using Sysmex CS-5100 instrument and its corresponding reagents. (1) Precision verification: Two commercial quality control samples (with normal and low activity levels) and three plasma pools (with activity range from 5.0% to 150.0%) were prepared. Each sample was tested five times daily for five consecutive days. The coefficient of variation (CV) of intra-and inter-run precisions were calculated, and the precision evaluation criterion was set according to package inserts. (2) Trueness verification: The calibrator was diluted to five reference materials with activity values of 5.2%, 31.2%, 62.4%, 104.0% and 138.7%, and each reference material was tested five times daily for five consecutive days. The bias between the measured value and the reference value was calculated, and the trueness evaluation criterion was set according to the total allowable error. (3) Linearity verification: Ten pooled plasmas with theoretical value range from 3.6% to 160.4% were prepared for the linearity verification of two calibration curves set by the manufacturer (i.e. low range and normal range calibration curve). Each pooled plasma was tested three times in a single run. The slope and R2 of linear regression of mean of measured value and theoretical value, as well as bias, were calculated, and the linearity evaluation criterion was set according to National Health Standard of China and package inserts. (4) Limit of quantitation verification: The calibrator was diluted to two reference materials with activity values of 3.3% and 2.7%, and each material was tested twelve times. The limit of quantitation evaluation criterion was set according to CLSI document. Results: The CVs of intra-and inter-run were 1.0%-2.5% and 1.1%-2.6%, respectively. The biases of trueness verification were -0.4%, 1.0%, -2.6%, 0.3% and -2.7%, respectively. The linearity verification results of low range (3.6%-31.8%) and normal range (28.4%-160.4%) showed that the slopes of regression equation were 1.021 7 and 0.996 2, respectively, R2 were 0.993 5 and 0.993 9, respectively, and the biases with 0-1.8% and -10.1%-0 of plasmas met the criterion. The biases ranged from -0.4% to 0.3% of test results in the verification of limit of quantitation met the criterion. Conclusion: The verification results of VWF:GPIbM assay for precision, trueness, linearity and limit of quantification meet the performance requirements indicated in the package inserts and the criteria set in this study, which can be taken as a reference of performance verification for the clinical laboratories.

[Research progress of micronucleus visualization analysis and artificial intelligence detection strategy].

The micronucleomics test can comprehensively display a variety of harmful endpoints, such as DNA damage and repair, chromosome breakage or loss and cell growth inhibition, with fast, simple and economical feature. Micronucleomics is not only widely used in the comprehensive assessment of the types and modes of genetic action of exogenous chemicals (such as drugs, food additives, cosmetics, environmental pollutants, etc.), but also plays an important role in the screening and risk assessment of cancer population at high risk. However, the traditional micronucleomics image counting method has the characteristics of time-consuming, low accuracy, and high cost, which cannot meet the current analysis requirements of large-scale, multi-index, rapidity, high precision and visualization. In recent years, with the rapid development of the era of precision medicine based on big data, visualized analysis of new micronucleomics based on machine learning and detection strategies based on deep learning have shown a good application prospect. This review, based on the application value of micronucleomics, systematically compares the traditional and new artificial intelligence counting of micronucleus images, and discusses the future direction of micronucleus image detection.

[Prediction on the cardio-cerebrovascular death and probability of premature death caused by common risk factors in China in 2030].

Objective: Predictive models were used to evaluate the impact of common risk factors on the number of cardio-cerebrovascular deaths and the probability of premature death. Methods: Using the data for China estimated by the Global Burden of Disease study 2015 (GBD 2015), we calculated the population attribution fraction (PAF) of risk factors. The proportional change model was used to estimate the number of unattributable deaths by 2030, and to predict the number of deaths, mortality, standardized mortality and probability of premature death by 2030. Results: According to the natural change trend of risk factors from 1990 to 2015, the number of deaths and mortality would reach 6.12 million and 428.53/100 000 by 2030, with an increase of 59.92% and 52.87%. By 2030, the probability of premature death from cardio-cerebrovascular diseases among Chinese aged 30-70 years old would continue to decline, from 11.43% to 11.28% for men, and from 5.79% to 4.43% for women. If the goals of all included risk factors were reached by 2030, 2 289 200 cardio-cerebrovascular deaths would be avoided. If only the exposure to a single risk factor was achieved by 2030, blood pressure, total cholesterol, and fine particulate matter exposure were the three most important factors affecting cardio-cerebrovascular deaths, which would reduce 1 332 800, 609 100 and 306 800 deaths, respectively. Among the involved risk factors, the control of blood pressure would mostly decrease the number of deaths due to ischemic heart disease and hemorrhagic stroke, about 677 300 and 391 100 deaths, accordingly. Conclusion: The control of risk factors is of great significance in reducing deaths and probability of premature death due to cardio-cerebrovascular diseases. If the control targets of all risk factors could be achieved by 2030, the burden of cardio-cerebrovascular diseases would be reduced greatly.

The inhibition of the breast cancer by PPARγ agonist pioglitazone through JAK2/STAT3 pathway.

Breast cancer, especially triple-negative breast cancer, is one of the deadliest cancers in women. To date, there is a lack of a good therapeutic regimen for it. PPARγ has been reported to be a tumor suppressor and could be activated by many agonists involved in cancer inhibition. Therefore, the expression of PPARγ in breast cancer was analyzed by online software UALCAN whose data were from the TCGA database. The results revealed that the PPARγ expression was reduced in breast cancer tissues. Furthermore, the methylation in the PPARγ promoter was also assayed and the results indicated that the methylation level in the PPARγ promoter in breast cancer tissue was higher than that in normal tissue. In order to verify the methylation in promoter involved in the regulation of gene PPARγ expression, the 5'-Aza and fluorescence assays were performed and the results proved that methylation in promoter participated in gene PPARγ expression regulation. Pioglitazone, a PPARγ agonist, still was not investigated in breast cancer. Therefore, the effects of pioglitazone on breast cancer cells were tested by cell viability, scratch and transwell assays, and results indicated that the pioglitazone has the inhibition effect on the proliferation and migration of breast cancer cells by PPARγ which was correlated with the JAK2/STAT3 pathway. In order to further confirm the inhibition effect of pioglitazone on breast cancer in vivo, the nude mice model was administrated by gavage with pioglitazone. And the results indicated that pioglitazone could inhibit the growth of breast cancer in the PPARγ overexpression group in vivo. In summary, the expression of gene PPARγ was decreased in breast cancer tissues, which was correlated with its methylation in the promoter region. Moreover, pioglitazone could exert its inhibition on breast cancer proliferation and migration by the JAK2/STAT3 pathway.

[Performance of human papillomavirus typing test in cervical precancer lesions and cervical cancer screening].

Objective: To evaluate the performance of Hybribio human papillomavirus (HPV) typing test kit for high risk HPV-DNA typing detection in screening of cervical precancer lesions. Methods: A total of 9 914 women were recruited in Henan, Shanxi, and Guangdong provinces from June to July 2017. All women underwent HPV DNA test. The women who diagnosed as HPV positive and cytological examination ≥ atypical squamous cells of undetermined significance (ASCUS) or HPV negative and cytological examination≥low-grade squamous intraepithelial lesions (LSIL) underwent colposcopy biopsy and pathological examination. Using the pathological diagnosis as the gold standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and 95% confidence interval (CI) of high-risk HPV and HPV16/18 tests were calculated. Results: The mean age of 9 914 subjects was (45.0±9.3) years old. Among them, 1 302 subjects were detected as high risk HPV positive, including 211 of HPV16 positive and 64 of HPV18 positive. According to the pathological gold standard of cervical intraepithelial neoplasia grade 2 (CIN2) or worse, the sensitivity and specificity of high risk-HPV and HPV 16/18 for triaging ASCUS women were 90.6% (95%CI: 75.8%-96.8%) and 78.0% (95%CI: 74.5%-81.2%) as well as 56.3% (95%CI: 39.3%-71.8%) and 95.7% (95%CI: 93.8%-97.1%), respectively. The sensitivity and specificity of high risk-HPV and HPV 16/18 for cervical precancer lesions screening were 95.1% (95%CI: 88.1%-98.1%) and 87.6% (95%CI: 86.9%-88.2%) as well as 65.9% (95%CI: 55.1%-75.2%) and 97.8% (95%CI: 97.5%-98.1%), respectively. Conclusions: The Hybribio HPV test kit has a relative high sensitivity and specificity for cervical precancer lesions screening and ASCUS triaging. It is reliable for HPV DNA detection and cervical cancer screening.

[Influence of oxidative/antioxidative biomarkers and inflammatory cytokines on rats after sub-acute orally administration of titanium dioxide nanoparticles].

OBJECTIVE: To evaluate the sub-acute oral effect of titanium dioxide (TiO2) nanoparticles on the oxidation/antioxidation biomarkers and inflammatory cytokines in blood, liver, intestine, and colon in rats. METHODS: Twenty four 4-week-old clean-grade Sprague Dawley (SD) rats were randomly devided into 4 groups by body weight (n=6, control, low, middle, and high), in which the rats were orally exposed to TiO2 nanoparticles at doses of 0, 2, 10 and 50 mg/kg body weight/day for 28 consecutive days separately. Food intake, body weight and abnormal behaviors during the experiment were recorded. The rats were euthanized on the 29th day. The blood was collected via abdominal aortic method and centrifuged to collect the serum. Tissues from liver, intestine and colon were collected and homogenated. Then enzyme-linked immunosorbent assay (ELISA) and microwell plate methods were used to detect oxidation/antioxidation biomarkers including superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), total mercapto (T-SH), glutathione disulfide (GSSG), malomdialdehvde (MDA) and inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the serum, liver, intestine and colon in the rats. RESULTS: Compared with the control group, no significant differences in body weight, food intake and organ coefficients were observed in all the three groups after TiO2 gavage. No significant changes in GSH, GSH-Px, T-SH, and IL-6 were observed. Compared with the control group, significant increase of SOD activity in serum in high dose group, signi-ficant increase of GSSG concentration in intestine in middle and high dose group and significant increase of MDA concentration in liver in low and high dose group were observed. Compared with the control group, a significant increase of TNF-α in liver in middle and high dose group was observed. CONCLUSION: TiO2 nanoparticle can increase antioxidant enzymes activities in blood, increase oxidative biomarkers in liver and intestine, increase inflammatory cytokines in liver in rats after a 28-day sub-acute orally administration. Among blood, liver, intestine, and colon, liver is most sensitive to the toxicity induced by TiO2 nanoparticles, followed by intestine, blood, and colon in sequence.

[Clinical application of the simultaneous detection of methotrexate and 7-hydroxymethotrexate in the delayed elimination for pediatric acute lymphoblastic leukemia].

Objective: To discuss the application value of the simultaneous determination of methotrexate (MTX) and 7-hydroxymethotrexate (7-OHMTX) in the delayed elimination of MTX for pediatric acute lymphoblastic leukemia (ALL). Methods: Cross sectional study. A total of 97 children who received 192 high-dose MTX treatments cycles in Lu Daopei Hospital from April to August 2019 were enrolled. The peripheral blood was collected at 0,24,48 h after the end of MTX infusion and analyzed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). One hundred and ninety-two MTX treatments were divided into a normal MTX elimination group (n=149) and delayed elimination group (n=43) according to the standard of delayed elimination and divided into 0-9 year old group (n=95), 10-14 group (n=50), 15-18 group (n=47) according to age. The comparisons of the C(MTX), C(7-OHMTX) between normal and delayed group was conducted as well as among different age groups. Receiver operator characteristic curve (ROC) of C(MTX-0h) and C(7-OHMTX-0h) was analyzed and the concentration corresponding to the maximum of the Youden index on the ROC was set as the warning value for delayed elimination. Correlation between the delayed elimination after the end of MTX infusion and toxicity was investigated and the percentage of delayed elimination was also analyzed. Results: The concentrations of MTX and 7-OHMTX were significantly higher in the delayed elimination group than the normal group. Immediately after infusion (0 h), a C(7-OHMTX-0h) of >17.8 µmol/L (sensitivity 97.7%, specificity 54.4%) and a C(MTX-0h) of >148.8 µmol/L (sensitivity 72.1%, specificity 84.6%) were found to be warning predictors of delayed elimination under the MTX treatment protocol. MTX delayed elimination was positively correlated with methotrexate-induced toxicities (r=0.58, P<0.01). The percentage of hepatotoxicity and nephrotoxicity was 32.6% and 37.2% in the delayed elimination group, which was significantly higher than normal group of 12.8% and 3.4% (P<0.05). No significant difference was found in other toxicities. There was significant difference in C(MTX) among different age groups but no significant difference in C(7-OHMTX). Conclusion: Simultaneously determination of MTX and 7-OHMTX in plasma by HPLC-MS/MS in childhood ALL patients can provide a reference for clinical individualized medicine and pharmacokinetic research.

[Expression of HMGB1 protein in breast cancer and its clinicopathological significance].

Objective: To investigate the expression and clinicopathological significance of high mobility group box protein B1 (HMGB1) protein in breast cancer. Methods: The expression of HMGB1 protein in 26 normal breast tissues and 417 invasive breast cancer tissues diagnosed at Dongyang People's Hospital, Zhejiang Province from 2016 to 2018 were detected by immunohistochemical EnVision method. The relationship between nuclear and cytoplasmic HMGB1 protein expression and clinicopathologic features of breast cancer patients were analyzed. Results: The nuclear and cytoplasmic expression of HMGB1 protein was 80.8% (337/417) and 16.8% (70/417) respectively in breast cancer, and was 46.2%(12/26) and 0(0/26) respectively in normal breast tissue. Both nuclear and cytoplasmic expression of HMGB1 protein in breast cancer were significantly higher than normal breast tissue (P<0.001, P=0.046, respectively). The nuclear expression of HMGB1 protein was also higher in high grade, estrogen receptor (ER) negative, progesterone receptor (PR) negative (P=0.006, P=0.004, P<0.001, respectively); whereas the cytoplasmic expression of HMGB1 protein was also higher in high grade, estrogen receptor (ER) negative, progesterone receptor (PR) negative (P<0.001 in all) breast cancers. Multivariate logistic regression model showed that nuclear HMGB1 expression correlated with histologic grade (OR=2.188, 95%CI=1.078-4.443, P=0.030), while cytoplasmic HMGB1 expression correlated with histologic grade (OR=3.031, 95%CI=1.600-5.742, P=0.001), ER (OR=0.129, 95%CI=0.034-0.494, P=0.003) and TNM staging (OR=3.820, 95%CI=1.042-14.001, P=0.043). Multivariate analysis of Cox proportional hazard model showed that nuclear HMGB1 expression was an independent risk factor for the overall survival of breast cancer patients (HR=0.366, 95%CI=0.138-0.972, P=0.044). Conclusion: Nuclear and cytoplasmic HMGB1 proteins are related to multiple poor prognostic factors in breast cancer, and may be a potential biomarker for breast cancer treatment.

[The expanding needs on lipid-lowering treatment in patients with acute coronary syndrome by applying newly issued definition of extreme high-risk by Chinese Society of Cardiology].

Objective: To assess the expanding needs on lipid-lowering treatment in patients with acute coronary syndrome (ACS) by applying newly issued definition of extreme high-risk, which is proposed by Chinese expert consensus on lipid management of extreme high-risk atherosclerotic cardiovascular disease (ASCVD) patients of Chinese Society of Cardiology (CSC). Methods: Data of this study was derived from the Improving Care for Cardiovascular Disease in China (CCC) project, which was a case-based nationwide registry study and launched as a collaborative initiative by the American Heart Association and the CSC. The project consecutively recruited ACS patients from158 tertiary hospitals and 82 second hospitals across China, and detailed clinical information of patients was collected. This study enrolled ACS inpatients in CCC project from November 2014 to July 2019. The proportion of extreme high-risk patients, their characteristics, mean LDL-C levels at admission, the gap between measured LDL-C level and the new target, and lipid-lowering therapy at discharge were assessed. Results: Among 104 516 ACS inpatients enrolled in this study, 75.1% (78 527/104 516) met the criteria of extreme high-risk and were expected to achieve the new LDL-C goal. Among patients at extreme high-risk, 21.2% (16 651/78 527) had multiple severe ASCVD events and 78.8% (61 876/78 527) had 1 severe ASCVD event and at least two high-risk factors. For the extreme high-risk patients, the mean level of LDL-C at admission was (2.8±1.0) mmol/L, prevalence of LDL-C ≥1.4 mmol/L was 93.4% (73 307/78 527) and the median gap between LDL-C level at admission and the target of 1.4 mmol/L was 1.3 (0.8, 2.0) mmol/L. If LDL-C could be further reduced to 50% of the admission level, we estimated that 55.6% (43 632/78 527) of the extreme high-risk patients would achieve the new LDL-C goal. Among 40 875 patients with information about discharge statin dosage, 93.5% (28 004/29 947) of the extreme high-risk patients were prescribed with statins at discharge, and among them 95.1% (26 632/28 004) received statin monotherapy and 91.1% (25 501/28 004) were at moderate doses of statins. Conclusion: About three fourth of inpatients with ACS were categorized as extreme high-risk based on the new definition of CSC expert consensuses, nine out of ten patients at extreme high-risk didn't achieve the new LDL-C target at admission, and the intensity of lipid-lowering therapy was insufficient in clinical practice. There are substantially expanding needs for implementing more intensive and effective lipid-lowering strategies.

[Association between smoking and the severity of coronary lesions among young and middle-aged female patients with acute coronary syndrome].

Objective: To investigate the association between smoking and the severity of coronary lesions among young and middle-aged female patients with acute coronary syndrome (ACS). Methods: Data of this study were derived from the Improving Care for Cardiovascular Disease in China (CCC)-ACS project, a collaborative study of the Chinese Society of Cardiology and the American Heart Association. Since 2014, the CCC-ACS project consecutively enrolled inpatients with ACS, systematically collected their clinical data and evaluated medical quality of these patients from 158 tertiary hospitals and 82 secondary hospitals across China. This study enrolled female patients less than 60 years old with initial ACS, who received coronary angiography in CCC-ACS project. Patients were divided into two groups according to smoking status. A multivariate logistic regression analysis was used to analyze the association between smoking and the severity of coronary lesions among young and middle-aged female patients with ACS. Results: A total of 2 863 female patients younger than 60 years old with initial ACS, who received coronary angiography, were enrolled. Among them, 12% (340 cases) was smokers. Proportion of patients younger than 45 years old was higher (13.2% (45/340) vs. 8.5% (215/2 523), P<0.01) and prevalence of hypertension (59.4% (202/340) vs. 66.7% (1 683/2 523), P<0.01) and diabetes (39.4% (134/340) vs. 44.2% (1 116/2 523), P=0.09) was lower in smoker group than in non-smoker group. However, prevalence of ST-elevation myocardial infarction (66.8% (227/340) vs. 53.7% (1 354/2 523), P<0.01), coronary multi-vessel lesions (39.1% (133/340) vs. 32.6% (822/2 523), P<0.01) and severe stenosis in either single-vessel (56.2% (109/194) vs. 46.1% (706/1 530), P<0.01) or multi-vessel (63.2% (84/133) vs. 58.2% (478/822), P=0.29) was significantly higher in smoker group than in non-smoker group. Multivariate logistic regression analyses showed that after adjusting for age, hypertension, diabetes, elevated low-density lipoprotein cholesterol, lower high-density lipoprotein cholesterol, elevated triglyceride, renal insufficiency, family history of coronary heart disease and types of ACS, smokers faced a higher risk of coronary multi-vessel lesions, coronary multi-vessel severe lesions and coronary severe lesions with the odds ratios and 95% confidence interval of 1.41 (1.11-1.79), 1.40 (1.10-1.78) and 1.78 (1.11-2.87), compared with non-smokers. Conclusions: Smoking is significantly associated with an increased risk of extensive and severe coronary lesions among young and middle-aged female patients with ACS. This study provides crucial evidence for further understanding the harms of smoking and the need to strengthen the tobacco control education and smoking cessation guidance for young and middle-aged women.

Anti-epidermal growth factor receptor (EGFR) monoclonal antibody combined with cisplatin and 5-fluorouracil in patients with metastatic nasopharyngeal carcinoma after radical radiotherapy: a multicentre, open-label, phase II clinical trial.

BACKGROUND: We conducted a single-arm phase II trial to evaluate the efficacy and adverse effects (AEs) of an anti-epidermal growth factor receptor monoclonal antibody, nimotuzumab, combined with cisplatin and 5-fluorouracil (PF) as first-line treatment in recurrent metastatic nasopharyngeal carcinoma after radical radiotherapy. METHODS: Patients who met the eligibility criteria were recruited from ten institutions (ClinicalTrials.gov; NCT01616849). A Simon optimal two-stage design was used to calculate the sample size. All patients received weekly nimotuzumab (200 mg) added to cisplatin (100 mg/m2 D1) and 5-fluorouracil (4 g/m2 continuous infusion D1-4) every 3-weekly for a maximum of six cycles. Primary end point was objective response rate (ORR). Secondary end points included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and AEs. RESULTS: A total of 35 patients were enrolled (13 in stage 1 and 22 in stage 2). Overall ORR and DCR were 71.4% (25/35) and 85.7% (30/35), respectively. Median PFS and OS were 7.0 (95% CI 5.8-8.2) months and 16.3 (95% CI 11.4-21.3) months, respectively. Unplanned exploratory analyses suggest that patients who received ≥2400 mg nimotuzumab and ≥4 cycles of PF had superior ORR, PFS and OS than those who did not (88.9% versus 12.5%, P < 0.001; 7.4 versus 2.7 months, P = 0.081; 17.0 versus 8.0 months, P = 0.202). Favourable subgroups included patients with lung metastasis [HROS 0.324 (95% CI 0.146-0.717), P = 0.008] and disease-free interval of >12 months [HROS 0.307 (95% CI 0.131-0.724), P = 0.004], but no difference was observed for metastatic burden. The only major grade 3/4 AE was leukopenia (62.9%). CONCLUSION: Combination nimotuzumab-PF chemotherapy demonstrates potential efficacy, and is well tolerated as first-line chemotherapy regimen in recurrent metastatic nasopharyngeal carcinoma.

Q-switched Dy:ZBLAN fiber lasers beyond 3 µm: comparison of pulse generation using acousto-optic modulation and inkjet-printed black phosphorus.

We report high-energy mid-infrared pulse generation by Q-switching of dysprosium-doped fiber lasers for the first time. Two different modulation techniques are demonstrated. Firstly, using active acousto-optic modulation, pulses are produced with up to 12 µJ energy and durations as short as 270 ns, with variable repetition rates from 100 Hz to 20 kHz and central wavelengths tunable from 2.97 to 3.23 µm. Experiments are supported by numerical modeling, identifying routes for improved pulse energies and to avoid multi-pulsing by careful choice of modulator parameters. Secondly, we demonstrate passive Q-switching by fabricating an inkjet-printed black phosphorus saturable absorber, simplifying the cavity and generating 1.0 µJ pulses with 740 ns duration. The performance and relative merits of each modulation approach are then critically discussed. These demonstrations highlight the potential of dysprosium as a versatile gain medium for high-performance pulsed sources beyond 3 µm.

Promising High-Confinement Regime for Steady-State Fusion.

A reproducible stationary high-confinement regime with small "edge-localized modes" (ELMs) has been achieved recently in the Experimental Advanced Superconducting Tokamak, which has a metal wall and low plasma rotation as projected for a fusion reactor. We have uncovered that this small ELM regime is enabled by a wide edge transport barrier (pedestal) with a low density gradient and a high density ratio between the pedestal foot and top. Nonlinear simulations reveal, for the first time, that the underlying mechanism for the observed small ELM crashes is the upper movement of the peeling boundary induced by an initial radially localized collapse in the pedestal, which stops the growth of instabilities and further collapse of the pedestal, thus providing a physics basis for mitigating ELMs in future steady-state fusion reactors.