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Introduction: A survival paradox between T4N0 (Stage IIB/IIC) and Stage IIIA colon cancer exists, even after adjusting for adequate lymph node (LN) retrieval and receipt of adjuvant chemotherapy (C). We conducted a large hospital-based study to re-evaluate this survival paradox based on the newest 8th edition staging system. Methods: The National Cancer Data Base was queried to evaluate 35,606 patients diagnosed with Stage IIB, IIC, and IIIA colon cancer between 2010 and 2017. The Kaplan–Meier method and log-rank test were used to compare unadjusted overall survival (OS). Multivariable Cox proportional hazards model was used to determine the association of stage with hazard ratios adjusted for relevant demographic and clinical variables including ≥ 12 LNs retrieved and receipt of adjuvant chemotherapy. P value < 0.05 was considered statistically significant. Results: The 5-year OS for optimally treated stage IIIA colon cancer (receipt of C) was 84.3%, which was significantly higher than stage IIB/C (≥ 12 LNs retrieved + C) (72.8%; P < 0.0001). Stage was an independent predictor of OS. Among optimally treated Stage IIIA patients, T1N1 had the best survival (90.6%) while stage T4bN0 (stage IIC) had the worst (70.9%) (P < 0.0001). Compared to stage IIB, stage IIC had a 17% increased risk of overall death while stage IIIA had a 21% reduction in death (P < 0.0001). Conclusion: Stage IIB/C and Stage IIIA survival paradox persists even after accounting for receipt of adjuvant chemotherapy and adequate lymph node retrieval. Future iteration of the TNM system should take this paradox into consideration. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of manual acupuncture on endometrial blood flow parameters by three-dimensional (3D) power Doppler ultrasound in women undergoing in vitro fertilization embryo transfer (IVF-ET). Methods: Seventy patients undergoing IVF-ET were equally randomized into traditional or sham acupuncture treatment group for totally 4 days (from the day of oocyte aspiration to the day of embryo transfer) of treatment by random envelope method at the Reproductive Medicine Center and Outpatient Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology from January 2013 to December 2015. Patients in the traditional acupuncture group accepted traditional acupuncture methods with manual acupuncture, and Zhongji (CV3), Qihai (CV 6), Sanyinjiao (SP6), Taichong (LR 3), Tianshu (ST 25), Guilai (ST 29) and Zusanli (ST 36) were chosen. Patients at the sham acupuncture group accepted shallow acupuncture methods at 4 non-meridian points at each shoulder and upper arm. Outcome measures included endometrial ultrasonic indices such as vascularization index (VI), flow index (FI) and vascularization flow index (VFI), endometrial thickness and volume, subendometrial VI (sVI), subendometrial FI (sFI), subendometrial VFI (sVFI), implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births. Results: Finally, 34 patients in the traditional acupuncture group and 35 in the sham acupuncture group completed this trial. VI, FI and VFI of the traditional acupuncture group were significantly higher than those in the sham acupuncture group (P<0.05). No significant differences were found in endometrial thickness, endometrial volume, sVI, sFI, sVFI, implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births (P>0.05). Conclusions: Manual acupuncture performed after oocyte aspiration and before transplantation improved the endometrial blood flow parameters VI, RI and VFI in women who underwent IVF-ET, instead of sVI, sFI and sVFI. Therefore, acupuncture might be beneficial in women undergoing IVF-ET by increasing endometrial blood flow and endometrial receptivity. (Registration No. ChiCTR2100053354) [ABSTRACT FROM AUTHOR]

Objective: To analyze the differences in the needs of users and the value orientation of clinical practice guidelines (CPGs) by comparing the contents and formation methods of clinical questions in Chinese and Korean CPGs of acupuncture-moxibustion (Acup-Mox). Methods: The full text of CPGs was systematically searched from the official websites of Chinese and Korean traditional medicine societies and Acup-Mox associations, with the topic "Acup-Mox for treating diseases" and the retrieval time up to September 28, 2022. Two researchers screened the CPGs independently, and extracted the guidelines' topics, content, quantity and formation methods of clinical questions. The quantitative data were collected by counting the frequency, and the qualitative data were classified and described by thematic analysis. Results: A total of 29 guidelines were included in this study, including 20 Chinese guidelines (305 questions) and 9 Korean guidelines (223 questions). The differences lie in the aspects of content and diversity, and formation method. As for content and diversity, Chinese guidelines focused mainly on the questions related to treatment such as the operation of specific intervention (86, 28.2%), efficacy of intervention (78, 25.6%), and also involving questions in diagnosis, prevention, and prognosis. While the clinical questions in Korean guidelines were concentrated to efficacy of intervention (218, 97.8%). As for formation method, in Chinese guidelines, questions were usually collected directly from clinicians, and then determined and optimized by experts. In Korean guidelines, frequently used clinical Acup-Mox interventions would be screened first. Then the expert group would set up corresponding intervention control measures so as to form clinical questions related to treatment efficacy. Conclusions: The differences reflect the different needs of clinical practitioners, and the different aims or concepts in developing Acup-Mox guidelines between China and South Korea. Chinese guidelines emphasized promoting operation protocols and techniques of Acup-Mox for practical use, while Korean guidelines emphasized promoting the frequently used clinical intervention therapies. It is speculated that the guidelines from these two countries would play different roles in guiding clinical operation and supporting medical decision. In terms of formation methods of clinical questions, it is suggested to attach importance to optimizing process in formatting clinical questions to improve the clinical applicability of CPGs of Acup-Mox. [ABSTRACT FROM AUTHOR]

Objective. The aim of the study is to investigate the serum metabolomics of electroacupuncture (EA) with different current intensities in the treatment of functional constipation (FC). Methods. The total number of FC patients was 19, (7, 6, 6, in the low current intensity group (LCI), high current intensity group (HCI), and mosapride citrate tablet control group (MC), respectively). Patients in the EA groups received 16 sessions of acupuncture treatments. Patients in the MC group were orally administered 5 mg mosapride citrate tablets 3 times daily, and serum samples were collected from the patients before and after treatment. Orthogonal partial least square-discriminant analysis (OPLS-DA) was used to assess the metabolic data. The significant differences before and after FC treatment are shown in the OPLS-DA score plot. Variable importance plots (VIPs) and T tests were used to identify significant metabolites. Results. Among the three groups, the number of metabolites with VIP > 1 was 11, 7, and 21 (in LCI, HCI and MC groups, respectively). Compared with those before treatment, the serum metabolites of patients were characterized by increased levels of L-ornithine (p < 0.05) and glyceric acid in the LCI group (p < 0.05), increased levels of vanillic acid in the MC group (p < 0.05), and decreased levels of arabinonic acid in the MC group (p < 0.05). Conclusions. The effects of EA treatment on the serum metabolomics of FC may involve fatty acid and amino acid metabolism. [ABSTRACT FROM AUTHOR]

The Yangtze River Delta and Pearl River Delta are two regions with the highest level of economic development in China, and their port development is at the forefront of the country. This study measures the efficiency of 23 major ports in the two deltas from 2010 to 2018 using the meta Dynamic Directional Distance Function (D.D.F.) model and discusses the technology gap and the reasons for inefficiency of the ports. The research results show that 80% of the ports in these two deltas are inefficient. The Yangtze River Delta's port efficiency is higher than that of the Pearl River Delta, but the internal efficiency difference of the Yangtze River Delta port cluster is more significant. The efficiency ranking of most ports is inconsistent under the meta-frontier (M.F.) and group frontier (G.F.), and the average technology gap ratio (T.G.R.) of ports in the Pearl River Delta gradually exceeds that in the Yangtze River Delta. The inefficiency of ports in the Pearl River Delta is caused by input factors, and the inefficiency of ports in the Yangtze River Delta is also related to the containerisation level. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a neuroinflammatory disease characterized by CD4 + T cell-mediated immune cell infiltration and demyelination in the central nervous system (CNS). The subtypes of CD4 + T cells are T helper cells 1 (Th1), Th2, Th17, and regulatory T cells (Treg), while three other types of cells besides Th2 play a key role in MS and its classic animal model, experimental autoimmune encephalomyelitis (EAE). Tregs are responsible for immunosuppression, while pathogenic Th1 and Th17 cells cause autoimmune-associated demyelination. Therefore, suppressing Th1 and Th17 cell differentiation and increasing the percentage of Treg cells may contribute to the treatment of EAE/MS. Astragali Radix (AR) is a representative medicine with immunoregulatory, anti-inflammatory, antitumor, and neuroprotective effects.The active ingredients in AR include astragalus flavones, polysaccharides, and saponins. In this study, it was found that the total flavonoids of Astragus (TFA) could effectively treat EAE in mice by ameliorating EAE motor disorders, reducing inflammatory damage and demyelination, inhibiting the proportion of Th17 and Th1 cells, and promoting Tregs differentiation by regulating the JAK/STAT and NF κ B signaling pathways. This novel finding may increase the possibility of using AR or TFA as a drug with immunomodulatory effects for the treatment of autoimmune diseases. [ABSTRACT FROM AUTHOR]

Background: Osteoporotic vertebral compression fractures (OVCF) are common in aged population with bone fragility. This study aimed to identify the radiographic and bone fragility characteristic of acute single and multiple OVCF. Methods: OVCF patients hospitalized in a spine center between June 2016 and October 2020 were retrospectively studied. Demographics, comorbidity, bone mineral density, spine trauma, duration of pre-hospital back pain, anatomical location and distribution pattern of OVCF, extent of vertebral marrow edema, and degree of vertebral compression of patients with multi-segment vertebral fractures (MSVF) were summarized and compared to those with single segment vertebral fractures (SSVF). Results: A total of 1182 patients with 1530 acute fractured vertebrae were included. There were 944 SSVF (79.9%) and 238 MSVF (20.1%) simultaneously involving two (MSVF-2) or three and more vertebra (MSVF-3/m). The Female-Male ratio was 4.4 and differed not significantly between SSVF and MSVF. Females in SSVF were younger than males while MSVF-2 tended to occur in older females. L1, T12, and L2 were the three most frequently fractured vertebra and MSVF involved more vertebra in thoracic and lumbar spine. 31.1% in MSVF-2 and 83.1% in MSVF-3/m had at least two vertebral fractures in adjacent. The fractured thoracolumbar vertebra in MSVF was less compressed than that in SSVF. Apparent spine trauma was reported by 61.4% of SSVF, 44.1% of MSVF-2, and 36.3% of MSVF-3/m, while early hospitalization with pre-hospital back pain ≤ 1 week was 58.9% in SSVF, 45.3% in MSVF-2, and 25.9% in MSVF-3/m. Only females aged 70–80 years old in MSVF-3/m showed lower baseline bone mineral density than in MSVF-2 and SSVF. MSVF were not associated with increased comorbidity of hypertension, diabetes, coronary heart disease, cerebral infarction, and chronic pulmonary disease. Conclusions: 20% of acute OVCF can involve multiple vertebra without significant spine trauma or lower baseline bone mineral density. Multiple OVCF tend to occur in adjacent vertebra with less thoracolumbar vertebral compression but longer duration of pre-hospital back pain. [ABSTRACT FROM AUTHOR]

Metabolic disorder is highly related to obesity, insulin resistance, hypertension, and hyperlipidemia. The present study found that astragaloside IV (ASI) attenuated metabolic disorder related symptoms and modulated hepatic lipid metabolism associated gene mRNA expression in db/db mice. ASI inhibited rosiglitazone-induced adipocyte differentiation of 3T3-L1 cells, and lipid accumulation in palmitic acid (PA)-induced HepG2 cells with down-regulated mRNA expression of lipogenesis-related genes. In addition, it was predicted to bind to the ligand binding domain (LBD) of PPARγ and inhibit its transactivity. Collectively, our study suggested that ASI improves lipid metabolism in obese mice probably through suppressing PPARγ activity. [ABSTRACT FROM AUTHOR]

Objective: To compare non-tuberculous mycobacterial pulmonary disease (NTMPD) diagnosis by metagenomic next-generation sequencing (mNGS) with Bactec mycobacterial growth indicator tube (MGIT) 960. Methods: A total of 422 patients with suspected NTMPD in Shanghai Pulmonary Hospital between January 2020 and May 2021 were retrospectively analyzed; 194 were diagnosed with NTMPD. The diagnostic performance of mNGS and MGIT 960 for NTMPD was assessed. Receiver operating characteristic (ROC) curves and areas under curve (AUCs) were compared. Results: The sensitivity of mNGS in NTMPD diagnosis was 81.4% and higher than that of MGIT 960 (53.6%). The specificity of mNGS in NTMPD diagnosis was 97.8%, similar to that of MGIT 960 (100%). The sensitivity of combined mNGS and MGIT 960 in NTMPD diagnosis was 91.8%. The sensitivity of mNGS for bronchoalveolar lavage fluid (BALF), pulmonary puncture tissue fluid, and sputum was 84.8%, 80.6%, and 77.5%, respectively; all were higher than that of MGIT 960 (P < 0.05). The AUC of mNGS and MGIT 960 was 0.897 and 0.768, respectively. The AUC of mNGS were BALF (0.916), pulmonary puncture tissue fluid (0.903), and sputum (0.870). Conclusion: The sensitivity of mNGS was superior to that of Bactec MGIT 960; the specificity in NTMPD diagnosis was similar. mNGS shows effective performance in NTMPD diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: The multicenter study aimed to explore the relationship between the growth pattern of liver metastases on preoperative MRI and early recurrence in patients with colorectal cancer liver metastases (CRCLM) after surgery.Methods: A total of 348 CRCLM patients from 3 independent centers were enrolled, including 130 patients with 339 liver metastases in the primary cohort and 218 patients in validation cohorts. Referring to the gross classification of hepatocellular carcinoma (HCC), the growth pattern of each liver metastasis on MRI was classified into four types: rough, smooth, focal extranodular protuberant (FEP), and nodular confluent (NC). Disease-free survival (DFS) curve was constructed using the Kaplan-Meier method.Results: In primary cohort, 42 (12.4%) of the 339 liver metastases were rough type, 237 (69.9%) were smooth type, 29 (8.6%) were FEP type, and 31 (9.1%) were NC type. Those patients with FEP- and/or NC-type liver metastases had shorter DFS than those without such metastases (p < 0.05). However, there were no significant differences in DFS between patients with rough- and smooth-type liver metastases and those without such metastases. The patients with FEP- and/or NC-type liver metastases also had shorter DFS than those without such metastases in two external validation cohorts. In addition, 40.5% of high-risk-type (FEP and NC) liver metastases converted to low-risk types (rough and smooth) after neoadjuvant chemotherapy.Conclusion: The FEP- and NC-type liver metastases were associated with early recurrence, which may facilitate the clinical treatment of CRCLM patients.Key Points: • In the primary cohort, patients with FEP- and NC-type metastases had shorter disease-free survival (DFS) and a higher intrahepatic recurrence rate than patients without such metastases in the liver. • In the primary cohort, there were no significant differences in DFS or intrahepatic recurrence rate between patients with rough- and smooth-type metastases and those without such metastases in the liver. • High-risk patients had shorter DFS and a higher intrahepatic recurrence rate than low-risk patients in primary and external validation cohorts. [ABSTRACT FROM AUTHOR]

The present study evaluated effects of dietary supplementation with tryptophan (Trp) on muscle growth, protein synthesis and antioxidant capacity in hybrid catfish Pelteobagrus vachelli♀ × Leiocassis longirostris♂. Fish were fed six different diets containing 2·6 (control), 3·1, 3·7, 4·2, 4·7 and 5·6 g Trp/kg diet for 56 d, respectively. Results showed that dietary Trp significantly (1) improved muscle protein content, fibre density and frequency of fibre diameter; (2) up-regulated the mRNA levels of PCNA, myf5, MyoD1, MyoG, MRF4, IGF-I, IGF-II, IGF-IR, PIK3Ca, TOR, 4EBP1 and S6K1; (3) increased phosphorylation levels of AKT, TOR and S6K1; (4) decreased contents of MDA and PC, and increased activities of CAT, GST, GR, ASA and AHR; (5) up-regulated mRNA levels of CuZnSOD, CAT, GST, GPx, GCLC and Nrf2, and decreased Keap1 mRNA level; (6) increased nuclear Nrf2 protein level and the intranuclear antioxidant response element-binding ability, and reduced Keap1 protein level. These results indicated that dietary Trp improved muscle growth, protein synthesis as well as antioxidant capacity, which might be partly related to myogenic regulatory factors, IGF/PIK3Ca/AKT/TOR and Keap1/Nrf2 signalling pathways. Finally, based on the quadratic regression analysis of muscle protein and MDA contents, the optimal Trp requirements of hybrid catfish (21·82–39·64 g) were estimated to be 3·94 and 3·93 g Trp/kg diet (9·57 and 9·54 g/kg of dietary protein), respectively. [ABSTRACT FROM AUTHOR]

Background. Treatment based on syndrome differentiation under the traditional Chinese medicine (TCM) framework has been shown to be helpful in patients with coronary artery disease. We hypothesized that syndrome types could predict the risk of type 2 myocardial infarction (T2MI) caused by imbalance between myocardial oxygen supply and demand in critically ill patients with pulmonary disease. Methods. This retrospective study included consecutive critically ill patients with pulmonary disease admitted to the ICU at Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences from January 1, 2017, to July 1, 2019. Diagnosis of T2MI was based on the fourth universal definition of myocardial infarction. Risk factors associated with T2MI were identified using multivariate regression analysis. Results. A total of 244 patients were included in the study: 78 who developed T2MI and the remaining 166 who did not develop T2MI during hospitalization. The incidence of phlegm syndrome and deficiency syndrome was 61.9% and 38.1%, respectively. In comparison with the patients with phlegm syndrome, the incidence of T2MI in patients with deficiency syndrome is significantly higher (40.9% vs. 26.5%, P = 0.019). In multivariate logistic regression, T2MI was independently associated with the baseline troponin level (OR 12.682, 95% CI 1.397∼115.121; P = 0.024), hemoglobin < 55 g/L (OR 12.76, 95% CI 2.359∼69.021; P = 0.003), mechanical ventilation (OR 2.244, 95% CI 1.029∼4.892; P = 0.042), and TCM deficiency syndrome (OR 2.214, 95% CI 1.032∼4.749; P = 0.041). After adjusting for confounding factors in Cox regression models, the hazard ratio (95% confidence interval) of qi deficiency syndrome groups was 1.183 (95% CI 1.053∼3.123, P = 0.032). Conclusions. Patients with deficiency syndrome are at high risk of T2MI, especially those combined with qi deficiency syndrome. [ABSTRACT FROM AUTHOR]

Background: Triage for suspected acute stroke has two main options: (1) transport to the closest primary stroke center (PSC) and then to the nearest comprehensive stroke center (CSC) (Drip-and-Ship) or (2) transport the patient to the nearest CSC, bypassing a closer PSC (mothership). The purpose was to evaluate the effectiveness of drip-and-ship versus mothership models for acute stroke patients. Methods: A Markov decision-analytic model was constructed. All model parameters were derived from recent medical literature. Our target population was adult patient with sudden onset of acute stroke within 8 h of onset over a one-year horizon. The primary outcome was quantified in terms of quality-adjusted-life-years (QALYs). Results: The base case scenario show that the drip-and-ship strategy has a slightly higher expected health benefit, 0.591 QALY, as compared to 0.586 QALY in the mothership strategy when the time to PSC is 30 min and to CSC is 65 min, although the difference in health benefit becomes minimal as the time to PSC increases towards 60 min. Multiple sensitivity analyses show that when both PSC and CSC are far from place of onset (>1.5 h away), drip-and-ship becomes the better strategy. Mothership strategy is favored by smaller difference between distances to PSC and CSC, shorter transfer time from PSC to CSC, and longer delay in reperfusion in CSC for transferred patients. Drip-and-ship is favored by the reverse. Conclusion: Drip-and-ship has a slightly higher utility than mothership. This study assesses the complex issue of prehospital triage of acute stroke patients and can provide a framework for real-world data input. [ABSTRACT FROM AUTHOR]

Context: Patients with gastric cancer experience health-related quality of life (HRQOL) decline during adjuvant chemotherapy following gastrectomy.Objectives: This pilot study aimed to evaluate the preliminary effect and feasibility of electro-acupuncture (EA) for HRQOL and symptom burden in these patients.Methods: In this open-label, multicenter, parallel controlled trial, gastric cancer patients who planned to receive adjuvant chemotherapy were randomly assigned to receive high-dose EA (seven times each chemotherapy cycle for three cycles), low-dose EA (three times each chemotherapy cycle), or usual care only. The acupoints prescription consisted of bilateral ST36, PC6, SP4, and DU20, EX-HN3, and selected Back-shu points. Patients completed the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) weekly, and the Edmonton Symptom Assessment System (ESAS). The primary outcome was the difference among the groups on the gastric cancer subscale (GaCS) of the FACT-Ga.Results: Of the 66 randomized patients, 58 were analyzed according to intention-to-treat principle, and 45 were in the per-protocol set (PPS). The average scores in PPS of GaCS were 52.12±9.71, 51.85±12.36, and 45.37±8.61 in high-dose EA, low-dose EA, and control groups, respectively. EA was significantly associated with improved average GaCS scores when compared with control group (51.98±10.91 vs. 45.37±8.61, P = 0.039). EA treatment also produced ESAS relief at the end of intervention (14.36 ± 12.28 vs. 23.91 ± 15.52, P = 0.027). Participants in EA groups had fewer grade ≥3 leukopenia (0% vs. 15.79%, P = 0.031) and neutropenia (2.56% vs. 26.31%, P = 0.012).Conclusion: EA showed promising effects in improving HRQOL, controlling symptom burden, and reducing toxicity during adjuvant chemotherapy in gastric cancer patients. Future adequately powered trials are feasible and needed to confirm the specific effect of EA. [ABSTRACT FROM AUTHOR]

Background: To inform patients who are in the process of selecting prostate cancer treatment, the authors compared disease‐specific function after external‐beam radiotherapy (EBRT) alone versus EBRT plus a low‐dose‐rate (LDR) brachytherapy boost (EBRT‐LDR). Methods: For this prospective study, men who had localized prostate cancer in 2011 and 2012 were enrolled. Assessments at baseline, 0.5, 1, 3, and 5 years included the patient‐reported Expanded Prostate Index Composite, the 36‐item Medical Outcomes Study Short‐Form Health Survey, and treatment‐related regret. Regression models were adjusted for baseline function and for patient and treatment characteristics. The minimum clinically important difference in scores on the Expanded Prostate Index Composite 26‐item instrument was from 5 to 7 for urinary irritation and from 4 to 6 for bowel function. Results: Six‐hundred ninety‐five men met inclusion criteria and received either EBRT (n = 583) or EBRT‐LDR (n = 112). Patients in the EBRT‐LDR group were younger (median age, 66 years [interquartile range [IQR], 60‐71 years] vs 69 years [IQR, 64‐74 years]; P <.001), were less likely to receive pelvic radiotherapy (10% vs 18%; P =.040), and had higher baseline 36‐item Medical Outcomes Study Short‐Form Health Survey physical function scores (median score, 95 [IQR, 86‐100] vs 90 [IQR, 70‐100]; P <.001). Over a 3‐year period, compared with EBRT, EBRT‐LDR was associated with worse urinary irritative scores (adjusted mean difference at 3 years, −5.4; 95% CI, −9.3, −1.6) and bowel function scores (−4.1; 95% CI, −7.6, −0.5). The differences were no longer clinically meaningful at 5 years (difference in urinary irritative scores: −4.5; 95% CI, −8.4, −0.5; difference in bowel function scores: −2.1; 95% CI, −5.7, −1.4). However, men who received EBRT‐LDR were more likely to report moderate or big problems with urinary function bother (adjusted odds ratio, 3.5; 95% CI, 1.5‐8.2) and frequent urination (adjusted odds ratio, 2.6; 95% CI, 1.2‐5.6) through 5 years. There were no differences in survival or treatment‐related regret between treatment groups. Conclusions: Compared with EBRT alone, EBRT‐LDR was associated with clinically meaningful worse urinary irritative and bowel function over 3 years after treatment and more urinary bother at 5 years. Lay Summary: In men with prostate cancer who received external‐beam radiation therapy (EBRT) with or without a brachytherapy boost (EBRT‐LDR), EBRT‐LDR was associated with clinically worse urinary irritation and bowel function through 3 years but resolved after 5 years.Men who received EBRT‐LDR continued to report moderate‐to‐big problems with urinary function bother and frequent urination through 5 years.There was no difference in treatment‐related regret or survival between patients who received EBRT and those who received EBRT‐LDR.These intermediate‐term estimates of function may facilitate counseling for men who are selecting treatment. Among men with prostate cancer who receive external‐beam radiation therapy with or without brachytherapy boost, a clinically worse decline in urinary irritation and bowel function is observed through 3 years in the brachytherapy group. Through 5 years, these symptoms are no longer clinically meaningful; however, patients in the brachytherapy group continue to report moderate‐to‐large problems with urinary function bother and frequent urination. [ABSTRACT FROM AUTHOR]

Background: The pine wood nematode (PWN), Bursaphelenchus xylophilus, is a devastating pathogen of many Pinus species in China. The aim of this study was to understand the interactive molecular mechanism of PWN and its host by comparing differentially expressed genes and candidate effectors from three transcriptomes of B. xylophilus at different infection stages. Results: In total, 62, 69 and 46 candidate effectors were identified in three transcriptomes (2.5 h postinfection, 6, 12 and 24 h postinoculation and 6 and 15 d postinfection, respectively). In addition to uncharacterized pioneers, other candidate effectors were involved in the degradation of host tissues, suppression of host defenses, targeting plant signaling pathways, feeding and detoxification, which helped B. xylophilus survive successfully in the host. Seven candidate effectors were identified in both our study and the B. xylophilus transcriptome at 2.5 h postinfection, and one candidate effector was identified in all three transcriptomes. These common candidate effectors were upregulated at infection stages, and one of them suppressed pathogen-associated molecular pattern (PAMP) PsXEG1-triggered cell death in Nicotiana benthamiana. Conclusions: The results indicated that B. xylophilus secreted various candidate effectors, and some of them continued to function throughout all infection stages. These various candidate effectors were important to B. xylophilus infection and survival, and they functioned in different ways (such as breaking down host cell walls, suppressing host defenses, promoting feeding efficiency, promoting detoxification and playing virulence functions). The present results provide valuable resources for in-depth research on the pathogenesis of B. xylophilus from the perspective of effectors. [ABSTRACT FROM AUTHOR]

Background: Given that major depression is a global public health problem, and that sub-threshold depression (SD) has been shown to be a significant risk indicator of major depression disorder, the awareness of SD interventions has increased. The current study explored the effect of increasing cognitive load on the forgetting of unwanted and negative memories of sub-threshold depression individuals (SDs) (Study 1) and proposed a cognitive load intervention (CLI) (study 2).Methods: 53 SDs and 52 normal participants were recruited to explore the effect of cognitive load on the directed forgetting of negative items (Study 1). The treatment effect of CLI on 62 SDs was investigated. SDs completed up to 8 CLI/control sessions over an 8-week period while regularly recording their depression symptoms (Study 2).Results: The results showed that it is more difficult for SDs to forget negative 'to-be-forgotten' items than normal controls (F (1, 99) = 27.98, p < 0.001, η2 = 0.22). In study 1, increasing cognitive load promoted directed forgetting for negative items in SDs. Study 2 showed that there were significant reductions in depression symptoms of SDs over the 8-week CLI (e.g. BDI-Ⅱ scores: F (1, 60) = 99.93, p < 0.001, η2 = 0.63).Limitations: Small sample size and lack of verification by neuroimaging may limit the generalizability of these results.Conclusions: The study revealed that increasing cognitive load can promote SDs to forget negative information, while the CLI project effectively reduced the depression level of SDs, thus providing encouraging initial support for its use in the treatment of SD. [ABSTRACT FROM AUTHOR]

Objectives: The present study aimed to discover novel susceptibility loci associated with risk of rheumatoid arthritis (RA).Methods: We performed a new genome-wide association study (GWAS) in Chinese subjects (1027 RA cases and 2879 controls) and further conducted an expanded meta-analysis with previous GWAS summary data and replication studies. The functional roles of the associated loci were interrogated using publicly available databases. Dual-luciferase reporter and cytokine assay were also used for exploring variant function.Results: We identified five new susceptibility loci (IL12RB2, BOLL-PLCL1, CCR2, TCF7 and IQGAP1; pmeta <5.00E-08) with same effect direction in each study cohort. The sensitivity analyses showed that the genetic association of at least three loci was reliable and robust. All these lead variants are expression quantitative trait loci and overlapped with epigenetic marks in immune cells. Furthermore, genes within the five loci are genetically associated with risk of other autoimmune diseases, and genes within four loci are known functional players in autoimmunity, which supports the validity of our findings. The reporter assay showed that the risk allele of rs8030390 in IQGAP1 have significantly increased reporter activity in HEK293T cells. In addition, the cytokine assay found that the risk allele of rs244672 in TCF7 was most significantly associated with increased plasma IL-17A levels in healthy controls. Finally, identified likely causal genes in these loci significantly interacted with RA drug targets.Conclusion: This study identified novel RA risk loci and highlighted that comprehensive genetic study can provide important information for RA pathogenesis and drug therapy. [ABSTRACT FROM AUTHOR]

Background: The optimal sampling techniques for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) remain unclear and have not been standardized. The aim of this study was to compare the wet-suction and dry-suction techniques for sampling solid lesions in the pancreas, mediastinum, and abdomen.Methods: This was a multicenter, crossover, randomized controlled trial with randomized order of sampling techniques. The 296 consecutive patients underwent EUS-FNA with 22G needles and were randomized in a ratio of 1:1 into two separate groups that received the dry-suction and wet-suction techniques in a different order. The primary outcome was to compare the histological diagnostic accuracy of dry suction and wet suction for malignancy. The secondary outcomes were to compare the cytological diagnostic accuracy and specimen quality.Results: Among the 269 patients with pancreatic (n = 161) and non-pancreatic (n = 108) lesions analyzed, the wet-suction technique had a significantly better histological diagnostic accuracy (84.9 % [95 % confidence interval (CI) 79.9 % - 89.0 %] vs. 73.2 % [95 %CI 67.1 % - 78.7 %]; P = 0.001), higher specimen adequacy (94.8 % vs. 78.8 %; P < 0.001), and less blood contamination (P < 0.001) than the dry-suction technique. In addition, sampling non-pancreatic lesions with two passes of wet suction provided a histological diagnostic accuracy of 91.6 %.Conclusions: The wet-suction technique in EUS-FNA generates better histological diagnostic accuracy and specimen quality than the dry-suction technique. Furthermore, sampling non-pancreatic lesions with two passes of EUS-FNA with wet suction may provide a definitive histological diagnosis when rapid on-site evaluation is not routinely available. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the effect of lumbar spine selective nerve root block (SNRB) experience on the learning efficiency of percutaneous endoscopic lumbar discectomy (PELD) for junior trainees.Methods: A total of 480 patients undergoing single-level PELD performed by eight junior trainees were included. The trainees were divided into two groups based on whether they had previous SNRB experience (group A, yes; group B, no). Surgical proficiency was defined as total operation time less than 65 minutes and cumulative radiation exposure time no more than 40 seconds. The learning curve was analyzed by cumulative summation (CUSUM) test. Clinical evaluations included Macnab classification, visual analog scale (VAS)-low back score, VAS-leg score, and Oswestry Disability Index (ODI). Follow-up information at 12 months was also obtained.Results: Integral number of cases before achieving an acceptable surgical level in group A (47.75 ± 2.50 cases) was significantly smaller than that in group B (56.50 ± 1.29 cases, p < 0.05), along with less accumulated failure (18.75 ± 0.96 cases vs. 25.50 ± 1.75 cases, p < 0.05). The two groups were comparable in clinical outcomes. Forty-seven cases of complications were observed, with 17 in group A and 30 in group B (p < 0.05).Conclusion: Previous experience of SNRB improved the performance of PELD with shorter operation time and less radiation exposure. SNRB practice may reduce the complication rate without a significant effect on the recurrence of symptoms and reoperation. [ABSTRACT FROM AUTHOR]

Background: The predominance of onychomycosis has been increasing recently. New medications and treatment modalities are being researched for better saturation of the antifungal agents through the nail plate topically because of the low resilience of some patients for the oral antifungal agents. Treatment of onychomycosis, mainly moderate to severe, can be very challenging, expensive, and time consuming. Objective: The objective of this clinical trial is to compare the efficacy and safety of a manually operated ablative CO2 laser combined with a topical antifungal agent in patients with onychomycosis. Study Design: We conducted an open-label controlled prospective study of 160 eligible patients randomized into control and treatment groups with a 1:1 allocation in the department of dermatology in five different hospitals in Shanghai. It was a 6-month study where both groups were treated with a topical antifungal agent, with the treatment group also receiving ablation by the traditional CO2 laser once a month for the first 3 months. Results: The clinical efficacy and mycological cure rate were significantly higher (p < 0.001) for the treatment group. Three (3.75%) patients from the control group and 18 (25%) patients from the treatment group achieved complete nail clearance along with negative potassium hydroxide and negative culture (primary endpoint) results at 24 weeks. Mycological clearance with at least moderate nail clearance (secondary endpoint) for the treatment group was also significantly higher (p < 0.001) for the laser treatment group. The laser treatment was mildly painful but tolerable by the patients. No drug interactions for both groups were encountered. Conclusions: The ablative CO2 laser is a primitive yet effective modality to be considered for the delivery of topical antifungal agents for the management of mild-to-severe onychomycosis. The laser has good tolerance in patients and is a common equipment found in most dermatology units even those without the latest medical technology. [ABSTRACT FROM AUTHOR]

In developing products for rare diseases, statistical challenges arise due to the limited number of patients available for participation in drug trials and other clinical research. Bayesian adaptive clinical trial designs offer the possibility of increased statistical efficiency, reduced development cost and ethical hazard prevention via their incorporation of evidence from external sources (historical data, expert opinions, and real-world evidence), and flexibility in the specification of interim looks. In this paper, we propose a novel Bayesian adaptive commensurate design that borrows adaptively from historical information and also uses a particular payoff function to optimize the timing of the study's interim analysis. The trial payoff is a function of how many samples can be saved via early stopping and the probability of making correct early decisions for either futility or efficacy. We calibrate our Bayesian algorithm to have acceptable long-run frequentist properties (Type I error and power) via simulation at the design stage. We illustrate our approach using a pediatric trial design setting testing the effect of a new drug for a rare genetic disease. The optimIA R package available at https://github.com/wxwx1993/Bayesian_IA_Timing provides an easy-to-use implementation of our approach. [ABSTRACT FROM AUTHOR]

Background: Primary vaginal melanomas are uncommon and aggressive tumors with poor prognosis, and the development of new targeted therapies is essential. This study aimed to identify the molecular markers occurring in these patients and potentially improve treatment strategies. Materials and Methods: The clinicopathological characteristics of 36 patients with primary vaginal melanomas were reviewed. Oncogenic mutations in BRAF, KIT, NRAS, GNAQ and GNA11 and the promoter region of telomerase reverse transcriptase (TERT) were investigated using the Sanger sequencing. The expression and copy number of programmed death‐ligand 1 (PD‐L1) were also assessed. Results: Mutations in NRAS, KIT, and TERT promoter were identified in 13.9% (5/36), 2.9% (1/34), and 5.6% (2/36) of the primary vaginal melanomas, respectively. PD‐L1 expression and amplification were observed in 27.8% (10/36) and 5.6% (2/36) of cases, respectively. PD‐L1 positive expression and/or amplification was associated with older patients (p =.008). Patients who had NRAS mutations had a poorer overall survival compared with those with a wild‐type NRAS (33.5 vs. 14.0 months; hazard ratio [HR], 3.09; 95% CI, 1.08–8.83). Strikingly, two patients with/without PD‐L1 expression receiving immune checkpoint inhibitors had a satisfying outcome. Multivariate analysis demonstrated that >10 mitoses per mm2 (HR, 2.96; 95% CI, 1.03–8.51) was an independent prognostic factor. Conclusions: NRAS mutations and PD‐L1 expression were most prevalent in our cohort of primary vaginal melanomas and can be potentially considered as therapeutic targets. Implications for Practice: This study used the Sanger sequencing, immunohistochemistry, and fluorescence in situ hybridization methods to detect common genetic mutations and PD‐L1 expression and copy number in 36 primary vaginal melanomas. NRAS mutations and PD‐L1 expression were the most prevalent, but KIT and TERT mutations occurred at a lower occurrence in this rare malignancy. Two patients receiving immune checkpoint inhibitors had a satisfying outcome, signifying that the PD‐L1 expression and amplification can be a possible predictive marker of clinical response. This study highlights the possible prospects of biomarkers that can be used for patient selection in clinical trials involving treatments with novel targeted therapies based on these molecular aberrations. Little is known about the molecular characteristics of primary vaginal melanoma. This article reports on the molecular markers of this rare and aggressive disease, focusing on improvements in treatment strategies. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the relationship between homocysteine (Hcy) and blood pressure variability (BPV) and the relationship between Hcy and left ventricular hypertrophy (LVH) in 102 patients with essential hypertension.Methods: The 102 patients were divided into the Hcy < 10 μmol/L group (n = 47) and the Hcy ≥ 10 μmol/L group (n = 55) according to Hcy concentration. The differences between Hcy and BPV and Hcy and LVH were compared between the two groups. Finally, the correlations between Hcy and BPV and between Hcy and LVH were analyzed.Results: The results showed that there were significant differences between Hcy and BPV and between Hcy and LVH in the two groups. Hcy correlated positively with the coefficient of variation in nighttime diastolic blood pressure and night systolic blood pressure standard deviation (nDBPSD), with correlation coefficients of 0.331 and 0.303 (P < 0.001). At the same time, Hcy correlated positively with interventricular septal thickness and left ventricular posterior wall thickness, which were indicators of LVH, with correlation coefficients of 0.350 and 0.352 (P < 0.001).Conclusions: There was a correlation between Hcy and BPV and between Hcy and LVH. Attention should also be paid to blood Hcy and BPV for patients with essential hypertension. [ABSTRACT FROM AUTHOR]

Multi-hesitant fuzzy sets (MHFSs) are hesitant fuzzy sets (HFSs) with membership function, permitting the same evaluation value to be repeated several times. MHFSs can depict uncertain information more effectively than HFSs. This study defined three outranking relations of multi-hesitant fuzzy numbers (MHFNs), namely strong dominant, weak dominant and indifferent relationships, based on the elimination and choice translating reality (ELECTRE) I method. Thereafter, we discussed the corresponding properties of the three outranking relations. We also presented an extended ELECTRE I method, in which the criteria are correlated to select the optimal alternatives, by combination of outranking relations and Choquet integral. Eventually, an application example of MHFNs was presented, and a comparative analysis was performed based on the same example. [ABSTRACT FROM AUTHOR]

Purpose: To explore the efficacy of treatment for early cesarean scar pregnancy (CSP) and to evaluate the characteristics of women with subsequent mixed mass formation.Methods: Women with CSP, who received UACE followed by evacuation, were retrospectively analyzed. Clinical/sonographic characteristics in patients with or without mixed mass formation were compared.Results: From a total of 395 cases, 105 cases had a pregnancy residual with mixed mass formation. Blood loss and subsequent salvage intervention were significantly lower in patients without mixed mass, although all women retained their uteri. It required 50 days for the mass to resolve, 40 days for β-hCG concentrations to drop back to normal, and 61 days for menses to be restored; all of which were significantly longer than the same indices in women without a mixed mass. Clinical/sonographic characteristics predicting residual mass formation were maximal diameter of gestational sac (OR = 1.05, P = 0.001, with a sensitivity and specificity of 68.6 and 80.3%, respectively), presence of a fetal heart beat (OR = 2.63, P = 0.002, with a sensitivity and specificity of 62.9 and 67.2%, respectively), remnant myometrial thickness (OR = 108.91, P = 0.001 when thickness was less than 1 mm, with a sensitivity and specificity of 42.9% and 96.6%), location of gestational sac (OR = 59.20, P = 0.01 for complete type, with a sensitivity and specificity of 99.0 and 36.9%), and Doppler signal grading (OR = 8.08, P = 0.013 for Grade III, with a sensitivity and specificity of 83.8 and 51.0%).Conclusions: UACE followed by evacuation was effective for CSP and subsequent mixed mass formation could be predicted by some clinical/sonographic characteristics. [ABSTRACT FROM AUTHOR]

Study Question: Does second-hand smoke (SHS) exposure from husbands have adverse effects on sex hormones, metabolic profiles, clinical phenotypes and fertility outcomes in women with polycystic ovary syndrome (PCOS) undergoing ovulation induction?Summary Answer: SHS exposure is associated with worsened biochemical hyperandrogenism, higher incidence of metabolic syndrome and reduced conception rates in women with PCOS.What Is Known Already: Smoking in women impairs fecundity at some stages of the reproductive process including folliculogenesis, embryo transport, endometrial angiogenesis and uterine blood flow. Yet little is known about the hazard of SHS exposure in women with PCOS.Study Design, Size, Duration: This study was a secondary analysis of the Polycystic Ovary Syndrome Acupuncture and Clomiphene Trial (PCOSAct), a large randomized controlled trial conducted at 27 hospitals from 2012 to 2015 in mainland China.Participants/materials, Setting, Methods: Out of 1000 women with PCOS, SHS exposure status were available in 500 women, of whom 271 women were non-exposed and 229 exposed to cigarette smoke (170 women ≤10 cigarettes per day as low-SHS exposed and 59 women >10 cigarettes per day as high-SHS exposed). We compared circulating sex steroids, glucose and lipid metabolism, metabolic syndrome and phenotypes, fertility and obstetric outcomes between non-exposed and exposed women.Main Results and the Role Of Chance: Women exposed to SHS, compared to non-exposed women, had a higher serum total testosterone (1.7 vs 1.5 nmol/L, P = 0.01), free androgen index (5.7 vs 4.0, P = 0.001) and lower sex hormone binding globulin (30.1 vs 35.6 nmol/L, P = 0.03). Metabolic syndrome, but not other phenotypes, was more frequent in exposed women as compared to non-exposed women (21.8 vs 13.3%, adjusted odds ratio (OR)=1.66; 95% CI, 1.02-2.71, P = 0.04). Ovulation rates between exposed and non-exposed groups were not significantly different (76.9 vs 82.9%, adjusted OR=0.72; 95% CI, 0.45-1.15, P = 0.17). Conception rates were significant lower in the exposed group (26.6 vs 36.9%; adjusted OR=0.61; 95% CI, 0.41-0.91; P = 0.01), while clinical pregnancy and live birth rates showed a similar trend that was not statistically significant. Gestational age, birth weight and other obstetric outcomes were not affected by SHS exposure.Limitations, Reasons For Caution: Data on SHS exposure were missing in 50% of the women. We did not assay serum nicotine or cotinine levels to quantify the SHS exposure status.Wider Implications Of the Findings: These data suggest that smoking partners of infertile women with PCOS who seek treatment should be advised to quit smoking.Study Funding/competing Interest(s): Funding was provided by the National Public Welfare Projects for Chinese Medicine (201107005 and 200807002) and the National Clinical Trial Base in Chinese Medicine Special Projects (JDZX2012036 and 2015B009). There are no conflicts of interest.Trial Registration Number: ClinicalTrial.gov number: NCT01573858 and chictr.org.cn number: ChiCTR-TRC-12002081. [ABSTRACT FROM AUTHOR]

Objective: To compared the therapeutic effect of a Chinese patent medicine Naoxintong Capsule (脑心通胶囊, NXT) and aspirin with adjusted-dose warfarin in Chinese elderly patients (over 65 years) with nonvalvular atrial fibrillation (NVAF) and genetic variants of vitamin K epoxide reductase (VKORC1), who are at high-risk of thromboembolism.Methods: A total of 151 patients, with NVAF and AA genotype of VKORC1-1639 (a sensitive genotype to warfarin) and a CHA2DS2-VASc clinical risk score of 2 or above, were chosen for this study. Patients were randomized into two groups and orally treated with a combination of aspirin (100 mg/day) and NXT (1.6 g thrice a day) or adjusted-dose warfarin [international normalized ratio 2.0-3.0). The primary end points including ischemic stroke and death as well as the secondary end points including hemorrhage events were followed up for at least 1 year.Results: Baseline clinical data and the rates of primary end points were similar between groups. However, the rate of serious bleeding (secondary event) in the combination therapy group was lower than that in the adjusted-dose warfarin group (0% vs. 7.9%, odds ratio: 0.921, 95% confidence interval: 0.862-0.984, P=0.028).Conclusions: Aspirin combined with NXT and warfarin displayed comparable rates of primary end point including ischemic stroke and all-cause death during the 1-year follow-up. However, as compared with warfarin, the combination therapy reduced the rate of serious bleeding. Therefore, aspirin combined with NXT might provide an alternative pharmacotherapy in preventing ischemic stroke for elderly patients with NAVF who cannot tolerate warfarin. (No. ChiCTR-TRC-13003596) [ABSTRACT FROM AUTHOR]

Background: This study examined the prognostic significance of human papillomavirus (HPV) in patients with oropharyngeal and oral cavity squamous cell carcinoma (SCC).Methods: Tissue microarrays were constructed from oropharyngeal and oral cavity SCC (n = 143). The presence of functional HPV in tumour was determined by combined assessments of p16 immunohistochemistry and HPV in situ hybridisation.Results: Oropharyngeal SCC patients presented with more advanced disease in comparison with oral cavity SCC patients (P = 0.001). HPV is present in 60% and 61% of oropharyngeal and oral cavity SCC patients, respectively. HPV-positive oropharyngeal SCC patients with advanced TNM stages displayed better overall and disease-free survival outcomes than HPV-negative patients (P = 0.022 and 0.046, respectively). Such survival differences were not observed in oral cavity SCC.Conclusions: HPV is common in both oropharyngeal and oral cavity SCC and is associated with better survival outcome in oropharyngeal SCC but not in oral cavity SCC patients. [ABSTRACT FROM AUTHOR]

Background: Perimenopausal insomnia is one of the core symptoms of the menopausal transition. Acupuncture is considered to exert a positive effect on restoring the normal sleep-wake cycle. However, there is little intuitive evidence besides evaluation using clinical effectiveness scales. We therefore designed this study, aiming to use more intuitive and reliable detection techniques such as functional magnetic resonance imaging before and after applying acupuncture to provide neuroimaging evidence, as well as to verify the effectiveness with other curative effect indicators.Methods/design: This study is a randomized, assessor-statistician-blinded, positive medicine controlled trial involving 40 participants. A total of 40 eligible patients with perimenopausal insomnia will be randomly assigned to two groups in a 1:1 ratio as an intervention group using acupuncture and a control group taking estazolam. Participants in the intervention group will receive six acupuncture treatment sessions per week for 4 consecutive weeks, for a total of 24 sessions during the study. Meanwhile, the medicine control group will be prescribed estazolam 1-2 mg/day to be taken 30 minutes before sleep for 4 weeks. The primary outcome is the Pittsburgh Sleep Quality Index. Secondary outcomes are the micro-movement sensitive mattress-type sleep monitoring system, the Hamilton Depression Scale, and the Hamilton Anxiety Scale. All outcomes will be evaluated before and after treatment. The safety of interventions will be assessed at every visit.Discussion: The results of this trial, which will be available in 2018, will investigate the impact of acupuncture treating perimenopausal insomnia from assessment of the sleep architecture, hormone level, and emotional-circuit neurological function, and will uncover the effective mechanism of acupuncture regulating the emotional center integrated effect.Trial Registration: Chinese Clinical Trials Register, ChCTR-IPC-16007832 . Registered on 26 January 2016. [ABSTRACT FROM AUTHOR]

Background: Our study was aimed to explore the clinical implication of chromosome microarray analysis (CMA) in genetically etiological diagnosis of children with congenital heart disease (CHD).Methods: A total of 104 children with CHD with or without multiple congenital anomalies (MCA) or intellectual disabilities/developmental delay (ID/DD) but normal karyotype were investigated using Affymetrix CytoScan HD array.Result: Pathogenic copy number variations (PCNVs) were identified in 29 children (27.9%). The detection rates in children with simple CHD and complex CHD were 31.1% (19/61) and 23.2% (10/43), respectively. The detection rates of PCNVs were 17.9% (7/39), 20% (5/25), 63.2% (12/19) and 23.8% (5/21) in isolated CHD, CHD plus MCA, CHD plus ID/DD, CHD plus MCA and ID/DD, respectively. The PCNVs rate of CHD plus ID/DD was significantly higher than that of isolated CHD. Two genomic loci including 15q11.2 deletion and 1q43-q44 deletion were considered as CHD locus. The DVL1, SKI, STIM1, CTNNA3 and PLN were identified as candidate genes associated with CHD phenotypes.Conclusion: CMA can increase the diagnostic rate and improve the etiological diagnosis in children with CHD. We suggest CMA as a first-tier test in children with CHD, especially in children with CHD plus ID/DD. [ABSTRACT FROM AUTHOR]

BACKGROUND The genus Monascus includes several species of fungi valued across Asia for their culinary uses and diverse medicinal properties. In this study, we evaluated the applicability of random amplified polymorphic DNA ( RAPD) and inter-simple sequence repeats ( ISSR) markers in characterizing the genetic diversity in 41 Monascus strains collected from various regions of Fujian Province, the leading producer of Monascus in China. RESULTS Seven screened ISSR primers generated 56 polymorphic bands, of which 93.33% were polymorphic. The genetic similarity coefficients ( GSC) of the strains ranged from 0.50 to 1.00. Comparative sequence analysis using seven screened RAPD primers amplified a total of 49 polymorphic bands, of which 81.67% were polymorphic; GSC values ranged from 0.62 to 1.00. CONCLUSION Correlation analysis revealed a significant positive correlation in genetic distances assessed using above two markers, which indicated they were suitable for Monascus species characterization. ISSR markers were more suitable for the classification and determination of Monascus species, while RAPD markers appear to be preferable for analyzing the differences among strains within the same species. Our study revealed that Monascus possesses rich genetic diversity, and that the genetic relationships among the selected strains were, to a very limited extent, correlated to their geographical variation. © 2016 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Background: A survival paradox between Stage IIB/C and Stage IIIA colon cancers exists. It is unclear how adequate lymph nodes dissection (LN) and post-surgery chemotherapy contribute to the survival paradox. We intended to assess the impact of these two factors on the survival paradox.Results: We evaluated 34,999 patients diagnosed with stage IIIA or stage IIB/C colon cancer in 2003-2012 from the National Cancer Data Base. The 5-year overall survival (OS) was 73.5 % for stage IIIA and 51.1 % for stage IIB/C (P < 0.0001). The 5-year OS was 84.1 % for stage IIIA with post-surgery chemotherapy, 70.8 % for stage IIB/C with ≥ 12 LNs retrieved with chemotherapy, 53.9 % for stage IIB/C < 12 LNs with chemotherapy, 49.5 % for stage IIIA without chemotherapy, 43.7 % for stage IIB/C ≥ 12 LNs retrieved without chemotherapy, to 27.7 % for stage IIB/C < 12 LNs without chemotherapy. Even among stage IIB/C who had optimal treatment (≥12 LNs retrieved, received chemotherapy), OS remains lower than stage IIIA with chemotherapy. After adjusting LN dissection and chemotherapy in addition to the adjustment of other clinical factors, the survival paradox was reduced from HR = 1.76 (95 % CI: 1.68-1.85) to HR 1.51 (95 % CI: 1.44-1.59).Conclusions: LN dissection and post-surgery chemotherapy partially explained the survival paradox. More research is warranted to identify other factors that contribute to this paradox. Future iteration of TNM staging system should take this into consideration. [ABSTRACT FROM AUTHOR]

Growth in sucrose medium was previously found to trigger the expression of functions involved in the plant associated life style of the endophytic bacterium Enterobacter sp. 638. Therefore, comparative transcriptome analysis between cultures grown in sucrose or lactate medium was used to gain insights in the expression levels of bacterial functions involved in the endophytic life style of strain 638. Growth on sucrose as a carbon source resulted in major changes in cell physiology, including a shift from a planktonic life style to the formation of bacterial aggregates. This shift was accompanied by a decrease in transcription of genes involved in motility (e.g. flagella biosynthesis) and an increase in the transcription of genes involved in colonization, adhesion and biofilm formation. The transcription levels of functions previously suggested as being involved in endophytic behavior and functions responsible for plant growth promoting properties, including the synthesis of indole-acetic acid, acetoin and 2,3-butanediol, also increased significantly for cultures grown in sucrose medium. Interestingly, despite an abundance of essential nutrients transcription levels of functions related to uptake and processing of nitrogen and iron became increased for cultures grown on sucrose as sole carbon source. Transcriptome data were also used to analyze putative regulatory relationships. In addition to the small RNA csrABCD regulon, which seems to play a role in the physiological adaptation and possibly the shift between free-living and plant-associated endophytic life style of Enterobacter sp. 638, our results also pointed to the involvement of rcsAB in controlling responses by Enterobacter sp. 638 to a plant-associated life style. Targeted mutagenesis was used to confirm this role and showed that compared to wild-type Enterobacter sp. 638 a ΔrcsB mutant was affected in its plant growth promoting ability. [ABSTRACT FROM AUTHOR]

Aims: To assess the clinical significance and risk factors of solitary lymph node metastasis (SLM) in gastric carcinoma and establish a more accurate method to evaluate the possibility of lymph node metastasis (LM). Methods: A total of 385 patients with gastric carcinoma who underwent D2 lymphadenectomy at the Cancer Center of Sun Yat-Sen University were included in this research. Then we used a group of data from Sun Yat-sen University Gastrointestinal Hospital (SYSUGIH) to validate the accuracy of our developed method. The χ2 test, Kaplan–Meier analysis, log-rank test, COX model, and discriminate analysis were used to analyze the data with SPSS13.0. Results: We found that the LM number and pathological T staging were independent prognostic risk factors. CEA grading, LN status by CT, and T staging by CT were independent risk factors for LM in gastric carcinoma. In addition, we developed the equation Y = -5.0 + X1 + 1.8X3 + 0.7X4 (X1 = CEA grading, X3 = LN status by CT, X4 = T staging by CT) to evaluate the situation of LM. The data from SYSUGIH shows this equation has a better accuracy compared with CT. Conclusions: SLM is an independent risk factor in gastric cancer. And there was no survival difference between the skip metastasis group and the other SLM group (P = 0.659). It is inappropriate for the patient with SLM doing a standard D2 lymphadenectomy, due to the fact that LM rarely occurs in the splenic artery, splenic hilum. The risk factors for LM include CEA grading, LN status by CT, and T staging by CT. And we can use Y = -5.0 + X1 + 1.8X3 + 0.7X4 (X1, CEA grading, X3 = LN status by CT, X4 = T staging by CT, the critical value is 0.3) to estimate the possibility of LM, which has a better accuracy compared with CT. [ABSTRACT FROM AUTHOR]

Human adenovirus type 55 (HAdV-B55) represents a re-emerging human pathogen, and this adenovirus has been reported to cause outbreaks of acute respiratory diseases among military trainees and in school populations around the world. HAdV-B55 has been revealed to have evolved from homologous recombination between human adenovirus type 14 (HAdV-B14) and type 11 (HAdV-B11), but it presents different clinical manifestations from parental virus HAdV-B11. In the present paper, we report the distinct biological features of HAdV-B55 in comparison with the parental viruses HAdV-B11 and HAdV-B14 in cell cultures. The results showed that HAdV-B55 replicated well in various cells, similar to HAdV-B11 and HAdV-B14, but that its processing had a slower and milder cytopathic effect in the early stages of infection. Viral fitness analysis showed that HAdV-B55 exhibited higher levels of replication in respiratory cells than did either of its parents. Cytotoxicity and apoptosis analyses in A549 cells indicated that HAdV-B55 was less cytotoxic than HAdV-B11 and HAdV-B14 were and induced milder apoptosis. Finally, thermal sensitivity analysis revealed that HAdV-B55 exhibited lower thermostability than did either HAdV-B11 or HAdV-B14, which may limit the transmission of HAdV-B55 in humans. Together, the findings described here expand current knowledge about this re-emerging recombinant HAdV, shedding light on the pathogenesis of HAdV-B55. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical effectiveness of dutasteride in the treatment of benign prostatic hyperplasia by meta-analysis. Materials and Methods: Several databases were searched from inception to June 2013 for prospective clinical studies comparing dutasteride vs placebo. The continuous outcomes of therapeutic efficacy included International Prostate Symptom Score/American Urological Association Symptom Index, maximum flow rate, total prostate volume, and acute urinary retention (AUR). The dichotomous outcomes included surgery risk and the rate of sexual dysfunction. The relative risk for dichotomous outcome and the weighted mean difference for continuous outcomes were estimated using fixed effects model. Results: Four studies met the inclusion criteria and were included, in which a total of 6460 patients received dutasteride and 6475 received placebo treatment. The average symptom score was improved by 1.98 with 95% confidence interval (CI) 1.77-2.19 (P <.00001); the average maximum flow rate was increased by 1.16 mL/s with 95% CI 0.63-1.70 (P <.0001); the total prostate volume was reduced by 13.86 mL (95% CI 12.76-14.96; P <.00001); the odds ratio for AUR was 0.35 (95% CI 0.27-0.47; P <.00001). The major side effect for dutasteride was the increased rate of sexual dysfunction compared with placebo, with odds ratio of 0.41 (95% CI 0.31-0.54; P <.00001). Conclusion: Dutasteride is highly effective in mitigating benign prostatic hyperplasia symptoms and reducing the size of enlarged prostate and the risks of AUR and surgical intervention. However, dutasteride therapy is related to an increased rate of sexual dysfunction. [Copyright &y& Elsevier]

Background: Culture-independent phylogenetic analysis of 16S ribosomal RNA (rRNA) gene sequences has emerged as an incisive method of profiling bacteria present in a specimen. Currently, multiple techniques are available to enumerate the abundance of bacterial taxa in specimens, including the Sanger sequencing, the 'next generation' pyrosequencing, microarrays, quantitative PCR, and the rapidly emerging, third generation sequencing, and fourth generation sequencing methods. An efficient statistical tool is in urgent need for the followings tasks: (1) to compare the agreement between these measurement platforms, (2) to select the most reliable platform(s), and (3) to combine different platforms of complementary strengths, for a unified analysis. Results: We present the latent variable structural equation modeling (SEM) as a novel statistical application for the comparative analysis of measurement platforms. The latent variable SEM model treats the true (unknown) relative frequency of a given bacterial taxon in a specimen as the latent (unobserved) variable and estimates the reliabilities of, and similarities between, different measurement platforms, and subsequently weighs those measurements optimally for a unified analysis of the microbiome composition. The latent variable SEM contains the repeated measures ANOVA (both the univariate and the multivariate models) as special cases and, as a more general and realistic modeling approach, yields superior goodness-of-fit and more reliable analysis results, as demonstrated by a microbiome study of the human inflammatory bowel diseases. Conclusions: Given the rapid evolution of modern biotechnologies, the measurement platform comparison, selection and combination tasks are here to stay and to grow - and the latent variable SEM method is readily applicable to any other biological settings, aside from the microbiome study presented here. [ABSTRACT FROM AUTHOR]

The first copper-catalyzed trifluoromethylation of aryl halides was developed that utilizes inexpensive trifluoroacetates. Providing low concentrations of the most economically attractive and atom-efficient trifluoromethylation reagent this new protocol is advantageous compared to known procedures both economically and ecologically. [ABSTRACT FROM AUTHOR]

Abstract: Somatostatin (SRIF), as a neuroactive peptide in the CNS, may act as a neuromodulator through activation of five specific receptor subtypes (sst1–sst5). In this work we conducted a comparative study of the expression of sst5 in mouse and bullfrog retinas by immunofluorescence double labeling. Basically, the expression profiles of sst5 in the retinas of the two species were similar. That is, in the inner retina sst5 was localized to dopaminergic and cholinergic amacrine cells, stained by tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) respectively, and cells in the ganglion cell layer, whereas in the outer retina immunostaining for sst5 was observed in horizontal cells. However, a more widespread, abundant distribution of labeling for sst5, as compared to mouse retina, was seen in bullfrog retina: strong labeling for sst5 was diffusely distributed in both outer and inner plexiform layers (OPL and IPL) in the bullfrog retina, but the labeling was only observed in the IPL of the mouse retina. In addition, bullfrog photoreceptors, both rods and cones, but not mouse ones, were labeled by sst5. In combination with the experiments showing that SRIF-immunoreactivity was mainly found in the inner retina, our results suggest that SRIF, released from SRIF-containing cells in the inner retina, may play a neuromodulatory role in both outer and inner retina mediated by volume transmission via sst5 in bullfrog retina, while the SRIF action may be largely restricted to the mouse inner retina. [Copyright &y& Elsevier]

We evaluated cancer risk with three VEGF polymorphisms (-460C>T, -2578C>A, 1612G>A) based on current available studies. -460C>T did not appear to influence cancer risks. -2578C carriers had a 30%% reduction of colorectal cancer (CRC) risk in comparison with AA homozygote (OR: 0.70, CI: 0.56--0.88). 1612G carriers had a striking 84%% reduction of gastric cancer risk in comparison with AA homozygote. Multiple pair-wise comparisons suggested a recessive role for both -2578A and 1612A risk allele. Further studies with larger samples, well-matched controls and homogenous ethnic background are warranted to confirm these findings. We recommend more efforts into the investigation of 1612G>A with cancer risks. [ABSTRACT FROM AUTHOR]

The aim of this paper was to evaluate an improved buffy coat (BC) method of Compomat G4 for automated expression of BCs twice from whole blood (WB) in top and top (T&T) bags. WB was separated using hard spin centrifugation (2,988g, 10 min) into layers of blood components by specific gravity, and different components were subsequently expressed into satellite bags in the T&T system using the manual BC method, the conventional BC method of G4, and our improved BC method of G4. In the improved BC method, an accessorial device we have named a 'gravity press' was designed and installed on the top flat of G4 to produce gravitational pressure on the plasma bag so as to exclude air and some of plasma to the upper compartment of the slide after BCs were expressed for the first time. The residual BCs in the upper compartment were expressed a second time by extending the upper press once more. All of the pooled BCs were centrifuged by soft spin (402g, 10 min) and upper platelet-rich supernatant was manually expressed into a platelet container by the plasma extractor. In vitro studies of blood components and pooled platelet concentrates (PCs) revealed no significant differences in BC blood components and platelet recovery of pooled platelets (61 ± 9 vs. 60 ± 7%, n = 12, p > 0.05) between the improved BC method and the conventional BC method; all components met our specifications for blood products. We suggest that the new BC method for use of T&T bags may improve the collection of BCs. [ABSTRACT FROM AUTHOR]

Pseudomonas putida is a gram-negative rod-shaped gammaproteobacterium that is found throughout various environments. Members of the species P. putida show a diverse spectrum of metabolic activities, which is indicative of their adaptation to various niches, which includes the ability to live in soils and sediments contaminated with high concentrations of heavy metals and organic contaminants. Pseudomonas putida strains are also found as plant growth-promoting rhizospheric and endophytic bacteria. The genome sequences of several P. putida species have become available and provide a unique tool to study the specific niche adaptation of the various P. putida strains. In this review, we compare the genomes of four P. putida strains: the rhizospheric strain KT2440, the endophytic strain W619, the aromatic hydrocarbon-degrading strain F1 and the manganese-oxidizing strain GB-1. Comparative genomics provided a powerful tool to gain new insights into the adaptation of P. putida to specific lifestyles and environmental niches, and clearly demonstrated that horizontal gene transfer played a key role in this adaptation process, as many of the niche-specific functions were found to be encoded on clearly defined genomic islands. [ABSTRACT FROM AUTHOR]

The braincase of a polycotylid plesiosaur referable to Dolichorhynchops from the Niobrara Formation (Santonian to the earliest Campanian) in Manitoba, Canada, is described. The well-preserved material without matrix permits observation of various anatomical features of the polycotylid braincase with unprecedented clarity. A virtual reconstruction of the braincase was created by using a three-dimensional scanning technique that produces accurate reconstruction of missing or damaged elements and demonstrates the three-dimensional relationships among the elements. Comparison with other plesiosaurian braincases revealed previously unrecognized characters and character states. The I-beam-shaped parasphenoid, the relatively short pituitary fossa, and the anterior process of the prootic are possible synapomorphies of the Polycotylidae or of its subclades. It could be a challenge to confirm the presence of the supraoccipital process and its median ridge, as well as the presence of the fenestra ovalis, in polycotylid skulls because of the location and orientation of these structures. Variable morphology of basioccipital-basisphenoid contact and the paroccipital process in Dolichorhynchops and related taxa require further investigation. The I-beam of the parasphenoid and the wide contact surfaces of the basioccipital and neighboring elements provide more resistance to flexion of the braincase. Distribution of the extensive pterygoid-basicranium contact, the shape of foramen magnum, anterior process of the prootic, and the short pituitary fossa do not confirm the current phylogenetic hypotheses. The location and orientation of the fenestra ovalis suggest the lack of a tympanic ear in this plesiosaur. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the cross cultural validity and reliability of the Chinese Language version of the Eating Disorder Examination (CEDE) in Wuhan, China, and to examine the psychopathogical profile of eating disorder patients in central Mainland China. Participants and Method: We administered the CEDE to 41 eating disorder patients (anorexia nervosa and bulimia nervosa) with 43 noneating disorder controls. Specialists in eating disorders made the clinical diagnosis according to DSMIV criteria. CEDE data between the two groups were compared. Results: The CEDE demonstrates good internal consistency, test-retest reliability, and inter-examiner reliability. All CL-EDE subscales discriminated between patients with anorexia nervosa or bulimia nervosa from non-eating disordered controls. The CEDE has satisfactory sensitivity, specificity, and positive and negative predictive values. Discussion: The CEDE is a useful instrument for the study of the growing clinical problem of the eating disorders in Mainland China. The finding that the characteristic fat phobia is prominent in this population of eating disordered patients and its implication on the identity and classification of the eating disorders are discussed. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to identify risk factors of lymph node metastasis (LNM) for T2 rectal cancer.Methods: From a prospectively maintained single-institution database, we identified 346 consecutive pT2 rectal cancers treated with total mesorectal excision from 1998 to 2009. Univariate and multivariate analyses were performed to identify risk factors associated with overall and intermediate/apical LNM. The incidence of overall and intermediate/apical LNM was analyzed by tree analysis.Results: Age, tumor location, pathological features, and depth of invasion were independent predictors for overall LNM. Tumor location, pathological features, and depth of invasion were independent predictors for intermediate/apical LNM. Tree analysis showed that the incidence of LNM was 7.7% for upper rectal cancer with favorable pathological features, and 3.4% for mid/lower rectal cancer without other identified risk factors. The incidence of intermediate/apical LNM was 5.7% for superficial T2 rectal cancer with favorable pathological features, and 3.1% for deep T2 rectal cancer locating in upper rectum with favorable pathological features.Conclusions: Depth of invasion is an independent predictor for LNM in T2 rectal cancer. Using tree analysis, we identified a subset of patients with low risk of LNM who may be candidates of local excision. [ABSTRACT FROM AUTHOR]

Abstract: The non-quenched prehardened (NQP) steel and quenched and tempered prehardened (QP) steel for plastic mould were compared in terms of their microstructures, machinability, hardness and weldability along with their continuous cooling transformation. Results show that the microstructure of the NQP steel bloom consists of bainite through the whole section, while tempered martensite and bainite are found across the whole section of the QP steel. However, hardness fluctuations of two types of steel are not more than 3 HRC, for the former contributed to the high bainitic hardenability, while, for the latter, microstructures were adjusted by heat treatment after forging. Compared with the QP steel, the NQP steel results in better machinability, weldability and requires a simplified process that saves energy. [Copyright &y& Elsevier]

Studies investigating the association of polymorphisms in the 5'-untranslated regions (5'UTR) and 3'-untranslated regions (3'UTR) of thymidylate synthase with gastric cancer susceptibility and sensitivity to fluoropyrimidine-based chemotherapy report conflicting results. The objective of this study was to quantitatively summarize the evidence for such a relationship. This meta-analysis included ten studies, which included 1,730 gastric cancer cases and 1,843 controls. The combined results based on all studies showed that there was no significant difference in genotype distribution of 5'UTR or 3'UTR between gastric cancer and noncancer patients. When stratifying for race, we found that: (1) among Asians, patients with gastric cancer had significantly higher frequency of 2R/2R of 5'UTR than did noncancer patients, and (2) among Caucasians, patients with gastric cancer had significantly lower frequency of ins6/ins6 and higher frequency of ins6/del6 of 3'UTR than did noncancer patients. No significantly different response rate or survival of gastric cancer with fluoropyrimidine-based chemotherapy were observed with genotype distribution of 5'UTR or 3'UTR among Caucasians or Asians. This meta-analysis suggests that polymorphisms in the 5'UTR and 3'UTR of thymidylate synthase may be associated with gastric cancer susceptibility, but are not correlated with sensitivity of gastric cancer to fluoropyrimidine-based chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Walking is a simple but beneficial form of physical activity (PA). Self-monitoring and providing information about social norms are the 2 most widely used "mobile health (mHealth)" strategies to promote walking behavior. However, previous studies have failed to discriminate the effect of self-monitoring from the combination of the 2 strategies, and provide practical evidence within Chinese culture. Some essential moderators, such as gender and group identity, were also overlooked.Objective: We aimed to investigate the effectiveness of social norm and self-monitoring interventions for walking behavior and assess the moderating effects of gender and group identity, which could guide optimal mHealth intervention projects in China.Methods: In 2 longitudinal tracking studies (study 1, 22 days; study 2, 31 days), Chinese college students wore trackers for at least 8 hours per day (MASAI 3D Pedometer and Xiaomi Wristband 2) to record their daily step counts in baseline, intervention, and follow-up stages. In each study, participants (study 1: n=117, 54% female, mean age 25.60 years; study 2: n=180, 51% female, mean age 22.60 years) were randomly allocated to 1 of the following 3 groups: a self-monitoring group and 2 social norm intervention groups. In the 2 intervention groups and during the intervention stage, participants received different social norm information regarding group member step rankings corresponding to their grouping type of social norm information. In study 1, participants were grouped by within-group member PA levels (PA consistent vs PA inconsistent), and in study 2, participants were grouped by their received gender-specific social norm information (gender consistent vs gender inconsistent). Piece-wise linear mixed models were used to compare the difference in walking steps between groups.Results: In study 1, for males in the self-monitoring group, walking steps significantly decreased from the baseline stage to the intervention stage (change in slope=-1422.16; P=.02). However, additional social norm information regardless of group consistency kept their walking unchanged. For females, social norm information did not provide any extra benefit beyond self-monitoring. Females exposed to PA-inconsistent social norm information even walked less (slope during the intervention=-122.18; P=.03). In study 2, for males, a similar pattern was observed, with a decrease in walking steps in the self-monitoring group (change in slope=-151.33; P=.08), but there was no decrease in the 2 social norm intervention groups. However, for females, gender-consistent social norm information decreased walking steps (slope during the intervention=-143.68; P=.03).Conclusions: Both gender and group identity moderated the effect of social norm information on walking. Among females, social norm information showed no benefit for walking behavior and may have exerted a backfire effect. Among males, while walking behavior decreased with self-monitoring only, the inclusion of social norm information held the level of walking behavior steady. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the mechanism of interferon alpha (IFN-α) on inhibition of metastasis and recurrence of hepatocellular carcinoma (HCC). Nude mice bearing human HCC xenografts with high metastatic potential (LCI-D20) underwent curative resection of tumors on postimplant day 11. IFN-α was begun the next day at different dosages given subcutaneously for 35 consecutive days; normal saline solution was injected into the control mice. The mice were killed 48 hours after the final treatment, and the parameters were evaluated. The HCC intrahepatic recurrence rate, the size of the recurrent lesions, the rate of lung metastasis, the serum vascular endothelial growth factor level, and the microvessel density (immunohistochemistry) were as follows: 100%, 2136±794 mm3(mean±standard deviation), 100%, 265.7±154.7 pg/ml, and 144±37/HP, respectively, in the control mice, whereas these same values were 62.5%, 89±45 mm3, 12.5%, 53.3±9.9 pg/ml, and 86±25/HP, respectively, in the IFN-α 1.5×107U/kg treatment group (P<0.05) and 26.7%, 46±21 mm3, 0%, 65.2±17.9 pg/ml, and 39±14/HP in the IFN-α 3×107U/kg treatment group, respectively (P<0.05). However, a significant difference was not found in the serum levels of basic fibroblast growth factor among the control and IFN-α treatment groups. IFN-α inhibits metastasis and recurrence of human HCC after curative resection in nude mice mediated by antiangiogenesis through downregulating expression of vascular endothelial growth factor but not basic fibroblast growth factor. [Copyright &y& Elsevier]