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Abstract Small extracellular vesicle–derived microRNAs (sEV-miRNAs) have emerged as promising noninvasive biomarkers for early cancer diagnosis. Herein, we developed a molecular probe based on three-dimensional (3D) multiarmed DNA tetrahedral jumpers (mDNA-Js)-assisted DNAzyme activated by Na+, combined with a disposable paper-based electrode modified with a Zr-MOF–rGO–Au NP nanocomplex (ZrGA) to fabricate a novel biosensor for sEV-miRNAs Assay. Zr-MOF tightly wrapped by rGO was prepared via a one-step method, and it effectively aids electron transfer and maximizes the effective reaction area. In addition, the mechanically rigid, and nanoscale-addressable mDNA-Js assembled from the bottom up ensure the distance and orientation between fixed biological probes as well as avoid probe entanglement, considerably improving the efficiency of molecular hybridization. The fabricated bioplatform achieved the sensitive detection of sEV-miR-21 with a detection limit of 34.6 aM and a dynamic range from100 aM to 0.2 µM. In clinical blood sample tests, the proposed bioplatform showed results highly consistent with those of qRT-PCRs and the signal increased proportionally with the NSCLC staging. The proposed biosensor with a portable wireless USB-type analyzer is promising for the fast, easy, low-cost, and highly sensitive detection of various nucleic acids and their mutation derivatives, making it ideal for POC biosensing.

IntroductionGlioblastoma, despite advancements in molecular evolution, remains incurable and has low survival rates. Currently, two of the most commonly used chemotherapy regimens are temozolomide and CCNU. This review aims to provide a comprehensive analysis of the current status of chemotherapy strategies for GBM.MethodsWe reviewed the published literature describing the chemotherapy regimen differences in system treatment of GBM reported in the last ten years and summarised the available information that may reveal the latest changes in chemotherapy.ResultsIn patients with adequate functioning, temozolomide and radiation are the primary treatments for newly diagnosed GBM. We recommend postoperative radiation therapy with concurrent and adjuvant temozolomide for patients with MGMT-methylated GBM who are less than 70 years old. Combining temozolomide and lomustine with radiation therapy may be an option for younger, fit patients, but efficacy data is inconclusive. For patients with unknown MGMT methylation status, radiation therapy combined with temozolomide remains the standard of care. We recommend hypofractionated radiation and concurrent temozolomide treatment for elderly patients over 70 years old who have satisfactory performance and no significant underlying health conditions. We should tailor treatment choices to each patient’s personal preferences, previous treatments, function, quality of life, and overall care objectives.ConclusionRadiation therapy, along with temozolomide, is still the standard of care for most people with MGMT-unmethylated GBMs because there aren’t any better options, and it’s generally safe and well-tolerated. These patients have a lower overall survival rate and less benefit from temozolomide, but there are no better alternatives. Clinical trial participation is encouraged.

The treatment of wound inflammation is intricately linked to the concentration of reactive oxygen species (ROS) in the wound microenvironment. Among these ROS, H2O2 serves as a critical signaling molecule and second messenger, necessitating the urgent need for its rapid real-time quantitative detection, as well as effective clearance, in the pursuit of effective wound inflammation treatment. Here, we exploited a sophisticated 3D Cu2-xSe/GO nanostructure-based nanonzymatic H2O2 electrochemical sensor, which is further decorated with evenly distributed Pt nanoparticles (Pt NPs) through electrodeposition. The obtained Cu2-xSe/GO@Pt/SPCE sensing electrode possesses a remarkable increase in specific surface derived from the three-dimensional surface constructed by GO nanosheets. Moreover, the localized surface plasma effect of the Cu2-xSe nanospheres enhances the separation of photogenerated electron-hole pairs between the interface of the Cu2-xSe NPs and the Pt NPs. This innovation enables near-infrared light-enhanced catalysis, significantly reducing the detection limit of the Cu2-xSe/GO@Pt/SPCE sensing electrode for H2O2 (from 1.45 μM to 0.53μM) under NIR light. Furthermore, this biosensor electrode enables in-situ real-time monitoring of H2O2 released by cells. The NIR-enhanced Cu2-xSe/GO@Pt/SPCE sensing electrode provide a simple-yet-effective method to achieve a detection of ROS (H2O2、-OH) with high sensitivity and efficiency. This innovation promises to revolutionize the field of wound inflammation treatment by providing clinicians with a powerful tool for accurate and rapid assessment of ROS levels, ultimately leading to improved patient outcomes.

Complementary multi-energy power generation systems are a promising solution for multi-energy integration and an essential tool for diversifying renewable energy sources. Despite many studies on developing hybrid renewable energy systems, more research is still needed on applicable models or practical methods. Meta-heuristic algorithms such as the Firefly algorithm are becoming increasingly popular in optimizing hybrid renewable energy systems because they provide fast, accurate, and optimal solutions. Considering the natural complementarity and instability of wind and solar energy, the advantage of pumped storage power plants’ “peak adjustment and valley adjustment”, as well as the grid’s need for a stable and reliable energy supply, the objective of this study is to economically optimize the design of wind-PV pumped storage complementary generation system scheduling with a two-generation Firefly algorithm based on spatial adaptive and Levy’s flight improvement, in comparison with a variety of cutting-edge population intelligence optimization algorithms (GA, PAO, DE, WOA, FA) were compared and analyzed. The impact of pumped storage plants on economic and stabilization objectives is explored. The results show that several meta-heuristics are effective in finding the optimal design. However, the improved Firefly algorithm with an objective function value of 7.8331 is superior to several other algorithms by enhancing the wind and PV benefits while suppressing the output fluctuations of the system. After the construction of the additional pumped storage plant, the output fluctuation of the complementary operation system is only 9.7% of that of the wind power and PV in stand-alone operation after the multi-energy coordination and optimal scheduling. This demonstrates the effectiveness of the optimization method used in this paper. The results of this study can provide a reference for the complementary optimization of pumped storage power plants for intermittent renewable energy sources.

Abstract Background Paclitaxel liposome (Lipusu) is known to be effective in non-small cell lung cancer (NSCLC) as first-line treatment. This study aimed to evaluate the effectiveness and safety of paclitaxel liposome based chemotherapy plus PD-1/PD-L1 inhibitor in patients with advanced NSCLC. Methods In this multicenter, retrospective, real-world study, patients with advanced NSCLC who were administered paclitaxel liposome based chemotherapy plus PD-1/PD-L1 inhibitor in three centers (Peking University People’s Hospital as the lead center) in China between 2016 and 2022 were included. Progression-free survival (PFS), overall survival (OS), objective response rate, disease control rate, and adverse events (AEs) were evaluated. Results A total of 49 patients were included, with 33 (67.3%) receiving paclitaxel liposome based chemotherapy plus PD-1/PD-L1 inhibitor as first-line treatment. There were 34 patients (69.4%) diagnosed with squamous cell carcinoma and 15 (30.6%) with adenocarcinoma. The median follow-up was 20.5 (range: 3.1–41.1) months. The median PFS and OS of all patients were 9.7 months (95% confidence interval [CI], 7.0-12.4) and 30.5 months (95% CI, not evaluable-not evaluable), respectively. Patients with squamous cell carcinoma and adenocarcinoma had median PFS of 11 months (95%CI, 6.5–15.5) and 9.3 months (95%CI, 7.0-12.4), respectively. The median PFS was 9.9 months (95%CI, 7.1–12.7) in patients who received the combined regimen as first-line treatment. Treatment-related AEs of any grade were observed in 25 (51.0%) patients, and AEs of grade 3 or worse were observed in nine patients (18.4%). The most common treatment-related AEs were myelosuppression (14.3%) and fever (10.2%). Conclusions Paclitaxel liposome based chemotherapy plus PD-1/PD-L1 inhibitor prolonged the PFS in advanced NSCLC with acceptable safety, which was worthy of clinical application.

Since its initial release in 2001, the human reference genome has undergone continuous improvement in quality, and the recently released telomere-to-telomere (T2T) version — T2T-CHM13 — reaches its highest level of continuity and accuracy after 20 years of effort by working on a simplified, nearly homozygous genome of a hydatidiform mole cell line. Here, to provide an authentic complete diploid human genome reference for the Han Chinese, the largest population in the world, we assembled the genome of a male Han Chinese individual, T2T-YAO, which includes T2T assemblies of all the 22 + X + M and 22 + Y chromosomes in both haploids. The quality of T2T-YAO is much better than those of all currently available diploid assemblies, and its haploid version, T2T-YAO-hp, generated by selecting the better assembly for each autosome, reaches the top quality of fewer than one error per 29.5 Mb, even higher than that of T2T-CHM13. Derived from an individual living in the aboriginal region of the Han population, T2T-YAO shows clear ancestry and potential genetic continuity from the ancient ancestors. Each haplotype of T2T-YAO possesses ∼ 330-Mb exclusive sequences, ∼ 3100 unique genes, and tens of thousands of nucleotide and structural variations as compared with CHM13, highlighting the necessity of a population-stratified reference genome. The construction of T2T-YAO, an accurate and authentic representative of the Chinese population, would enable precise delineation of genomic variations and advance our understandings in the hereditability of diseases and phenotypes, especially within the context of the unique variations of the Chinese population.

In this paper, two flower-like magnesium silicate nanomaterials were prepared. These and another two commercial magnesium silicate materials were characterized using a scanning electron microscope, the N2 adsorption–desorption method, and other methods. The structure–activity relationship between the adsorption performance of these four magnesium silicate materials and their specific surface area, pore size distribution, and pore structure was compared. The results showed that the 3-FMS modified by sodium dodecyl sulfonate (SDS) had the largest specific surface area and pore size, the best adsorption performance, and the largest experimental equilibrium adsorption capacity (qe,exp) for Co2+, reaching 190.01 mg/g, and Cr3+, reaching 208.89 mg/g. The adsorption behavior of the four materials for Co2+ and Cr3+ both fitted the pseudo-second-order kinetic model and Langmuir adsorption model, indicating that chemical monolayer uniform adsorption was the dominant adsorption process. Among them, the theoretical adsorption capacity (qm) of 3-FMS was the highest, reaching 207.62 mg/g for Co2+ and 230.85 mg/g for Cr3+. Through further research, it was found that the four materials mainly removed Co2+ and Cr3+ through electrostatic adsorption, surface metal ions (Mg2+), and acidic groups (-OH and -SO3H) exchanging with ions in solution. The adsorption performance of two self-made flower-like magnesium silicate materials for Co2+ and Cr3+ was superior to that of two commercial magnesium silicates.

Upper limb exoskeleton is gradually used in industrial production because of its flexibility, safety, and ease of wear. To improve the load reduction effect of the upper limb exoskeleton in power grid operation, this paper first establishes an efficiency optimization model considering the number of gears, transmission ratio, and pressure angle of upper limb exoskeleton transmission joint gears. Further, an exoskeleton load reduction model based on the joint optimization of multiple parameters of the upper limb exoskeleton is constructed by combining the muscle force application fatigue evaluation. For the above model, a hybrid simulated annealing-flash connection process algorithm based on Cubic mapping and golden sine is designed for the solution. To address the shortcomings of the standard LAPO, Cubic mapping, simulated annealing algorithm, and golden sine operator are introduced for improvement, producing high-quality initial solutions through the traversal of Cubic chaotic sequences, hybrid simulated annealing algorithm to enhance the global search capability of the algorithm, and further incorporating golden sine operator to strengthen the local search capability of the algorithm. In the simulation section, the designed Improved Lightning Connection Process Algorithm (ILAPO) is compared horizontally with cutting-edge swarm intelligence algorithms such as LAPO, PSO, and HBA to verify the feasibility of the model in this paper in the exoskeleton domain and the efficiency of the designed algorithm.

Coronavirus disease 2019 (COVID-19) has caused more than 500 million infections and 6.2 million deaths globally, resulting in numerous sporting events being cancelled or postponed. Therefore, effective control strategies are urgently needed to prevent COVID-19 transmission at these local and global events. This article introduced the strategies utilized at the Tokyo and Beijing Olympics and proposed several measures for future reference.

Abstract With the continuous increase in social pressure and people’s higher urgency for physical health, the concept of healthy physical fitness has become more and more important and prominent. However, the research and standards for the validity of the health fitness monitoring test indicators have not been determined. In order to compare the validity of the health fitness test indicators, we adopt the cardiopulmonary track and field sensor technology to monitor the health fitness cardiopulmonary track and field sensor. A comparative study on the validity of test indicators, mainly to test the rationality of the cardiopulmonary endurance evaluation indicators of healthy physical fitness, and to carry out a new design of the concept of healthy physical fitness in track and field teaching, so that it is more inclined to improve the healthy physical fitness of athletes fitness. Research data shows that the average absolute value of the athlete’s maximum oxygen consumption is 2.51 L/min, the highest value is 3.96 L/min, and the lowest is 2.03 L/min. The average value of the absolute maximum oxygen consumption of girls is 1.79 L/min, the highest value is 2.89 L/min, and the minimum is 1.51 L/min. From these data, we can know that compared with traditional cardiopulmonary monitoring methods, the sensor monitoring studied in this paper has higher accuracy and wider application range. The peak cardiopulmonary power of athletes’ cardiopulmonary function detection using this method is closer to the actual value, while for the peak cardiopulmonary power detected by traditional methods, there is a big difference between the power and the actual value. For different athletes, the advantages of the algorithm in this paper are more obvious, indicating that the method in this paper has a higher detection accuracy for the cardiopulmonary function test of athletes during aerobic training.

Community-acquired pneumonia (CAP) is a lower respiratory tract infection. It is one of the commonest infectious diseases and the third leading cause of death worldwide. However, the epidemiological profiles of CAP in southeastern China are unknown. Data of inpatients and outpatients diagnosed with CAP from January 1, 2015 to December 31, 2020 were obtained from the National Healthcare Big Data in Fuzhou (Fuzhou Database). This database covers medical data from 37 hospitals and 159 community health service stations. The incidence rate, treatment pattern, and direct medical costs of CAP were assessed using clinical data. A total of 8,156,237 patients were enrolled, with a mean age of 33.72 ± 20.88 years. The overall incidence rate of CAP was 3.13 (95% confidence interval [CI]: 3.11–3.15) per 1000 person-years (PY), with 15.97 (95% CI: 15.85–16.08) per 1000 PY in children below 5 years old and 2.62 (95% CI: 2.57–2.66) per 1000 PY in the elderly ≥60 years. The cost per outpatient was $242.83 ± 341.62, and the cost per inpatient was $4,530.4 ± 9,151.68. The three most used therapeutic drugs in patients with CAP are cefotaxime, moxifloxacin, and azithromycin. In addition, despite the ability of both imported and domestic pneumococcal conjugate vaccines to reduce the incidence rate of CAP, the current vaccination coverage rates were relatively low. We suggest that more attention should be paid to the disease burden of CAP, especially due to its great economic burden in China.

IntroductionPrevious studies have observed the association between caffeine intake and depression, but few have considered the potential threshold effect of this issue. Therefore, the study aimed to examine the association between caffeine consumption and depression in patients aged 20 years or older using curve fitting analysis.MethodsThe population was 3,263 patients from the 2017 to 2018 National Health and Nutrition Examination Survey (NHANES) with reliable answers to questions of caffeine intake and depression. Participants’ depression levels were assessed using the 9-item Patient Health Questionnaire (PHQ-9) depression scale and the caffeine consumption were investigated in a private room of NHANES. The confounding variables of this study included level of education, monthly sleepiness, age, marital status, race, cigarette smoking, sex and recreational activities.ResultsIn linear regression analysis, patients with a higher PHQ-9 score tend to have less caffeine intake. A similar conclusion was drawn in logistic regression model using PHQ-9 ≥ 10 as a cut-off score for depression. But when caffeine intake exceeded 90 mg, there was no significant association between caffeine intake and depression based on the curve fitting analysis.DiscussionThese results suggest that people can consume some caffeine to reduce depression. But further study is needed to examine the precise causal relationship between these factors.

Hypoxic environments are known to trigger pathological damage in multiple cellular subtypes. Interestingly, the lens is a naturally hypoxic tissue, with glycolysis serving as its main source of energy. Hypoxia is essential for maintaining the long-term transparency of the lens in addition to avoiding nuclear cataracts. Herein, we explore the complex mechanisms by which lens epithelial cells adapt to hypoxic conditions while maintaining their normal growth and metabolic activity. Our data show that the glycolysis pathway is significantly upregulated during human lens epithelial (HLE) cells exposure to hypoxia. The inhibition of glycolysis under hypoxic conditions incited endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) production in HLE cells, leading to cellular apoptosis. After ATP was replenished, the damage to the cells was not completely recovered, and ER stress, ROS production, and cell apoptosis still occurred. These results suggest that glycolysis not only performs energy metabolism in the process of HLE cells adapting to hypoxia, but also helps them continuously resist cell apoptosis caused by ER stress and ROS production. Furthermore, our proteomic atlas provides possible rescue mechanisms for cellular damage caused by hypoxia.

The practice of green consumption has become a common initiative of the international community. Existing studies have shown that emotional factors have an important impact on consumer behavior, but few scholars in the field of green consumption behavior have explored the relationship between positive emotions and green purchase behavior in specific dimensions. This study creatively put forward two dimensions and four kinds of positive emotional appeals which include the cherishing appeal, the yearning appeal, the proud appeal, and the admiring appeal. Through the conceptual model analysis based on the data, the effects of different four positive emotional appeals on consumers’ perceived green value, perceived green responsibility, and green purchase behaviors were confirmed. The results indicated that the four kinds of positive emotional appeals, perceived green value, perceived green responsibility, and green purchase behavior were positively correlated. Perceived green responsibility and perceived green value have significant mediating effect on the relationship between positive emotional appeals and green purchase behaviors. Middle doctrine significantly moderates the relationship between positive emotional appeals (Cherishing VS. Yearning) and perceived green value.

The synchronous detection and regulation of microRNAs (miRNAs) are essential for the early tumor diagnosis and treatment but remains a challenge. An integrative DNA tetrahedral nanomachine was self-assembled for sensitive detection and negative feedback regulation of intracellular miRNAs. This nanomachine comprised a DNA tetrahedron nanostructure as the framework, and a miRNA inhibitor-controlled allosteric DNAzyme as the core. The DNA tetrahedron brought the DNAzyme and the substrate in spatial proximity and facilitated the cellular uptake of DNAzyme. In allosteric regulation of DNAzyme, the locked tetrahedral DNAzyme (L-tetra-D) and active tetrahedral DNAzyme (A-Tetra-D) were controlled by miRNA inhibitor. The combination of miRNA inhibitor and target could trigger the conformational change from L-tetra-D to A-Tetra-D. A-Tetra-D cleaved the substrate and released fluorescence for intracellular miRNA biosensing. The DNA tetrahedral nanomachine showed excellent sensitivity (with detection limit down to 0.77 pM), specificity (with one-base mismatch discrimination), biocompatibility and stability. Simultaneously, miRNA stimulus-unlocked inhibitor introduced by our nanomachine exhibited the synchronous regulation of target cells, of which regulatory performance has been verified by the upregulated levels of downstream genes/proteins and the increased cellular apoptosis. Our study demonstrated that the DNA tetrahedral nanomachine is a promising biosense-and-treat tool for the synchronous detection and regulation of intracellular miRNA, and is expected to be applied in the early diagnosis and tailored management of cancers.

Objective: This review investigates the role of adjuvant therapy (AT) and the importance of histopathological typing in periampullary carcinoma (PAC) treatment. Background: PAC is a relatively rare gastrointestinal malignancy. The regimen and effect of AT in PAC are still controversial. However, there is a treatment based on histopathological types (pancreaticobiliary-type, PB-type or intestinal-type, IN-type), but there are no clear guidelines indicating that typing can be used to guide the selection of AT drugs. Methods: A literature search of PubMed and Web of Science databases was conducted for studies published from January 2001 to August 2021 on the use of AT in PAC. Results: A total of 75 studies were included in this review. According to existing studies, AT for PAC is mostly based on 5-FU or gemcitabine, but the effect is unknown. However, when PAC is classified into different histopathological types, AT with gemcitabine is beneficial for patients with the PB-type of PAC, while 5-FU-based AT is beneficial for patients with the IN-type of PAC. In addition, the benefits of AT are more pronounced in patients with a high-risk disease, such as patients with stage II/III, T3/T4 tumors, or positive lymph node involvement. There are few studies on targeted therapy and immunotherapy for PAC. Conclusions: This review suggests that AT has potential survival benefits, especially when based on the histopathologic type that helps the choice of drugs during AT in PAC patients.

Abstract. Background:. Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. In this study, we aimed to identify the risk factors for severe COVID-19 to improve treatment guidelines. Methods:. A multicenter, cross-sectional study was conducted on 313 patients hospitalized with COVID-19. Patients were classified into two groups based on disease severity (nonsevere and severe) according to initial clinical presentation. Laboratory test results and epidemiological and clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression models were used to detect potential risk factors associated with severe COVID-19. Results:. A total of 289 patients (197 nonsevere and 92 severe cases) with a median age of 45.0 (33.0, 61.0) years were included in this study, and 53.3% (154/289) were male. Fever (192/286, 67.1%) and cough (170/289, 58.8%) were commonly observed, followed by sore throat (49/289, 17.0%). Multivariate logistic regression analysis suggested that patients who were aged ≥ 65 years (OR: 2.725, 95% confidence interval [CI]: 1.317–5.636; P = 0.007), were male (OR: 1.878, 95% CI: 1.002–3.520, P = 0.049), had comorbid diabetes (OR: 3.314, 95% CI: 1.126–9.758, P = 0.030), cough (OR: 3.427, 95% CI: 1.752–6.706, P

Abstract An outbreak of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that started in Wuhan, China, at the end of 2019 has become a global pandemic. Both SARS-CoV-2 and SARS-CoV enter host cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed in various human organs. We have reviewed previously published studies on SARS and recent studies on SARS-CoV-2 infection, named coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO), confirming that many other organs besides the lungs are vulnerable to the virus. ACE2 catalyzes angiotensin II conversion to angiotensin-(1–7), and the ACE2/angiotensin-(1–7)/MAS axis counteracts the negative effects of the renin-angiotensin system (RAS), which plays important roles in maintaining the physiological and pathophysiological balance of the body. In addition to the direct viral effects and inflammatory and immune factors associated with COVID-19 pathogenesis, ACE2 downregulation and the imbalance between the RAS and ACE2/angiotensin-(1–7)/MAS after infection may also contribute to multiple organ injury in COVID-19. The SARS-CoV-2 spike glycoprotein, which binds to ACE2, is a potential target for developing specific drugs, antibodies, and vaccines. Restoring the balance between the RAS and ACE2/angiotensin-(1–7)/MAS may help attenuate organ injuries. Graphical abstract SARS-CoV-2 enters lung cells via the ACE2 receptor. The cell-free and macrophage-phagocytosed virus can spread to other organs and infect ACE2-expressing cells at local sites, causing multi-organ injury.

Abstract Background With the second largest tuberculosis (TB) burden globally, China is committed to actively engage in international TB clinical trials to contribute to global TB research. However, lack of research capacity among local sites has been identified as a barrier. Main text The China Tuberculosis Clinical Trials Consortium (CTCTC) was initiated by Beijing Chest Hospital with investment from the US National Institutes of Health and technical support from Family Health International 360 in 2013, as a nationwide collaborative clinical trial network to strengthen selected clinical site research capacity and attract TB clinical trials. The program aims to: 1) recruit leading hospitals that care for TB patients; 2) conduct on-site assessment to identify capacity gaps and needs for improvement; 3) design and deliver capacity building activities; 4) attract and deliver high quality results for TB clinical trials. A total of 24 sites have joined CTCTC, covering 20 provinces in China. Twenty-two sites have been accredited by the National Medical Products Administration (NMPA) to be qualified to conduct TB clinical trials. The onsite assessment, extensive trainings among the CTCTC sites and young investigators have resulted in better understanding and improvement of the site capacity in conducting TB clinical trials. The establishment and growth of the CTCTC network has benefited from the good leadership, effective international cooperation and local commitment. Issues in human resources, regulatory environment and sustainability have been challenging the network from continuing growth. Clinical researchers have full-time clinical responsibilities in China and it is thus important to build a cadre of other human resources to assist. The regulatory environment is becoming friendlier in China to introduce international clinical trials to the CTCTC network. Conclusions The CTCTC, with mature management structure and sustainable development model, which are distilled five key lessons for other developing countries or investigators of interest. They are the respectively using assessment-based approach to design tailored training package, understanding the availability of clinical researchers, providing solutions to maintain sustainability, understanding local regulatory environments and working with an international organization with local on-site team, respectively. Although, the experiences and capacity of China’s TB hospitals in conducting clinical research vary. Considerable efforts to continue building the capacity are still needed, although the gap is smaller for a few top-tier hospitals.

Introduction. Mucormycosis is a rare, invasive disease caused by opportunistic pathogens related to the Mucorales order with high fatality rates in immunocompromised hosts, especially in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Diagnosis and treatment of pulmonary mucormycosis in recipients of allo-HSCT remains challenging. Purpose. The aim of this study is to summarize and analyze the clinical features of pulmonary mucormycosis in recipients of allo-HSCT to explore further clinical research directions for this rare fungal infection in the particular populations. Methods. We retrospectively reviewed pulmonary mucormycosis in patients who received allo-HSCT in our hospital from January 2010 to December 2020. A total of 21 patients fulfilled the diagnostic criteria for pulmonary mucormycosis according to the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) criteria. Demographic and clinical data, mycological and histopathological records, and treatment and prognosis data were collected. Clinical variables were compared between survivors and nonsurvivors. The survival days of patients with and without graft-versus-host disease (GVHD) and hemoptysis were compared separately. Results. Most of the recipients of allo-HSCT were male patients with a mean age of 43 years. Acute myeloid leukemia (AML) was the most common primary hematologic malignancy. Extrapulmonary involvement accounted for 28.6%, of the cases, including central nervous system (n = 5) and skin and soft tissue (n = 1). The median time to infection was 96 days after allo-HSCT. Clinical presentations were nonspecific, including fever (76.2%) and cough (85.7%), as well as dyspnea (19.0%), chest pain (38.1%), and hemoptysis (61.9%). Ground-glass infiltrates (95.0%) and nodules/masses (80%) were the most common radiographic patterns on chest CT. The most common pathogen was Rhizopus (63.2%), and breakthrough infection accounted for 90.5%. Fifteen of the patients died within one year, and the median time from diagnosis to death was 47 days. Conclusion. Mucormycosis is a fatal infection disease. Opportunistic infections in recipients of allo-HSCT are mainly breakthrough infections and may have a seasonal distribution (summer and autumn) and more cases of death in autumn. The marked reversed halo sign can be seen both in the initial stage of infection and after antifungal treatment. In our case series, patients with pulmonary mucormycosis with extrapulmonary involvement 100% died within one year. There are more patients with GVHD before infection and hemoptysis in nonsurvivors than survivors within 100 days. Patients with GVHD before infection and hemoptysis have a shorter survival time than those without.

Background. Ulcerative colitis (UC) is characterized by chronic, recurrent intestinal inflammation and intestinal epithelial injury including a wide range of epithelial cell death, ulcers, crypt abscesses, and the formation of fibrosis. The intestinal barrier dysfunction runs through the whole process of the occurrence and development of UC. A recent study revealed that an ubiquitin binding protein ABIN1 played a role in tissue homeostasis and autoimmunity diseases which involved in the anti-inflammatory response of intestinal epithelia cells. However, the roles of ABIN1 in ulcerative colitis pathogenesis remain unclear. Methods. The mRNA and protein expression level of ABIN1 and necroptosis-associated genes (RIPK1, RIPK3, and MLKL) were conducted to investigate the relationship between ABIN1 and necroptosis in clinical UC specimens. Subsequently, the dextran sodium sulfate (DSS)-induced mice colitis model was used to verify the ABIN1 function in vivo. Furthermore, we established ABIN1 gain and loss function assay in CACO-2 to confirm the mechanism in UC in vitro. Results. We found that ABIN1, RIPK1, RIPK3, and MLKL were upregulated in UC sample and DSS-induced colitis. Upon TNF-α stimulation in the intestinal epithelia cell line, overexpression of ABIN1 significantly inhibits necroptosis in the intestinal inflammation model along with the reduction expression of pro-inflammatory cytokines such as IL1B, IL6, IL8, and TNF-α. Blocking RIPK1 by Nec-1s in vivo and in vitro dramatically alleviated the colitis and cell death which shares the same phenotype with ABIN1 overexpression. Conclusion. Hence, the dysregulation of ABIN1 may relate to the uncontrolled necroptosis and inflammation in UC, and negatively regulate the occurrence and process of ulcerative colitis. ABIN1 activation may be considered a therapeutic strategy for UC.

To solve the decision problem of train stopping schemes, this paper introduces the static game into the optimal configuration of stopping time to realize the rational decision of train operation. First, a train energy consumption model is constructed with the lowest energy consumption of train operation as the optimization objective. In addition, a Mustang optimization algorithm based on cubic chaos mapping, the population hierarchy mechanism, the golden sine strategy, and the Levy flight strategy was designed for solving the problem of it being easy for the traditional population intelligence algorithm to fall into a local optimum when solving complex problems. Lastly, simulation experiments were conducted to compare the designed algorithm with PSO, GA, WOA, GWO, and other cutting-edge optimization algorithms in cross-sectional simulations, and the results show that the algorithm had excellent global optimization finding and convergence capabilities. The simulation results show that the research in this paper can provide effective decisions for the dwell time of trains at multiple stations, and promote the intelligent operation of the train system.

Rheumatoid arthritis (RA) is characterized by tumor-like expansion of the synovium and the subsequent destruction of adjacent articular cartilage and bone. The latest studies proved phosphatase and tension homolog deleted on chromosome 10 (PTEN) might contribute to the surviving, proliferation and pro-inflammatory cytokines in RA. The purpose of this study was to explore the function and underlying mechanisms of PTEN in RA pro-inflammatory cytokines and chemokines of fibroblast-like synoviocytes (FLSs). Increased level of PTEN was observed in adjuvant-induced arthritis (AIA) FLSs in comparison to normal rats. Increased concentrations of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), chemokines (CCL-2 and CCL-3), VCAM-1 and VEGF-α expression were observed in FLSs with PTEN inhibitor bpv or PTEN-RNAi. Moreover, co-incubation FLSs with overexpression vector with PTEN-GV141 reduced the expression of pro-inflammatory cytokines, chemokines, VCAM-1 and VEGF-α in AIA. Interestingly, we also found DNA methylation could regulate PTEN expression and activation of AKT signaling was with a change of PTEN. Altogether, our findings in the present study suggested that PTEN might play a pivotal role during pro-inflammatory cytokines and chemokines of FLSs through activation of AKT signaling pathway. In addition, PTEN expression may be regulated by DNA methylation in the pathogenesis of AIA.

As one of the most important water conservancy projects, reservoirs use water resources to achieve essential functions, such as irrigation, flood control, and power generation, by intercepting rivers. As climate extremes and global warming increase, the world’s water reserves are being tested, and reservoir operators are being challenged. This paper investigates the optimal allocation of shared resources for hydropower to achieve rational decisions for reservoir operations. Firstly, a power resource model is constructed based on the real hydroelectric generator theory. Furthermore, based on the established power resource model combined with the influence of weather type and multi-region heterogeneous demand, this paper constructs a multi-objective hydropower shared resource allocation optimization model, with the lowest hydropower resource supply cost and the shortest time hydropower resource supply time as the optimization objectives. Secondly, for the problem that the traditional population intelligence algorithm easily falls into the local optimum when solving complex problems, the improvement of the MOPSO algorithm is completed by introducing the Levy flight strategy and differential evolution. Finally, simulation experiments were carried out, and cutting-edge algorithms, such as the GA algorithm and WOA algorithm, were selected for simulation comparison to verify the effectiveness of the constructed model and algorithm. The simulation results show that the research in this paper can contribute to effective decision-making for reservoir operators and promote intelligent reservoir operation.

Epstein-Barr virus (EBV)-associated lymph nodal T/NK cell lymphoma (nodal TNKL) is a rare and aggressive malignancy with an extremely poor prognosis. Although treatments of extranodal NK/T cell lymphoma are frequently reported, the characteristics and pathogenesis of EBV-associated nodal TNKL are different. However, there is no known effective therapy regimen at present. Here, we reported the clinical efficacy and feasibility of the programmed death 1 (PD-1) blockade therapy regimen in an elderly female patient with EBV-associated nodal TNKL. The patient failed to respond to cyclophosphamide, doxorubicin, vindesine, and prednisone regimen but achieved complete response after three cycles of anti-PD-1 antibody (tislelizumab) combined with gemcitabine and oxaliplatin (GemOx) regimen. The finding indicated that tislelizumab combined with the GemOx regimen may be a potent salvage regimen for EBV-associated nodal TNKL.

Glioma is a primary brain cancer with high malignancy and morbidity. Current management for glioma cannot reach optimal remission. Therefore, it is necessary to find novel targets for glioma treatment. Ubiquitin-conjugating enzyme E2 D3 (UBE2D3) is involved in the pathogenesis of various kinds of cancer. However, its role in glioma remains unclear. Our study aims to explore the function and underlying mechanism of UBE2D3 in the development of glioma. By analysis with The Cancer Genome Atlas-Glioblastoma multiforme (TCGA-GBM) dataset, we found that UBE2D3 was highly expressed in glioma and it is positive correlation with glycolysis, apoptosis, and STAT3 pathway. Then, we explore the effects of UBE2D3 knockdown in the biological functions of glioma cell lines. Cell proliferation and apoptosis were estimated by cell counting kit-8 assay and flow cytometry. Extracellular acidification rate and oxygen consumption rate were estimated to determine the level of cell glycolysis. Xenograft experiments were performed to identify in vivo function of UBE2D3. The results showed that the inhibition of UBE2D3 could suppress the proliferation, glycolysis, and STAT3 phosphorylation of GBM both in vitro and in vivo. UBE2D3 could interact with SHP-2 and promoted its ubiquitination, which elevated the activation of STAT3 pathway. Overexpressed SHP-2 could reverse the effect of UBE2D3 and they shared contrary expression patterns in glioma and normal brain tissues. In summary, our study revealed that UBE2D3 could promote the ubiquitination of SHP-2, which activated STAT3 pathway and promoted glioma proliferation as well as glycolysis. UBE2D3 could be a potential target for glioma treatment.

Abstract Background Hand, foot and mouth disease (HFMD) is a rising public health problem and has attracted considerable attention worldwide. The purpose of this study was to develop an optimal model with meteorological factors to predict the epidemic of HFMD. Methods Two types of methods, back propagation neural networks (BP) and auto-regressive integrated moving average (ARIMA), were employed to develop forecasting models, based on the monthly HFMD incidences and meteorological factors during 2009–2016 in Jiangsu province, China. Root mean square error (RMSE) and mean absolute percentage error (MAPE) were employed to select model and evaluate the performance of the models. Results Four models were constructed. The multivariate BP model was constructed using the HFMD incidences lagged from 1 to 4 months, mean temperature, rainfall and their one order lagged terms as inputs. The other BP model was fitted just using the lagged HFMD incidences as inputs. The univariate ARIMA model was specified as ARIMA (1,0,1)(1,1,0)12 (AIC = 1132.12, BIC = 1440.43). And the multivariate ARIMAX with one order lagged temperature as external predictor was fitted based on this ARIMA model (AIC = 1132.37, BIC = 1142.76). The multivariate BP model performed the best in both model fitting stage and prospective forecasting stage, with a MAPE no more than 20%. The performance of the multivariate ARIMAX model was similar to that of the univariate ARIMA model. Both performed much worse than the two BP models, with a high MAPE near to 40%. Conclusion The multivariate BP model effectively integrated the autocorrelation of the HFMD incidence series. Meanwhile, it also comprehensively combined the climatic variables and their hysteresis effects. The introduction of the climate terms significantly improved the prediction accuracy of the BP model. This model could be an ideal method to predict the epidemic level of HFMD, which is of great importance for the public health authorities.

Background: Ozone (O3) exposure elicits allergic rhinitis (AR) exacerbations by mechanisms that remain poorly understood. We used a rat model to investigate the effects of O3 on eosinophilic airway inflammation and Th2-related response. Methods: Sprague-Dawley (SD) rats were sensitized and challenged with ovalbumin (OVA) to make AR models. Three groups of AR rats were exposed respectively to 0.5, 1.0, 2.0 ppm of O3 for 2 h daily over 6 weeks consecutively and studied 24 h later. Normal rats exposed to O3 alone were used as controls. Nasal symptoms and OVA-specific immunoglobulin E (OVA-sIg E) in the serum were evaluated. Inflammatory cells in nasal lavage fluid (NLF) were classified and counted. Cytokines protein levels in NLF were assessed by ELISA. The pathological changes in the nasal mucosa were examined by histology. Results: The combination of allergen and repeated O3 exposure in rats induced a significant increase of the number of sneezes, nasal rubs, amount of nasal secretion and OVA-sIgE in the serum, accompanied by enhancement of eosinophils in NLF and nasal mucosa. The increase of interleukin-5 (IL-5), IL-13, Eotaxin and decrease of INF-γ protein levels in NLF were detected in AR rats after O3 inhalation. Hematoxylin and eosin staining showed disordered arrangement of the nasal mucosa epithelium and eosinophilic infiltration in a concentration-dependent manner. Conclusions: O3 inhalation deteriorated symptoms in AR rats, and the possible mechanism is that ozone co-exposure could enhance the expression of Th2 cytokines, eosinophilic airway inflammation dose-dependently. The observation is helpful for us to understand the synergistic effect of O3 in the air pollution and allergen on aggravating allergic rhinitis.

Community-acquired pneumonia (CAP) is a respiratory disease frequently requiring hospital admission, and a significant cause of death worldwide. This study aimed to investigate the prognostic value of clinical indicators. A prospective, multi-center study was conducted (January 2017-December 2018) where patient demographic and clinical data were recorded (N = 366). The 30-day mortality rate was 5.46%. Cox Regression analyses showed that serum albumin (ALB) and respiratory rate (RR) were independent prognostic variables for 30-day survival in patients with CAP. Albumin negatively correlated with the Pneumonia Severity Index (PSI) and CURB-65 scores using Pearson and Spearman tests. Survival curves showed that a RR >24 breaths/min or ALB ≤30 g/L were associated with a significantly higher risk of mortality. The area-under-the-curve (AUC) for predicting 30-day mortality in patients with CAP was 0.762, 0.763, 0.790, and 0.784 for ALB, RR, PSI, and CURB-65, respectively. The AUC for the prediction of 30-day mortality using ALB combined with PSI, CURB-65 scores, and RR was 0.822 (95% CI 0.731-0.912), 0.847 (95% CI 0.755-0.938), and 0.847 (95% CI 0.738-0.955), respectively. Albumin and RR were found to be reliable prognostic factors for CAP. This combination showed equal predictive value when compared to adding ALB assessment to PSI and CURB-65 scores, which could improve their prognostic accuracy.

Low molecular weight fucoidan (LMWF) has been reported to have immunomodulation effects through the increase of the activation and function of macrophages. In this study, the regulating effect of LMWF from Undaria pinnatifida grown in New Zealand on dendritic cells (DCs) was investigated. We discovered that LMWF could stimulate DCs’ maturation and migration, as well as CD4+ and CD8+ T cells’ proliferation in vitro. We proved that this immune promoting activity is activated through TLR4 and its downstream MAPK and NF–κB signaling pathways. Further in vivo (mouse model) investigation showed that LMWF has a strong immunological boosting effect, such as facilitating the proliferation of immune cells and increasing the index of immune organs. These findings suggest that LMWF has a positive immunomodulatory effect and is a promising candidate to supplement cancer immunotherapy.

The purpose of the current study was to investigate how the potential multifactors influence mothers’ emotion socialization. This study involved 300 Japanese-speaking married mothers with 2–5-year-old children, who answered a series of measures of emotion socialization (coaching, dismissing, dysfunction, and non-involvement), emotion regulation strategy (reappraisal and expressive suppression), psychopathology (anxiety and depression), and perceived parenting alliance with their partners. (a) Hierarchical multiple regression analyses demonstrated different effects between maternal anxiety and depression, such that higher levels of depression were associated with less coaching and higher levels of anxiety were associated with more dismissing and dysfunction. (b) Moreover, maternal emotion regulation was significant even when controlling for psychopathology, in which reappraisal had significant positive association with coaching and, conversely, expressive suppression had significant negative association with coaching and positive associations with non-involvement, dismissing, and dysfunction. (c) Additionally, moderation analysis revealed that a greater use of reappraisal was associated with more coaching, and this relation was strongest in lower levels of parenting alliance. Similarly, a greater use of reappraisal was associated with less dysfunction only when parenting alliance was low. Reappraisal may be effective in promoting supportive emotion socialization and buffering the negative effect of lower parenting alliance on unsupportive emotion socialization. Based on Belsky’s process of parenting model, we incorporate maternal psychopathology, emotion regulation, and perceived parenting alliance into one model of influencing maternal emotion socialization and highlight the unique role of emotion regulation.

MicroRNA-141-5p (miR-141-5p), an important member of the miR-200 family, has been reported to be involved in cellular proliferation, migration, invasion, and drug resistance in different kinds of human malignant tumors. However, the role and function of miR-141-5p in chronic myeloid leukemia (CML) are unclear. In this current study, we found that the level of miR-141-5p was significantly decreased in peripheral blood cells from CML patients compared with normal blood cells and human leukemic cell line (K562 cells) compared with normal CD34+ cells, but was remarkably elevated in patients after treatment with nilotinib or imatinib. Suppression of miR-141-5p promoted K562 cell proliferation and migration in vitro. As expected, overexpression of miR-141-5p weakened K562 cell proliferation, migration, and promoted cell apoptosis. A xenograft model in nude mice showed that overexpression of miR-141-5p markedly suppressed tumor growth in vivo. Mechanistic studies suggested that RAB32 was the potential target of miR-141-5p, and silencing of RAB32 suppressed the proliferation and migration of K562 cells and promoted cell apoptosis. Taken together, our study demonstrates that miR-141-5p plays an important role in the activation of K562 cells in vitro and may act as a tumor suppressor via targeting RAB32 in the development of CML.

Abstract Both PET/CT and breast MRI are used to assess pathological complete response to neoadjuvant chemotherapy (NAC) in patients with breast cancer. The aim is to compare the utility of PET/CT and breast MRI by using head-to-head comparative studies. Literature databases were searched prior to July 2016. Eleven studies with a total of 527 patients were included. For PET/CT, the pooled SEN was 0.87 (95% confidence interval (CI): 0.71–0.95) and SPE was 0.85 (95% CI: 0.70–0.93). For MRI, the pooled SEN was 0.79 (95% CI: 0.68–0.87) and SPE was 0.82 (95% CI: 0.72–0.89). In the conventional contrast enhanced (CE)-MRI subgroup, PET/CT outperformed conventional CE-MRI with a higher pooled sensitivity (0.88 (95% CI: 0.71, 0.95) vs. 0.74 (95% CI: 0.60, 0.85), P = 0.018). In the early evaluation subgroup, PET/CT was superior to MRI with a notable higher pooled specificity (0.94 (95% CI: 0.78, 0.98) vs. 0.83 (95% CI: 0.81, 0.87), P = 0.015). The diagnostic performance of MRI is similar to that of PET/CT for the assessment of breast cancer response to NAC. However, PET/CT is more sensitive than conventional CE-MRI and more specific if the second imaging scan is performed before 3 cycles of NAC.

Background: Cognitive dysfunction is considered a core feature among schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). Despite abundant literature comparing cognitive dysfunction among these disorders, the relationship between cognitive dysfunction and symptom dimensions remains unclear. The study aims are a) to identify the factor structure of the BPRS-18 and b) to examine the relationship between symptom domains and cognitive function across SZ, BD, and MDD.Methods: A total of 716 participants [262 with SZ, 104 with BD, 101 with MDD, and 249 healthy controls (HC)] were included in the study. One hundred eighty participants (59 with SZ, 23 with BD, 24 with MDD, and 74 HC) completed the MATRICS Consensus Cognitive Battery (MCCB), and 507 participants (85 with SZ, 89 with BD, 90 with MDD, and 243 HC) completed the Wisconsin Card Sorting Test (WCST). All patients completed the Brief Psychiatric Rating Scale (BPRS).Results: We identified five BPRS exploratory factor analysis (EFA) factors (“affective symptoms,” “psychosis,” “negative/disorganized symptoms,” “activation,” and “noncooperation”) and found cognitive dysfunction in all of the participant groups with psychiatric disorders. Negative/disorganized symptoms were the most strongly associated with cognitive dysfunctions across SZ, BD, and MDD.Conclusions: Our findings suggest that cognitive dysfunction severity relates to the negative/disorganized symptom domain across SZ, BD, and MDD, and negative/disorganized symptoms may be an important target for effective cognitive remediation in SZ, BD, and MDD.

Background: It is important to achieve the definitive pathogen identification in hospital-acquired pneumonia (HAP), but the traditional culture results always delay the target antibiotic therapy. We assessed the method called quantitative loop-mediated isothermal amplification (qLAMP) as a new implement for steering of the antibiotic decision-making in HAP. Methods: Totally, 76 respiratory tract aspiration samples were prospectively collected from 60 HAP patients. DNA was isolated from these samples. Specific DNA fragments for identifying 11 pneumonia-related bacteria were amplified by qLAMP assay. Culture results of these patients were compared with the qLAMP results. Clinical data and treatment strategies were analyzed to evaluate the effects of qLAMP results on clinical data. McNemar test and Fisher′s exact test were used for statistical analysis. Results: The detection of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Stenotrophomonas maltophilia, Streptococcus pneumonia, and Acinetobacter baumannii by qLAMP was consistent with sputum culture (P > 0.05). The qLAMP results of 4 samples for Haemophilus influenzae, Legionella pneumophila, or Mycoplasma pneumonia (MP) were inconsistent with culture results; however, clinical data revealed that the qLAMP results were all reliable except 1 MP positive sample due to the lack of specific species identified in the final diagnosis. The improvement of clinical condition was more significant (P < 0.001) in patients with pathogen target-driven therapy based on qLAMP results than those with empirical therapy. Conclusion: qLAMP is a more promising method for detection of pathogens in an early, rapid, sensitive, and specific manner than culture.

S100A4, a calcium-binding protein, can promote pulmonary fibrosis via fibroblast activation. Due partly to its various cellular origins, the exact role of S100A4 in the development of lung fibrosis remains elusive. Here, we show that in the bronchoalveolar lavage fluid, numbers of S100A4+ macrophages correlated well with S100A4 protein levels and occurrence of idiopathic pulmonary fibrosis (IPF) in patients. A mouse model of bleomycin-induced pulmonary fibrosis demonstrated S100A4+ macrophages as main source for extracellular S100A4 in the inflammatory phase. In vitro studies revealed that extracellular S100A4 could activate both mouse and human lung fibroblasts by upregulation of α-SMA and type I collagen, during which sphingosine-1-phosphate (S1P) increased. Inhibiting the S1P receptor subtypes S1P1/S1P3 abrogated fibroblast activation. Accordingly, absence or neutralization of S100A4 significantly attenuated bleomycin-induced lung fibrosis in vivo. Importantly, adoptive transfer of S100A4+ but not of S100A4− macrophages installed experimental lung injury in S100A4−/− mice that were otherwise not sensitive to fibrosis induction. Taken together, S100A4 released by macrophages promotes pulmonary fibrosis through activation of lung fibroblasts which is associated with S1P. This suggests that extracellular S100A4 or S100A4+ macrophages within the lung as promising targets for early clinical diagnosis or therapy of IPF.

A novel strain of influenza A(H7N9) virus has emerged in China and is causing mild to severe clinical symptoms in infected humans. Some case-patients have died. To further knowledge of this virus, we report the characteristics and clinical histories of 4 early case-patients.

OBJECTIVE: To use direct comparative studies or randomised controlled trials to compare the accuracy of cardiac magnetic resonance (CMR) and single-photon emission computed tomography (SPECT) for the detection of obstructive coronary artery disease (CAD). MATERIALS AND METHODS: Various databases were searched for original articles published prior to June 2013. Studies were selected that performed both CMR and SPECT in the same or randomised patients to detect CAD and that presented sufficient data to allow construction of contingency tables. For each study, the true-positive, false-positive, true-negative, and false-negative values were extracted or derived, and 2 × 2 contingency tables were constructed. To reduce heterogeneity, the meta-analysis was carried out in two parts: (1) coronary territory-based analysis and (2) patient-based analysis. RESULTS: 10 studies (5 studies based on patient, 4 studies based on coronary territory, and 1 study based on both) were included in the meta-analysis with a total of 1727 patients. The methodological quality was moderate. For part (1), the summary estimates were as follows: for CMR based on patient-a sensitivity of 0.79 (95% confidence interval: 0.72-0.84) and a specificity of 0.75 (0.65-0.83); for SPECT based on patient-a sensitivity of 0.70 (0.59-0.79) and a specificity of 0.76 (0.66-0.83). For part (2), the summary estimates for CMR based on coronary territory were a sensitivity of 0.80 (0.73-0.85) and a specificity of 0.87 (0.81-0.91), and the summary estimates for SPECT based on coronary territory were a sensitivity of 0.67 (0.60-0.72) and a specificity of 0.80 (0.75-0.84). CONCLUSIONS: Compared with SPECT, CMR is more sensitive to detect CAD on a per-patient basis. Nonetheless, large scale, well-designed trials are necessary to assess its clinical value on a per-coronary territory basis.

BACKGROUND: Reduced overall survival has been observed in patients with left-sided versus right-sided breast cancer due to cardiac toxicity after radiotherapy. However, the effect of laterality and primary tumor site on breast cancer-specific mortality (BCSM) remains unclear. PATIENTS AND METHODS: We analyzed data from 305,443 women ages 20- to 79-years-old diagnosed with breast cancer between 1990 and 2009. The data were obtained from the population-based Surveillance, Epidemiology, and End Results (SEER) program of the U.S. National Cancer Institute. The survival outcomes with regard to laterality and primary tumor site were compared using univariate and multivariate (Cox proportional hazards regression model) methods. RESULTS: In the multivariate analysis, BCSM was affected by the primary tumor site (P

OBJECTIVE: To perform a meta-analysis exploring the correlation between the apparent diffusion coefficient (ADC) and tumor cellularity in patients. MATERIALS AND METHODS: We searched medical and scientific literature databases for studies discussing the correlation between the ADC and tumor cellularity in patients. Only studies that were published in English or Chinese prior to November 2012 were considered for inclusion. Summary correlation coefficient (r) values were extracted from each study, and 95% confidence intervals (CIs) were calculated. Sensitivity and subgroup analyses were performed to investigate potential heterogeneity. RESULTS: Of 189 studies, 28 were included in the meta-analysis, comprising 729 patients. The pooled r for all studies was -0.57 (95% CI: -0.62, -0.52), indicating notable heterogeneity (P

OBJECTIVE: To determine the accuracy of MR imaging with Gd-EOB-DTPA for the detection of liver metastases. MATERIALS AND METHODS: PUBMED, EMBASE, the Web of Science, and the Cochrane Library were searched for original articles published prior to February 2012. The criteria for the inclusion of articles were as follows: reported in the English language; MR imaging with Gd-EOB-DTPA was performed to detect liver metastases; histopathologic analysis (surgery, biopsy), intraoperative observation (manual palpatation, intraoperative ultrasonography), and/or follow-up US was the reference standard; and data were sufficient for the calculation of true-positive or false-negative values. The methodological quality was assessed by using the quality assessment of diagnostic studies instrument. The data were extracted to calculate sensitivity, specificity, predictive value, diagnostic odds ratio, and areas under hierarchical summary receiver operating characteristic (HSROC) curve to perform heterogeneity test and threshold effect test, as well as publication bias analysis and subgroup analyses. RESULTS: From 229 citations, 13 were included in the meta-analysis with a total of 1900 lesions. We detected heterogeneity between studies and evidence of publication bias. The methodological quality was moderate. The pooled weighted sensitivity with a corresponding 95% confidence interval (CI) was 0.93 (95% CI: 0.90, 0. 95), the specificity was 0.95 (95% CI: 0.91, 0.97), the positive likelihood ratio was 18.07 (95% CI: 10.52, 31.04), the negative likelihood ratio was 0.07 (95% CI: 0.05, 0.10), and the diagnostic odds ratio was 249.81 (95% CI: 125.12, 498.74). The area under the receiver operator characteristic curve was 0.98 (95% CI: 0.96, 0.99). CONCLUSION: MR imaging with Gd-EOB-DTPA is a reliable, non-invasive, and no-radiation-exposure imaging modality with a high sensitivity and specificity for detection of liver metastases. Nonetheless, it should be applied cautiously, and large scale, well-designed trials are necessary to assess its clinical value.