Background: Chemoresistance and tumor recurrence remain major obstacles in colorectal cancer (CRC) therapy. Elucidating the molecular mechanisms underlying treatment resistance is critical for improving therapeutic outcomes. Methods: We analyzed transcriptomic profiles from public datasets (TCGA and GSE39582) to identify differentially expressed genes associated with a poor response to neoadjuvant chemotherapy in CRC patients. Among 298 candidate genes, ANXA9 emerged as significantly overexpressed in chemoresistant tumors and associated with a poor prognosis. These findings were further validated in an independent cohort of 146 Stage III CRC patients using immunohistochemistry and survival analysis. The expression of ANXA9 was evaluated in oxaliplatin acquired-resistant CRC cell lines via qPCR and Western blot. Functional studies, including RNA interference, colony formation, apoptosis assays, and drug sensitivity testing, were performed in vitro and in vivo to assess the role of ANXA9. A high-throughput drug screen identified G749, a FLT3 inhibitor, as a potential therapeutic agent. Results: ANXA9 expression was significantly elevated in non-responders to chemotherapy and oxaliplatin-resistant CRC cell lines. The knockdown of ANXA9 reduced proliferation and enhanced oxaliplatin sensitivity. G749 was found to suppress ANXA9 expression in a dose-dependent manner and inhibit CRC cell growth in vitro and in patient-derived organoids. In a CRC xenograft mouse model, G749 reduced the tumor burden without observable toxicity. Mechanistically, we identified ZMYM2 as a transcriptional regulator of ANXA9. ChIP-qPCR confirmed ZMYM2 binding to the ANXA9 promoter, especially in resistant cells. Silencing ZMYM2 suppressed tumor cell growth and restored chemosensitivity. Conclusions: The ZMYM2-ANXA9 signaling axis drives chemoresistance and tumor progression in CRC. FLT3 inhibition by G749 effectively downregulates ANXA9 and sensitizes tumors to chemotherapy, highlighting a novel therapeutic approach for chemoresistant CRC.

The spatio-temporal sequence of human body movements provides important information about daily action patterns. This article presents a pyroelectric infrared (PIR) sensor array for detecting human motion features and develops a bidirectional long short-term memory (LSTM) neural network for sequence recognition. A PIR sensor array with five direction-sensitive modules is proposed to detect the changing infrared field induced by the human head, upper limb, and lower limb. The low-dimensional output of the sensor array is directly fed to a multi-layer bidirectional LSTM-based neural network for sequential dependency learning. A PIR data set of seven daily actions is generated by four subjects imitating the predefined movements. Experimental results demonstrate that the presented approach achieves high accuracy in action recognition.

Radio tomographic imaging (RTI) is a computational imaging technique that estimates the distribution of shadowing loss caused by obstructions in a monitored area using received signal strength (RSS) measurements between radio frequency (RF) network nodes. However, finding a solution to RTI under noise interference is generally an ill-posed inverse problem, and additional measures are required to reduce noise and achieve the desired image properties. The sparse distribution of targets in the monitored areas is intuitively an important prior for accurate image reconstruction. In this article, we propose a Gini index (GI)-based sparse reconstruction approach for RTI that fully leverages sparsity for high-quality imaging. Based on the linear cumulative shadowing model, RTI is formulated using the classical GI from economics as the sparsity measure to construct the optimal objective function. The GI-based objective function is quasi-convex, and RTI is solved by the simultaneous perturbation stochastic approximation (SPSA) algorithm. Experimental studies in three different environments are conducted to validate the superior performance of the proposed approach with respect to commonly used regularization and sparsity measures.

Background Postoperative sore throat is a frequent adverse event after double-lumen endobronchial tube (DLT) intubation. The aim of this study was to investigate whether esketamine gargle has a preventive effect on the incidence of postoperative sore throat in patients undergoing DLT intubation. Methods This trial included 140 patients undergoing elective thoracic surgery at the third affiliated hospital of Sun Yat-Sen University. Patients were randomly allocated into the following two groups of 70 patients each: the control group, gargling with saline of 30 mL, and the esketamine group, gargling with an esketamine solution of 30 mL (2 mL/50 mg esketamine in 28 mL saline), 5 min prior to anaesthesia induction. The primary outcome was the incidence of sore throat 24 h after surgery. The main secondary outcomes included the incidence of sore throat and hoarseness at 1 h and 48 h after surgery, as well as the intraoperative haemodynamic responses. Results The incidence of sore throat was significantly higher in the control group (47.1%, 33/70 patients) compared with the esketamine group (12.9%, 9/70 patients) at 24 h after surgery (RD, 0.41; 95% confidence interval, 0.26–0.57; p < 0.001). Furthermore, the incidence of sore throat at 1 h (p = 0.027), 24 h (p = 0.019), and seventh day (p = 0.031) as well as hoarseness at 1 h (p = 0.027), 24 h (p = 0.019), and 48 h (p = 0.031) after surgery were reduced in the esketamine group. Significant differences were seen in the peak levels of systolic blood pressure, mean arterial blood pressure, and heart rate between the groups during the intubation (p < 0.05). Besides, no patient developed an adverse reaction to esketamine. Conclusion Preoperative gargling of esketamine can provide an effect against sore throat after DLT intubation without adverse side effects and effectively inhibit sharp elevations in heart rate and blood pressure during double-lumen intubation procedures.

OBJECTIVE:To evaluate the efficacy of poly ADP ribose polymerase (PARP) inhibitors (PARPis) in breast and ovarian cancer with BRCA (BReast CAncer susceptibility gene) mutation (BRCAm).METHODS:We conducted a meta-analysis of randomized controlled, phase II or III trials by searching of electronic databases from inception to September 1, 2020. The efficacy of PARPis measured by hazard ratios (HRs) and 95% confidence intervals (95% CIs) for progression free survival (PFS) and overall survival (OS) of patients.RESULTS:By addition of PARPis to conventional therapy, breast or ovarian cancer patients carrying BRCAm significantly benefited PFS (breast cancer: HR 0.64, 95% CI=0.55-0.75, P<0.001; ovarian cancer: HR 0.33, 95% CI=0.27-0.42, P<0.001), but OS of patients did not increase significantly in these two cancer types (breast cancer: HR 0.87, 95% CI=0.76-1.01, P=0.065; ovarian cancer: HR 0.78, 95% CI=0.61-1.01, P=0.058). For ovarian cancer patients carrying BRCAm, the use of therapy with PARPis yielded longer PFS at the stage of newly diagnosed than the stage of recurrence (22.5 months vs 9.6 months).CONCLUSION:PARPis were beneficial to all with BRCAm, but they were "most" beneficial to the ovarian cancer subset when administered early after diagnosis, rather than after recurrence.

Objective To compare the fracture risk in postmenopausal Asian women with or without type 2 diabetes mellitus (T2DM). Methods The study cohort comprised data from consecutive postmenopausal women with T2DM that were retrieved from a prospectively maintained institutional database from 2001 to 2009. Postmenopausal women without DM from the Medical Examination Center from 2001 to 2009 formed the control cohort. The primary endpoint was the World Health Organization Fracture Risk Algorithm (FRAX, revised 2013) score. The secondary endpoint was bone mineral density (BMD). Results There were 1014 individuals included for the assessment (T2DM, n=500 and non-DM, n=514). Based on the FRAX model, the risk of major osteoporotic fractures and hip fractures over the next 10 years was higher in the T2DM group compared with the non-DM group. Compared with the T2DM group, the non-DM group had a lower BMD. After adjusting for age, gender, history of alcohol consumption, smoking status, body mass index, and low-density lipoprotein, the differences were statistically significant. Conclusions Compared with postmenopausal women without DM, postmenopausal women with T2DM had a significantly higher fracture risk calculated using the FRAX model. Early intervention for postmenopausal women with T2DM may be necessary, although T2DM is associated with a high BMD.

目的 通过对西安市猕猴桃进行系统的农药残留情况及膳食暴露风险分析,明确猕猴桃农药残留风险状况.方法 对2018年西安市周至县14个猕猴桃主产乡镇共200批次样品进行农药残留定量检测分析,用每日允许摄入量和急性参考剂量进行慢性膳食摄入风险评估和急性膳食摄入风险评估,利用猕猴桃大份餐、每日允许摄入量和人均参考体重计算最大残留限量估计值.并参照兽药残留风险排序矩阵方法(英国兽药残留委员会)对农药和样品进行风险排序.结果 200个猕猴桃样品中有137个样品检出了农药残留,未有超标农药和禁用农药检出;在检出的14种农药中,慢性膳食摄入风险和急性膳食摄入风险均值远远小于100％;将14种检出农药按照风险得分分为Ⅲ类,第I类为高等风险农药,共1种;第Ⅱ类为中等风险农药,共0种;第Ⅲ类为低等风险农药,共有13种;以风险指数排序,低风险样品占35.5％,极低风险样品占64.5％,检出农药残留种类为3个以上的样品有占比5.5％,检出农药残留种类为1～2个的样品占比61.5％,未检出农药残留有66个样品,占比33％.结论 西安市周至县猕猴桃农药残留处于低风险状态,但仍然要加强日常监管工作.

BACKGROUND:Interleukin-1 (IL-1) played a role in the occurrence and development of atherosclerosis and cardiovascular events. However, the association between IL-1 blockage treatment and reducing of cardiovascular risk remains poorly defined.HYPOTHESIS:IL-1 blockage treatment reduce the risk and incidence rate of overall major adverse cardiovascular events (MACE), all-cause death, acute myocardial infarction(MI), unstable angina and heart failure.METHODS:We performed a search of published reports by using MEDLINE database (January 1, 2005 to April 1, 2018). The randomized controlled trials (RCTs) that reported sample size and occurrence numbers in test group and placebo group for the associations of interest were included.RESULTS:Eight RCT studies involving 15 647 participants were identified. Compared with those who took no IL-1 blockage, patients taking IL-1 blockage experienced a decreased risk of overall MACE (RR 0.88, 95% CI 0.82-0.94), unstable angina (RR 0.80, 95% CI 0.66-0.98), and breakthrough or recurrence of heart failure (RR 0.44, 95% CI 0.22-0.87). No association was found between IL-1 blockage treatment and death from all cause (RR 0.91, 95% CI 0.83-1.00) as well as acute MI (RR 0.85, 95% CI 0.71-1.01). The RRs associated with overall MACE, death from all cause, acute MI, and unstable angina for anakinra were 1.05, 1.16, 2.97, and 0.56, respectively, and for canakinumab were 1.05, 0.91, 0.80, and 0.80, respectively.CONCLUSIONS:Administration of IL-1 blockage was associated with decrease risks of overall MACE, unstable angina, and breakthrough or recurrence of heart failure, but not with death from all cause as well as acute MI.

Objective: To reflectively look at the present methods by which the clinical competence of 5th-year medical students (i.e. interns) in Sun Yat-Sen University (SYSU) are assessed upon finishing internship rotation in internal medicine (IM). Methods: Current procedures for the competence assessment of end-of-rotation IM interns in the First Affiliated Hospital of SYSU were reviewed, along with a point-by-point appraisal based on the PROFILE approach to structured assessment, and, whenever possible, suggestions for future improvement. Results and discussions: On a scale of 1-10, with 10 being the best or the most ideal, our marks for current methods to assess end-of-rotation IM interns in terms of being Programmatic, Real-World, Outcome-based, Formative, Impactful, Learner-engaged, and Evaluation-guaranteed were 7, 9, 3, 4, 6, 8, and 1, respectively. The strengths, weaknesses as well as potential solutions in each of the seven aspects are also discussed separately. Conclusions: Current assessment program for IM internship is strong in being programmatic, real-world, educationally impactful and learner engaged, and has room for further improvement in its time-based arrangements, relative shortage of feedback provision, as well as a systematic lack of quality control measures.

This article reports the findings of a radio received signal strength (RSS) based biometric sensing approach for lightweight walker recognition. A vertically deployed radio sensing network is designed to obtain the movement of walker at seven different heights. The sequential RSS at each height contributes weak distinguished feature to walker's identify. The human subjects are recognized by vector quantization (VQ) in the context of path-constrained walking. There are 12 walkers participated in this experiment, and the recognition accuracy is evaluated in line-of-sight and non-line-of-sight environments with four different sizes of codebooks. Experimental analysis shows the proposed sensing method can achieve the average recognition accuracy of 88.92% in line-of-sight environment better than the 74.41% in non-line-of-sight environment.

This article presents a preliminary research on radio tomographic imaging (RTI) based approach for three-dimensional static body posture sensing. A wireless network organized by a multi-level of radio frequency (RF) sensor array is introduced for posture sensing covering a three-dimensional space. It is assumed the statistical shadowing losses on the passing links between pairs of nodes will be attenuated by the occlusion body. Then an attenuation tomographic image of body posture can be obtained by using the received signal strength (RSS) measurements. Considering the property of spatial piecewise constant of body, total variation (TV) minimization is used to reconstruct the three-dimensional gray image of posture. Experimental studies show the proposed method is able to reconstruct three-dimensional body with several kinds of posture, which will bring significant benefits for future behavior analysis as well as many other applications.

Purpose Differentiating between atrioventricular nodal reentrant tachycardia (AVNRT) and non-reentrant junctional tachycardia (JT) is difficult but highly necessary for catheter ablation. The purpose of this study was to investigate whether the ventriculoatrial (VA) relationship after atrial overdrive pacing (AOP) could help to distinguish AVNRT from JT. Methods Thirty-eight AVNRT and 21 JT patients who were induced by infusion of isoproterenol after successful AVNRT ablation were paced through the high right atrium or coronary sinus until the ventricles were constantly captured. After the pacing was stopped, the intervals of postpacing VA (VA P ) and tachycardia VA (VA T ) were measured if the pacing did not terminate tachycardia. Results Thirty-five (92.1 %) cases were captured by 119 AOPs (119/175) without terminating tachycardia in the 38 cases of AVNRT. Of the 35 cases, 34 (97.1 %) showed VA P -VA T < 22.55 ms in all successful AOPs (116 times). The remaining case showed VA P -VA T > 294.9 ms in one AOP and VA P -VA T < 22.55 ms in two AOPs. All 21 JT cases could be captured successfully by all (105/105) AOPs and showed VA P -VA T > 294.9 ms. VA P -VA T < 22.55 ms had 118/118 (100 %) specificity for AVNRT, and the VA P -VA T > 294.9 ms response was 105/105 (100 %) sensitive for JT. Conclusions The VA relationship after AOP could help distinguish AVNRT from JT. VA P -VA T < 22.55 ms was specific for AVNRT, and VA P -VA T > 294.9 ms for JT in the overwhelming majority, except for the rare instance of AVNRT with a double ventricular response.

BACKGROUND Large cohort studies provide conflicting evidence regarding the potential for oral macrolide antibiotics to increase the risk of serious cardiac events.OBJECTIVES This study performed a meta-analysis to examine the link between macrolides and risk of sudden cardiac death (SCD) or ventricular tachyarrhythmias (VTA), cardiovascular death, and death from any cause.METHODS We performed a search of published reports by using MEDLINE (January 1, 1966, to April 30, 2015) and EMBASE (January 1, 1980, to April 30, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included.RESULTS Thirty-three studies involving 20,779,963 participants were identified. Patients taking macrolides, compared with those who took no macrolides, experienced an increased risk of developing SCD or VTA (RR: 2.42; 95% CI: 1.61 to 3.63), SCD (RR: 2.52; 95% CI: 1.91 to 3.31), and cardiovascular death (RR: 1.31; 95% CI: 1.06 to 1.62). No association was found between macrolides use and all-cause death or any cardiovascular events. The RRs associated with SCD or VTA were 3.40 for azithromycin, 2.16 for clarithromycin, and 3.61 for erythromycin, respectively. RRs for cardiovascular death were 1.54 for azithromycin and 1.48 for clarithromycin. No association was noted between roxithromycin and adverse cardiac outcomes. Treatment with macrolides is associated with an absolute risk increase of 118.1 additional SCDs or VTA, and 38.2 additional cardiovascular deaths per 1 million treatment courses.CONCLUSIONS Administration of macrolide antibiotics is associated with increased risk for SCD or VTA and cardiovascular death but not increased all-cause mortality. (C) 2015 by the American College of Cardiology Foundation.

This article introduces a mobile infrared silhouette imaging and sparse representation-based pose recognition for building an elderly-fall detection system. The proposed imaging paradigm exploits the novel use of the pyroelectric infrared (PIR) sensor in pursuit of body silhouette imaging. A mobile robot carrying a vertical column of multi-PIR detectors is organized for the silhouette acquisition. Then we express the fall detection problem in silhouette image-based pose recognition. For the pose recognition, we use a robust sparse representation-based method for fall detection. The normal and fall poses are sparsely represented in the basis space spanned by the combinations of a pose training template and an error template. The ℓ 1 norm minimizations with linear programming (LP) and orthogonal matching pursuit (OMP) are used for finding the sparsest solution, and the entity with the largest amplitude encodes the class of the testing sample. The application of the proposed sensing paradigm to fall detection is addressed in the context of three scenarios, including: ideal non-obstruction, simulated random pixel obstruction and simulated random block obstruction. Experimental studies are conducted to validate the effectiveness of the proposed method for nursing and homeland healthcare.

Fall is a common daily activity and a leading cause of death among the older adults. It reveals growing demands to use some non-invasive methods to detect the pose of older people and give a timely and efficient alert, especially in some place with high fall-risk. This article presents a radio tomographic imaging (RTI) based approach for fall detection. A wireless network organized by a group of radio-frequency sensors is used for human pose sensing in the vertical direction. The human body would cause the statistical shadowing losses on the passing links between pairs of nodes in the network. Then an attenuation image of body pose can be obtained by using the received signal strength measurements. The non-negative total variation minimization is used to reconstruct the gray image of body. The fall detection is cast as an image recognition problem. This is a new approach based on the use of RTI to enable the building of a fall detection system. Experimental studies are conducted to validate the proposed method.

Background: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL), is an aggressive type of lymphoma whose standard treatment and validated prognostic model have not yet been defined.Methods: CD30 expression was detected using immunohistochemistry in 96 ENKTL patients, and the data were used to evaluate its relationship with clinical features, treatment response and prognosis.Results: Expression of CD30 was detected in 31.2% of ENKTL patients, which was significantly correlated with B symptoms and elevated serum lactate dehydrogenase. The complete remission rate was not significantly different between CD30-positive and negative groups. After a median follow-up time of 31 months, 5-year overall survival (OS) and 5-year progression-free survival (PFS) rates in the CD30-positive group were both significantly lower than those in the CD30-negative group (34.1% vs. 64.4%, P = 0.002, for 5 year-OS; 26.0% vs. 66.7%, P < 0.001, for 5 year-PFS). In patients with an International Prognostic Index (IPI) or Korean Prognostic Index (KPI) score of 0-1, CD30 positivity was associated with shorter 5-year OS and PFS (IPI: P = 0.001 and 0.002, respectively; KPI: P = 0.018 and 0.023, respectively). In a multivariate Cox regression model, CD30 expression and stage were independent prognostic factors for OS (p = 0.004 and p = 0.012, respectively) and PFS (p = 0.001 and p = 0.022, respectively).Conclusions: Our results showed that expression of CD30 was not related to response to treatment but was an independent prognostic factor for both OS and PFS in ENKTL, nasal type, which suggests a role for CD30 in the pathogenesis of this disease and may support the incorporation of anti-CD30-targeted therapy into the treatment paradigm for ENKTL.

To report 10 rare cases of acute myocardial infarction complicated with acute pancreatitis. A chart review was conducted on patients diagnosed as both acute myocardial infarction and acute pancreatitis from 2003-2013 at the first affiliated hospital of Sun Yat-sen University. A cohort of these

Objective Rho-associated coiled-coil kinase 2 (ROCK2) is an attractive therapeutic target because it is overexpressed in many malignancies, including glioma. Therefore, we designed the current study to determine whether the downregulation of ROCK2 would sensitize the cytotoxic effect of temozolomide (TMZ) in U251 cells. Methods Glycol-polyethyleneimine (PEG-PEI) was used to deliver siROCK2 to U251 cells, and the physical characteristics of the PEG-PEI/siROCK2 complex (referred to as the siROCK2 complex) were investigated. The transfection efficiency and cell uptake were determined by flow cytometry (FCM) and confocal laser microscopy (CLSM), respectively. U251 cells were then treated with 100 μM TMZ, siROCK2 complexes or their combination. The apoptosis rate and cell migration were measured by FCM and wound-healing assay, respectively. The levels of Bax, Bcl-2, cleaved caspase-3, MMP-2, and MMP-9 were detected to analyze the degrees of apoptosis and migration. Results Our results revealed that the characteristics of the siROCK2 complexes depended closely on the N/P ratios. PEG-PEI served as a good vector for siROCK2 and exhibited low cytotoxicity toward U251 cells. The CLSM assay showed that the siROCK2 complexes were successfully uptaken and that both the protein and mRNA levels of ROCK2 were significantly suppressed. Furthermore, the combination treatment induced a higher apoptosis rate and markedly increased the gap distance of U251 cells in the wound-healing assay. Levels of the proapoptotic proteins Bax and cleaved caspase-3 were significantly increased, whereas levels of the antiapoptotic protein Bcl-2 and the migration-related proteins MMP-2 and MMP-9 were significantly reduced by the combination treatment compared with either treatment alone. Conclusions In conclusion, our results demonstrate that the combination of TMZ and siROCK2 effectively induces apoptosis and inhibits the migration of U251 cells. Therefore, the combination of TMZ and siROCK2 complex is a potential therapeutic approach for human glioma.

The TATA box represents one of the most prevalent core promoters where the pre-initiation complexes (PICs) for gene transcription are assembled. This assembly is crucial for transcription initiation and well regulated. Here we show that some cellular microRNAs (miRNAs) are associated with RNA polymerase II (Pol II) and TATA box-binding protein (TBP) in human peripheral blood mononuclear cells (PBMCs). Among them, let-7i sequence specifically binds to the TATA-box motif of interleukin-2 (IL-2) gene and elevates IL-2 mRNA and protein production in CD4(+) T-lymphocytes in vitro and in vivo. Through direct interaction with the TATA-box motif, let-7i facilitates the PIC assembly and transcription initiation of IL-2 promoter. Several other cellular miRNAs, such as mir-138, mir-92a or mir-181d, also enhance the promoter activities via binding to the TATA-box motifs of insulin, calcitonin or c-myc, respectively. In agreement with the finding that an HIV-1-encoded miRNA could enhance viral replication through targeting the viral promoter TATA-box motif, our data demonstrate that the interaction with core transcription machinery is a novel mechanism for miRNAs to regulate gene expression.