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The phenomenon of delta inflation, in which design treatment effects tend to exceed observed treatment effects, has been documented in several therapeutic areas. Delta inflation has often been attributed to investigators' optimism bias, or an unwarranted belief in the efficacy of new treatments. In contrast, we argue that delta inflation may be a natural consequence of clinical equipoise, that is, genuine uncertainty about the relative benefits of treatments before a trial is initiated. We review alternative methodologies that can offer more direct evidence about investigators' beliefs, including Bayesian priors and forecasting analysis. The available evidence for optimism bias appears to be mixed, and can be assessed only where uncertainty is expressed explicitly at the trial design stage., (© 2024. The Author(s), under exclusive licence to The Drug Information Association, Inc.)

Background: The optimal treatment for esophageal squamous cell carcinoma (ESCC) patients with postoperative recurrence remains controversial. We aimed to evaluate the effects of radiotherapy (RT) and chemoradiotherapy (CRT) on postoperative recurrence in ESCC patients., Methods: Recurrence ESCC patients who received salvage RT and CRT from January 2015 to January 2019 were retrospectively reviewed. Post-recurrence survival (PRS) and prognostic factors were evaluated by Kaplan-Meier and Cox proportional hazards models, respectively. Subgroup analyses were performed based on pathological lymph node (LN) status (negative/positive) to evaluate the differences in salvage treatments and toxic reaction., Results: A total of 170 patients were enrolled, with a median age of 60 years (range 43-77). No significant difference was found in the median PRS between the salvage RT and CRT groups (p > 0.05). Multivariate analysis revealed that TNM stage III and IV, macroscopic medullary type, and distant metastasis recurrence pattern were independent prognostic factors (all p < 0.05) for PRS. Salvage treatment was not associated with PRS (p = 0.897). However, in patients with negative LN, CRT was associated with prolonged survival (p = 0.043) and had no significant differences in toxic reactions compared to RT (p = 0.924). In addition, RT showed better prognoses (p = 0.020) and lower toxic reactions (p = 0.030) than CRT in patients with positive LNs., Conclusions: Based on prognosis and toxic reactions, ESCC recurrence patients with negative LNs could benefit from CRT, but RT should be recommended for patients with positive LNs., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

As an alternative to the Frequentist p-value, the Bayes factor (or ratio of marginal likelihoods) has been regarded as one of the primary tools for Bayesian hypothesis testing. In recent years, several researchers have begun to re-analyze results from prominent medical journals, as well as from trials for FDA-approved drugs, to show that Bayes factors often give divergent conclusions from those of p-values. In this paper, we investigate the claim that Bayes factors are straightforward to interpret as directly quantifying the relative strength of evidence. In particular, we show that for nested hypotheses with consistent priors, the Bayes factor for the null over the alternative hypothesis is the posterior mean of the likelihood ratio. By re-analyzing 39 results previously published in the New England Journal of Medicine, we demonstrate how the posterior distribution of the likelihood ratio can be computed and visualized, providing useful information beyond the posterior mean alone., (© 2024 John Wiley & Sons Ltd.)

Bayesian predictive probabilities have become a ubiquitous tool for design and monitoring of clinical trials. The typical procedure is to average predictive probabilities over the prior or posterior distributions. In this paper, we highlight the limitations of relying solely on averaging, and propose the reporting of intervals or quantiles for the predictive probabilities. These intervals formalize the intuition that uncertainty decreases with more information. We present four different applications (Phase 1 dose escalation, early stopping for futility, sample size re-estimation, and assurance/probability of success) to demonstrate the practicality and generality of the proposed approach.

Background: The site of lymph node metastasis (LNM) may affect the prognosis of patients with esophageal squamous cell carcinoma (ESCC). To investigate the prognoses of pararespiratory and paradigestive LNM and to propose a novel N (nN) staging system that integrates both the LNM site and count., Methods: This study was a multicenter, large-sample, retrospective cohort study that included ESCC patients with LNM between January 2014 and December 2019 from three Chinese institutes. Patients were set into training (two institutes) and external validation (one institute) cohorts. The primary outcomes were survival differences in LNM site and the development of novel nodal staging system. The overall survival (OS) of patients with pararespiratory LNM only (Group A), paradigestive LNM only (Group B), and both sites (Group C) was evaluated by Kaplan-Meier. Cox proportional hazards models were used to identify the independent prognostic factors. An nN staging system considering both the LNM site and count was developed and evaluated by the area under the receiver operating characteristic curve (AUC)., Results: In total, 1313 patients were included and split into training (n = 1033) and external validation (n = 280) cohorts. There were 342 (26.0%), 568 (43.3%) and 403 (30.7%) patients in groups A, B and C, respectively. The OS of patients with pararespiratory and patients with paradigestive LNM presented significant differences in the training and validation cohorts (P < 0.050). In the training cohort, LNM site was an independent prognostic factor (hazard ratio: 1.58, 95% confidence intervals: 1.41-1.77, P < 0.001). The nN staging definition: nN1 (1-2 positive pararespiratory/paradigestive LNs), nN2 (3-6 pararespiratory LNs or 1 pararespiratory with 1paradigestive LN), nN3 (3-6 LNs with ≥ 1 paradigestive LN), nN4 (≥ 7 LNs). Subsets of patients with different nN stages showed significant differences in OS (P < 0.050). The prognostic model of the nN staging system presented higher performance in the training and validation cohorts at 3-year OS (AUC, 0.725 and 0.751, respectively) and 5-year OS (AUC, 0.740 and 0.793, respectively) than the current N staging systems., Conclusions: Compared to pararespiratory LNM, the presence of paradigestive LNM is associated with worse OS. The nN staging system revealed superior prognostic ability than current N staging systems., (© 2023. The Author(s).)

Melasma is a common hyperpigmented skin condition that occurs on the face and other areas prone to light exposure, seriously affecting people's quality of life. Microneedle, a new type of transdermal drug delivery device, can significantly improve skin permeability. In this study, we designed and fabricated a polymer microneedle roller (PMR) using a mold hot pressing method, and established a mouse model of melasma induced by ultraviolet radiation. The dynamometer and insertion test of MNs into parafilm and skin of mice indicates that the MNs have sufficient mechanical properties to insert parafilm and skin of mice. The two methods (apply hydroquinone cream (HQC) directly and pre-treat with PMR before applying HQC) were used to treat melasma. From the results of skin surface observation, determination of superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in skin and liver tissues, histological observation, and skin Optical coherence tomography (OCT), we confirmed both the two methods had a therapeutic effect while the PMR pretreatment group exhibited a better therapeutic effect. In addition, there were statistical differences between the UV group (P < 0.05). Together these results indicated that the MNs may be promising in future clinical applications in improving the UV irradiation-induced pigmentation like melisma., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Due to a recent development of high-frequency ultrasound (HFUS) systems, it is easier to realize high-resolution in vivo imaging of the biological tissues. The object of this study was to map the thickness and echo density of skin layers in healthy Chinese people and assess the influence of gender, age, and region on it., Methods: A total of 189 volunteers (85 male, 104 female) with age range of 22-75-year old (mean age of 41.2-year old) were enrolled. The thickness and density of the epidermis and dermis layer were detected by high-frequency (22 or 75 MHz) ultrasonography at 13 different anatomical sites, including the forehead, cheeks, flexor and extensor forearms, flexor and extensor upper arms, inner and outer legs, inner and outer thighs, back, and abdomen., Results: The thickness and density of epidermis/dermis between different anatomical sites were statistically significant (p < 0.05). The epidermis thickness of the face and trunk were less than that of the limbs, whereas the thicknesses of the dermis were on the contrary. The density of the epidermis/dermis of the face and trunk were less than that of the limbs. The thickness of dermis in most of the sites were higher in male than in female, and the density of epidermis and dermis in most of the sites were less in men than in women. The thicknesses/densities of dermis were lower in older age group in almost all sites, whereas only several sites reached statistical. The difference between the north and south regions showed the environment also influenced the thickness and density of the skin., Conclusion: HFUS provides a simple noninvasive method for evaluating the skin thickness and echo-density, which, reflecting intradermal structure, exhibit systematic regional variation. With the establishment of Chinese phenotypic database of skin thickness and density, it will be helpful for the skin disease assessment, skin surgery, and cosmetology technology., (© 2022 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Relationship between plant community functional diversity and ecosystem multifunctionality (EMF) was a new area of ecological research in recent years. Previous studies had mostly focused on the relationship between plant community functional diversity and individual ecosystem function, and lack of understanding of the EMF. In this study, six functional indices of aboveground biomass, soil organic carbon, soil total nitrogen, soil total phosphorus, soil available nitrogen and soil available phosphorus of Gannan alpine meadow were selected to analyze the relationship between plant community functional diversity and EMF on the altitude gradient of Gannan alpine mea-dow by using Bartlett sphericity test and multi-threshold method. The results showed that there was significant altitudinal difference in plant community composition, with species richness and plant coverage at 3500 m were significantly higher than those at other altitudes. Single and multi-functional diversity decreased with the increases of altitude, with significant difference among altitudes. Redundancy analysis showed that single and multi-functional richness, functional evenness and Rao's quadratic entropy were significantly positively correlated with soil temperature, soil water content and soil bulk density, and significantly negatively correlated with soil pH and soil conductivity. In a large threshold range (6%-89%), functional diversity had a significant positive effect on EMF. Based on correlation analysis, optimal regression model and random forest model, it was found that multi-functional richness index had a significant positive relationship with EMF, and that multi-functional richness was also the main driving factor of EMF. Overall, functional richness had the most significant impact on the EMF of alpine meadow in the Qinghai-Tibet Plateau.

Background: Recurrent laryngeal nerve (RLN) lymph node metastasis (LNM) is not rare in patients with esophageal squamous cell carcinoma (ESCC). We aimed to develop and externally validate a preoperative nomogram using clinical characteristics to predict RLN LNM in patients with ESCC and evaluate its prognostic value., Methods: A total of 430 patients with ESCC who underwent esophagectomy with lymphadenectomy of RLN LNs at two centers between May 2015 and June 2019 were reviewed and divided into training (center 1, n = 283) and external validation cohorts (center 2, n = 147). Independent risk factors for RLN LNM were determined by multivariate logistic regression, and a nomogram was developed. The performance of the nomogram was assessed in terms of discrimination, calibration, clinical usefulness, and prognostic value. The nomogram was internally validated by the bootstrap method and externally validated by the external validation cohort., Results: Multivariate analysis indicated that clinical T stage ( P <0.001), endoscopic tumor length ( P = 0.003), bioptic tumor differentiation ( P = 0.004), and preoperative carcinoembryonic antigen level ( P = 0.001) were significantly associated with RLN LNM. The nomogram had good discrimination with the area under the curve of 0.770 and 0.832 after internal and external validations. The calibration curves and decision curve analysis confirmed the good calibration and clinical usefulness of this model. High-risk of RLN LNM predicted by the nomogram was associated with worse overall survival in the external validation cohort ( P <0.001)., Conclusion: A nomogram developed by preoperative clinical characteristics demonstrated a good performance to predict RLN LNM and prognosis for patients with ESCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yan, Mao, Yu, Jiang, Huang, Zong, Qian, Guo, Wen and Tian.)

Developmental dysplasia of the hip (DDH) is a musculoskeletal condition occupying any point along a spectrum of anatomical abnormalities that alter the stability of the newborn hip. Presentation varies throughout infancy and the majority of cases, especially those that are mild in nature, tend to resolve without intervention. An analysis of outcomes was conducted on infants born over a two-year period at a single-center, community hospital in East Toronto. The unwritten norm at the institution has become to order hip ultrasonography for all infants born in the breech position through C-section. Given the healthcare expenditure associated with routine radiographic screening, a careful analysis was undertaken to ascertain whether this screening regimen was effective in preventing late-stage detection of advanced DDH and improving organization in patient management. There were a total of 4236 babies delivered over the two years. One-hundred sixty-four (164) babies were born breech and through C-section. Eight (8) babies had abnormal hip examinations, one of whom was ultimately diagnosed with DDH. Forty-six (46) babies showed abnormal hip ultrasound at six weeks. Seventeen (17) referrals were made to the orthopedic surgeon. This resulted in a total of seven cases of DDH being diagnosed over the two years. The sensitivity and specificity of clinical hip screening were 14.3% and 95.5%, respectively, while that for ultrasound screening was 100% and 75.2%. To improve the quality of care and detection of DDH, a risk factor analysis was conducted to retrospectively analyze which DDH cases would have been missed if a higher threshold to ordering hip ultrasonography had been used. Based on the test characteristics of clinical and ultrasonographic screening, held in conjunction with the risk factor analysis results, an altered screening regimen was proposed with the intention of being just as sensitive but more cost-effective. This regimen integrates clinical screening using Barlow and Ortalani maneuvers until the eight to 10-week period and examines for limited abduction from eight weeks onward. Adjuncts like the Galeazzi test and that for asymmetrical skin folds should also be included to increase the sensitivity of clinical screening. Ultrasonography is proposed for high-risk individuals, with the criteria for stratification as high-risk being extracted from the risk factor analysis. Ultrasound is also proposed to be done in a serial fashion prior to orthopedic surgery referral in cases where the age of the infant allows, which serves to better evaluate the risk for lasting DDH and understand the longitudinal trajectory of the patient. This serves the additional purpose of decreasing the psychosocial burden on families. This can be particularly significant for infants for whom the initial abnormalities are due to self-resolve with the maturation of the hip joint and the infant's growth., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Yu et al.)

Air quality has gradually improved in many parts of China; however, air pollution is become more severe in the Fenwei Plain. Using OMI/Aura OMAERUV L2 and PM 2.5 data, spatial autocorrelation analysis and back trajectory modeling were used to explore the spatio-temporal patterns of absorptive aerosols over the Fenwei Plain, and the dominant types, transmission paths, and potential source areas were identified. The main results can be summarized as follows:① Annual mean absorbing aerosol index (AAI) values increased between 2005 and 2019, with high period occurring in 2006, 2013, and 2017, with values exceeding 0.63. Xi'an and Linfen were identified as a 'high-high' cluster, with AAI showing poor spatial stability and a 15.3% increase in area over the past 15 years. In contrast, the area connecting Xi'an and Linfen, which occupies 24.2% of the total area of the region, was identified as a 'low-low' cluster, with a sharp drop of 6.2% in area; ② The Fenwei Plain has high AAI values across a large area in winter, exceeding 0.8 in Linfen and Xi'an, and 91.5% of the study area exceeding 0.6. Values were lower in spring (AAI>0.4) and autumn (AAI>0.3), with the lowest values occurring in summer. The atmospheric diffusion conditions in spring, autumn, and winter are poor, associated with anticyclonic high-pressure events. The observed high AAI values were significantly affected by atmospheric diffusion conditions, temperature, and precipitation; ③ Back trajectory and source contribution modeling showed that long-range transport of air masses from Xi'an and Linfen occurs from the northwest, and short-range transport air masses occurs from the east and south. Two long-range sand and dust source areas were determined (with northwestern and northern wind sources); two carbon source areas were identified (with eastern and southern wind sources); and one combined sand and carbon source area was identified (from the Loess Plateau). Of these sources, the northwestern wind source, the Loess Plateau, and the southern wind source have significant influence in Xi'an, and the eastern wind source and the Loess Plateau have a significant impact on Linfen. Linfen is little affected by the northwestern wind source and the dust from the northern wind source. Based on the spatial distribution of CO and its correlation with AAI, it is concluded that cardon in the dominant absorbent aerosol in Linfen dust and carbon are most important in Xi'an.

Background: The prevalence of skin diseases and diabetes mellitus (DM) are prominent around the world. The current scope of knowledge regarding the prevalence of skin diseases and comorbidities with type 2 DM (T2DM) is limited, leading to limited recognition of the correlations between skin diseases and T2DM., Methods: We collected 383 subjects from the Da Qing Diabetes Study during the period from July 9th to September 1st, 2016. The subjects were categorized into three groups: Normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. The prevalence and clinical characteristics of skin diseases were recorded and investigated., Results: In this cross-sectional study, 383 individuals with ages ranging from 53 to 89-year-old were recruited. The overall prevalence of skin diseases was 93.5%, and 75.7% of individuals had two or more kinds of skin diseases. Additionally, there were 47 kinds of comorbid skin diseases in patients with T2DM, of which eight kinds of skin diseases had a prevalence >10%. The prevalence of skin diseases in NGT, IGT, and T2DM groups were 93.3%, 91.5%, and 96.6%, respectively; stratified analysis by categories showed a statistically significant difference in "disturbances of pigmentation" and "neurological and psychogenic dermatoses". The duration of T2DM also significantly associated with the prevalence of "disturbances of pigmentation" and "neurological and psychogenic dermatoses". Subsequently, the prevalence of "disturbances of pigmentation" was higher in males than females in NGT (P < 0.01) and T2DM (P < 0.01) groups. In addition, the difference in the prevalence of "disturbances of pigmentation" was also significant in NGT and T2DM groups (P < 0.01)., Conclusions: There was a high prevalence of skin diseases in the Da Qing Diabetes Study. To address the skin diseases in the Da Qing Diabetes Study, increased awareness and intervention measures should be implemented., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Running-related injuries among trail runners are very common and footwear selection may modulate the injury risk. However, most previous studies were conducted in a laboratory environment. The objective of this study was to examine the effects of two contrasting footwear designs, minimalist (MIN) and maximalist shoes (MAX), on the running biomechanics of trail runners during running on a natural trail. Eighteen habitual rearfoot strike trail runners completed level, uphill and downhill running at their preferred speeds in both shod conditions. Peak tibial acceleration, strike index and footstrike pattern were compared between the two footwear and slopes. Interactions of footwear and slope were not detected for all the selected variables. There was no significant effect from footwear ( F  = 1.23, p  = 0.27) and slope ( F  = 2.49, p  = 0.09) on peak tibial acceleration and there was no footwear effect on strike index ( F  = 3.82, p  = 0.056). A significant main effect of slope on strike index ( F  = 13.24, p  < 0.001) was found. Strike index during uphill running was significantly greater (i.e. landing with a more anterior foot strike) when compared with level ( p  < 0.001, Cohen's d  = 1.72) or downhill running ( p  < 0.001, Cohen's d  = 1.44) in either MIN or MAX. The majority of habitual rearfoot strike runners switched to midfoot strike during uphill running while maintaining a rearfoot strike pattern during level or downhill running. In summary, wearing either one of the two contrasting footwear (MIN or MAX) demonstrated no effect on impact loading and footstrike pattern in habitual rearfoot strike trail runners running on a natural trail with different slopes.

Osteoporosis is a health problem to cause global concern. A lot of methods have been used to prevent and treat osteoporosis, but there is still a lack of effective treatment for osteoporosis owing to limited understanding of its mechanism. Therefore, the aim of this present study is to explore the underlying mechanism of Wuling Powder, a traditional Chinese medicine on treating osteoporosis. In this study, we firstly screened and identified the common targets between Wuling Powder and osteoporosis through the related databases, and then explored the relationships among these targets, Wuling Powder and osteoporosis by using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and network analyses. Subsequently, the molecular docking was performed by using systemsDock to evaluate the potential binding relationships between the active components of Wuling Powder and their related targets. The results showed that in total of 14 common targets including CREBBP, ADAM17, GOT1, GAPDH, USP8, ERBB2, EEF1A1, MTOR, RAC1, ETS1, DDX58, GCK, EGF and S100A8 were screened. EGF, ERBB2, MTOR and HIF-1 were the potential therapeutic targets for osteoporosis, and they were also the related targets for predicting active components in Wuling Powder. Taken together, we concluded that Wuling Powder might be used to treat osteoporosis through above these targets., (Copyright © 2021 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Objective: Dermoscopy is a useful technique for improving the diagnostic accuracy of various types of skin disorders. In China, dermoscopy has been widely accepted, and domestic researchers have made tremendous progress in the field of dermoscopy. The main purpose of this review is to summarize the current status of dermoscopy in China and identify its future directions., Data Sources: Articles included in this review were obtained by searching the following databases: Wanfang, China National Knowledge Infrastructure, PubMed, and the Web of Science. We focused on research published before 2019 with keywords including dermoscopy, dermoscopic, dermoscope and trichoscopy., Study Selection: A total of 50 studies were selected. Of these studies, 20 studies were in Chinese and 30 in English, research samples of all the studies were collected from Chinese populations., Results: Since 2000, more than 380 articles about dermoscopy have been published in domestic or foreign journals. Dermoscopy can improve the diagnostic accuracy of neoplastic diseases, evaluating the therapeutic effect of treatment, and determining the treatment endpoint, and it can also assist in the differential diagnosis of inflammatory diseases and in the assessment of the severity of the disease. In addition, researches about the applications of dermoscopy during surgical treatment have been published. Training courses aiming to improve the diagnostic ability of dermatologists, either face-to-face or online, have been offered. The Chinese Skin Image Database, launched in 2017 as a work platform for dermatologists, has promoted the development of dermoscopy in China. Computer-aided diagnostic systems based on the Chinese population are ready for use. In the future, cooperation, resource sharing, talent development, image management, and computer-aided diagnosis will be important directions for the development of dermoscopy in China., Conclusion: Dermoscopy has been widely used and developed in China, however, it still needs to address more challenges in the future.

Health medicine has been the direction of the development of medicine. However, the definition of health defined by Western medicine and traditional medicine cannot completely cover the full meaning of health. Therefore, we propose the new concept of health: health is a state of physical and mental harmony of different individuals in the life process with the environment, and good self-adaptive and regulation ability to natural and social environment. The new concept of health enriches the connotation of health defined by Western medicine and improves the understanding of health in the past, which provide the conceptual basis for further study on health medicine.

Fucoxanthin is a natural carotenoid that had never been previously demonstrated to have anti-tumor effect on human gastric adenocarcinoma SGC-7901 or BGC-823 cells. Here it was found to inhibit proliferation and induce apoptosis through JAK/STAT signal pathway in these cells; the mechanism by which this occurred was investigated. We find that fucoxanthin significantly increased the number of apoptotic cells by propidium iodide (PI) dye staining and flow cytometry. Fucoxanthin (50 or 75 μM) induced SGC-7901 cells cycle arrest at S phase, while BGC-823 cells arrest at G2/M phase. RT-PCR and western blot analysis revealed that the expressions of Mcl-1, STAT3 and p-STAT3 were obviously decreased by fucoxanthin in a dose-dependent manner. Synthetic siRNA targeting Mcl-1 was transfected into cells which had no effect on expressions of STAT3. After pretreatment with AG490 (50 μM) which led to blocking of the JAK/STAT signal pathway, the reductive expressions of Mcl-1, STAT3 and p-STAT3 caused by fucoxanthin were inhibited. This is the first analysis of effects on SGC-7901 and BGC-823 cells by fucoxanthin. Fucoxanthin can induce cell-cycle arrest and apoptosis in these cells. These effects involved downregulation of Mcl-1, STAT3 and p-STAT3. This work is significant for better understanding of mechanisms leading to human gastric adenocarcinoma formation and informing exploitation of anti-tumor marine drug, and for providing Mcl-1 and STAT3 as potential therapeutic targets for gastric adenocarcinoma.

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Objective: This study aimed to gain information on the antimicrobial susceptibility and molecular epidemiological typing of Neisseria gonorrhoeae (NG) isolates in China in 2012., Methods: A total of 244 NG isolates were consecutively recovered from patients with uncomplicated gonorrhea attending sexually transmitted disease clinics in 3 Chinese cities-Guangzhou, Nanjing, and Tianjin-in 2012. Neisseria gonorrhoeae susceptibilities to penicillin and tetracycline were examined by detecting penicillinase-producing NG (PPNG) and high-level tetracycline-resistant NG, and NG susceptibilities to ciprofloxacin, spectinomycin, ceftriaxone, and cefixime were determined using an agar dilution method. Neisseria gonorrhoeae isolates were typed by multiple-locus variable number tandem repeat analysis. We conducted a χ analysis to compare clusters with Bonferroni correction and Kruskal-Wallis test., Results: Neisseria gonorrhoeae isolates gathered from the 3 cities differed significantly in the prevalence of tetracycline-resistant NG (P < 0.001) and NG treated with ceftriaxone with a minimum inhibitory concentration of 0.125 mg/L or higher (P < 0.001). The analysis of the combination of the 7 variable number of tandem repeats loci for all of the 244 isolates yielded 110 multiple-locus variable number tandem repeat analysis types falling into 5 clusters. Cluster III was associated with PPNG, whereas cluster II was associated with non-PPNG (P < 0.05) and NG treated with ceftriaxone with a minimum inhibitory concentration of 0.125 mg/L or higher (P < 0.05)., Conclusions: Antimicrobials that can be used with confidence to treat NG infection currently in China include ceftriaxone and spectinomycin, but not penicillin, tetracycline, ciprofloxacin, and cefixime. Moreover, some of the resulting clusters were associated with PPNG and NG with decreased ceftriaxone susceptibility.

Background: Palmoplantar erythrodysesthesia is a frequent dermal side-effect during chemotherapy. Previous investigations showed radical formation subsequent to doxorubicin infusion and preventative and therapeutic effects of an antioxidant-containing ointment., Patients and Methods: Using a non-invasive vivomeasuring system (Biozoom®; Biozoom Services GmbH, Kassel, Germany) changes in the antioxidant status (as measured by relative carotenoid concentration) of the skin prior to and after intravenous administration of paclitaxel, docetaxel and 5-fluorouracil were investigated in 42 patients with cancer., Results: A significant decrease of antioxidant concentration subsequent to intravenous administration was found for all investigated chemotherapeutic agents. The mean concentration of carotenoids decreased from 3.59±1.26 arbitrary units (a.u.) to 3.41±1.28 a.u. (p<0.001) after paclitaxel administration, from 6.33±2.43 to 5.63±2.29 a.u. after docetaxel (p=0.027) and from 4.26±1.81 to 3.98±1.53 a.u. (p=0.042) after 5-fluorouracil infusion., Conclusion: Oxidative stress might play a significant role in the pathomechanism of palmoplantar erythrodysesthesia associated with paclitaxel, docetaxel and 5-fluorouracil. Therefore, an antioxidant-containing ointment might serve as preventative and therapeutic option., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

As widely used pesticides, organophosphate, pyrethroid, and neonicotinoid insecticides have different modes of action. In the present study, we evaluated individual and joint acute toxicities of two organophosphates, two pyrethroids, and two neonicotinoids against the second-instar silkworm by feeding silkworm with the insecticide-treated mulberry leaves. The 96-h lethal concentration 50 (LC(50)) values of chlorpyrifos, acephate, imidacloprid, thiamethoxam, cypermethrin, and deltamethrin against silkworm were 3.45 (2.95-4.31), 44.45 (39.34-48.56), 1.27 (1.19-1.35), 2.38 (2.19-2.54), 0.36 (0.30-0.43), and 0.037 (0.033-0.041) mg/liter, respectively. Moreover, the 96-h LC(50) values of 50:50 binary mixtures of insecticides against silkworm ranged from 0.048 (0.043-0.054) to 3.52 (2.09-4.51) mg/liter. In addition, the combination coefficient (Q) values of all tested mixtures ranged from 0.36 to 3.37. According to the obtained Q values, the binary mixture of deltamethrin-chlorpyrifos showed antagonistic effects at 96-h interval, while the other binary mixtures had additive effects. Taken together, our results provided valuable guidelines in assessing the ecological risk of these insecticide mixtures against silkworm., (© The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Trichoepithelioma is a benign neoplasm that primarily shows follicular germinative differentiation. Classic trichoepithelioma typically presents as a skin-colored papule or nodule on the face or upper trunk; lesions have a predilection for the nose. Trichoepithelioma can be sporadic or familial and solitary or multiple. Most previously reported multiple trichoepithelioma cases are familial, and germline CYLD mutations could be detected in some patients. We performed mutational analysis of the germline CYLD gene in 8 Chinese multiple trichoepitheliomas patients, 6 of which were sporadic cases. A heterozygous missense mutation (c.1112C>A) in the 9th exon of the CYLD gene was detected in some mother-daughter patients. However, the germline CYLD mutation could not be detected in the 6 non-familial cases. The results suggest that the pathogenesis of sporadic multiple trichoepitheliomas may differ from that of familial cases. Our findings also further confirmed the genetic heterogeneity of multiple trichoepitheliomas.

The cutaneous carotenoid concentration correlates with the overall antioxidant status of a person and can be seen as biomarker for nutrition and lifestyle. 50 high school students were spectroscopically measured for their cutaneous carotenoid concentrations initially in a static phase, followed by an intervention phase with biofeedback of their measured values, living a healthy lifestyle and on healthy food this time. The volunteers showed higher carotenoid concentrations than found in previous studies. A significant correlation of healthy lifestyle habits and a high antioxidant status could be determined. Subjects improved their nutritional habits and significantly increased their carotenoid concentration during intervention. Follow-up five months later showed a consolidation of the increase. The investigations show that a healthy diet and a well-balanced lifestyle correlate with a high cutaneous antioxidant concentration and that spectroscopic biofeedback measurement of cutaneous carotenoids as part of an integrated prevention program is a feasible and effective means to raise the health awareness in adolescents., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Objectives: To monitor the frequency of antibiotic resistance of Neisseria gonorrhoeae (NG) in Nanning, China, between 2000 and 2012., Methods: The production of β-lactamase by NG isolates was determined using the paper acidometric testing method. Antimicrobial susceptibility testing was performed for tetracycline, ciprofloxacin, spectinomycin, and ceftriaxone using the agar dilution method. The χ(2) test, t test, and univariate and multivariate analyses were used to analyze the statistical difference of the results., Results: A total of 923 NG isolates were collected in Nanning between 2000 and 2012. Among these, 131 (14.2%) were penicillinase-producing NG, 520 (56.3%) isolates were tetracycline-resistant NG, and 857 (92.9%) isolates were ciprofloxacin-resistant strains. One spectinomycin-resistant strain was identified in 2000. There were 304 (32.9%) isolates with decreased susceptibility to ceftriaxone; the proportion of such isolates increased from 22.8% in 2000 to 2002 to 48.9% in 2006 to 2008 (P < 0.001), followed by a fall to 32.2% in 2009 to 2012 (P = 0.001). Patients' age of 16 to 25 years and isolate collection period of 2008 to 2012 (except 2011) were demonstrated to be risk factors for infection with isolates with decreased susceptibility to ceftriaxone., Conclusions: Antimicrobial susceptibility of NG isolates obtained from patients in Nanning from 2000 to 2012 was characterized by high occurrence of penicillinase-producing NG, tetracycline-resistant NG, and ciprofloxacin-resistant strains. Spectinomycin and ceftriaxone can be considered drugs of choice for empirical treatment of NG infection in Nanning. Moreover, we recommend a combination of 500 mg or higher dose of intramuscular ceftriaxone and 1 g oral azithromycin be used for the treatment of NG infection in Nanning and possibly in China.

Background: Although Mycoplasma genitalium (MG) is a common sexually transmitted infection (STI), very little information regarding the prevalence of MG among MSM (men who have sex with men) is available in China. The objective of this study was to determine the prevalence of MG among MSM in the city of Shenzhen, Guangdong Province, China, and to identify the potential risk factors associated with MG infection in this population., Methods: Between January and May 2010, a total of 409 MSM were recruited in Shenzhen, Guangdong Province, China. An anonymous questionnaire was used to collect information regarding their sociological and sexual behaviors. In addition, their first-void urine (FVU) samples and rectal swabs were collected for PCR-based MG testing., Results: Among the 406 FVU and 405 rectal swab samples were collected from 409 MSM, the overall MG prevalence was 8.1% (33/406, 95% CI 5.7%-10.6%), with a FVU positivity of 3.4% (95% CI 1.7%-5.4%) and a rectal positivity of 5.4% (95% CI 3.5%-7.7%). Using both univariate and multivariable logistic regression analyses, urethral MG infection was significantly associated with having more heterosexual behaviors (AOR 7.16, 95% CI 1.89-27.13), and with having unprotected anal intercourse in the past six months (AOR 4.80, 95% CI 1.40-16.47). Rectal MG infection was significantly associated with HIV infection based on univariate logistic regression analysis (OR = 4.49, 95% CI 1.18-17.12)., Conclusions: In this study, we investigated the prevalence of MG infection in the population of interest, as determined from both urethral and rectal specimen. We showed that MG was more prevalent in MSM who had bisexual behaviors compared to those who engaged only in homosexual behaviors. Further work is needed to establish the mode of MG transmission and to identify its role in HIV transmission. Meanwhile, more attention should be paid to MG infection among MSMs, and especially bisexual MSMs, which might have critical implications for effective HIV/STD control in China.

Background: Neisseria gonorrhoeae (NG) infection is a serious public health problem. The third-generation extended-spectrum cephalosporins (ESCs) have been used as the first-line treatment for NG infection for almost three decades. However, in recent years, treatment failures with the oral third-generation ESCs have been reported worldwide. This study aimed to estimate worldwide susceptibility rates of NG to cefixime and cefpodoxime by analyzing data from all relevant published studies., Methodology/principal Findings: Two researchers independently searched five databases to identify studies on susceptibilities of NG to cefixime and cefpodoxime published between January 1, 1984 and October 15, 2012. A fixed-effect model was used to perform group analysis, and a χ2 test was employed to make subgroup comparison. Publication bias was assessed with the Begg rank correlation test. The pooled susceptibility rate of NG isolates to cefixime was 99.8% (95% CI: 99.7%-99.8%). The cefixime susceptibility rate of NG isolates from men was significantly lower than that from patients without information of gender or from men and women; the susceptibility rate of NG isolates from Asia was significantly lower than that from other continents; and the susceptibility rate of NG isolates collected before or during 2003 was significantly higher than that after 2003. The pooled susceptibility rate of NG isolates to cefpodoxime was 92.8% (95% CI: 89.0%-95.3%), which was lower than that to cefixime (92.8% vs. 99.8%, χ2 = 951.809, P<0.01)., Conclusions: The susceptibility rate of NG isolates to cefixime varied with the gender of patients and geographical location from which NG isolates were collected, and declined with time. The reported lower susceptibility rate of NG isolates to cefixime and associated treatment failures, as well as the emergence of NG strains with cephalosporin resistance call for the more effective control of NG infection and the development of new antibiotics.

The objective of this study was to determine the prevalence of urethral Mycoplasma genitalium infections among male patients attending a sexually transmitted disease (STD) clinic in China and identify risk factors associated with this disease. A total of 423 patients were recruited in Hezhou City, Guangxi Province, China, and each was requested to complete a questionnaire regarding sociological and sexual behaviors. First-void urine samples were collected for M. genitalium analysis by polymerase chain reaction. Of the 406 urine samples collected, 114 were M. genitalium-positive, giving a prevalence rate of 28.1%. Univariate logistic regression analysis showed that M. genitalium infection was associated with younger age, having received at least senior high school education, and single marital status. In both univariate and multivariate logistic regression analyses, M. genitalium infection was found to be associated with lack of symptoms for STD in the past year (adjusted odds ratio [AOR] = 2.839; 95% CI = 1.495-5.392; P = 0.001), no use of condoms with steady partners in the past year (AOR = 2.830; 95% CI = 1.468-5.455; P = 0.002), and having sexual encounters with female sexual workers within the past 3 months (AOR = 2.955; 95% CI = 1.637-5.336; P < 0.0003). The observed high rate of M. genitalium infection among male STD patients in Hezhou City indicates an M. genitalium epidemic in the study population; thus, the national surveillance program and clinical health providers in China should more closely monitor this disease.

Background: The antioxidant status of the human skin provides protection against the destructive action of free radicals. Most antioxidants cannot be synthesized by the human organism itself, but have to be ingested with a healthy nutrition rich in fruit and vegetables. The Korean cuisine is known to be one of the healthiest worldwide. This binational study investigated the cutaneous carotenoid concentrations in German subjects, South Korean subjects and immigrant Korean subjects resident in Germany and examined whether dietary- and lifestyle-related differences are reflected in the cutaneous carotenoid concentrations., Methods: Measurements of the carotenoid concentrations of 714 healthy volunteers were performed using a non-invasive spectroscopic measurement system based on reflectance spectroscopy., Results: In the present study South Korean residents showed a significantly higher antioxidant status than both native German residents and Korean immigrants living in Germany (p < 0.001). The first generation of Korean immigrants to Germany over the age of 50 mostly preserved Korean dietary habits, showing significantly higher concentrations (p < 0.001) than the German-born second and third Korean generations under the age of 50., Conclusion: The results of the study indicate that a healthy nutrition alone does not provide a high antioxidant status unless the stress exposure can be reduced simultaneously., (© 2014 S. Karger AG, Basel.)

Background: This study aimed to investigate the prevalence of penicillinase-producing Neisseria gonorrhoeae (PPNG) and their blaTEM-135 gene variant in 2007 and 2012 in Nanjing, China. In addition, molecular epidemiological typing of all isolates was performed to elucidate the genetic relationships of the PPNG strains., Methods: A total of 199 and 77 N. gonorrhoeae isolates were collected at the National Center for STD Control in 2007 and 2012, respectively. Nitrocefin tests were performed to identify PPNG. Mismatch amplification mutation assay was used to identify blaTEM-135. All isolates were genotyped using N. gonorrhoeae multiantigen sequence typing (NG-MAST), and additionally, porB-based phylogenetic analysis was performed for the PPNG isolates., Results: The total prevalence of PPNG isolates was 41% (114/276) and 58% (66/114) of these PPNG isolates possessed bla(TEM-135). In 2007, 45% (90/199) produced β-lactamase, and of those PPNG, 58% (52/90) possessed bla(TEM-135). In 2012, 31% (24/77) were PPNG, and 58% (14/24) of those isolates contained bla(TEM-135). There were 162 NG-MAST STs among the 276 isolates, and 89 of those were novel STs. A strong association between specific NG-MAST STs and bla(TEM-135) was found, and the porB-based phylogenetic analysis showed a distant evolutionary relationship between isolates in 2007 and isolates in 2012., Conclusions: A high prevalence of PPNG and blaTEM-135 was found in Nanjing, China. bla(TEM-135) might be a precursor in the evolution into an extended-spectrum β-lactamase that can degrade ceftriaxone, which stresses the need to continuously monitor PPNG, blaTEM-135, and additional evolving blaTEM gene variants.

In this study, we investigated the anti-tumor effects and possible mechanisms of fucoxanthin, which has been reported to inhibit tumor proliferation and induce apoptosis in vitro or in vivo. Human gastric adenocarcinoma MGC-803 cells were treated with fucoxanthin (25μM, 50μM or 75μM). Data of flow cytometry revealed that fucoxanthin (50μM or 75μM) increased the ratio of cell in G2/M phase and apoptotic MGC-803 cells varying on a dose-dependent manner. Results from reverse transcriptase-polymerase chain reaction and Western blot showed that treatment with fucoxanthin (50μM or 75μM) significantly decreased the expressions of CyclinB1, survivin and STAT3 in MGC-803 cells in a dose-dependent manner both at the time of 24h and 48h. In addition, immunofluorescence microscopy analysis also revealed the suppressed expressions of CyclinB1 and survivin by fucoxanthin. After pretreatment with AG490 (the inhibitor for JAK/STAT signal pathway), the expressions of p-STAT3 and survivin remained also slightly lower than the vehicle control group. Co-treated with fucoxanthin (75μM) and AG490, the reduction on the expressions of STAT3, p-STAT3 and CyclinB1 by fucoxanthin were attenuated while that of survivin was enhanced. Taken together, fucoxanthin can down-regulate the expressions of CyclinB1 and survivin, inducing cell cycle arrest in G2/M phase, and apoptosis in MGC-803 cells. The reduction of CyclinB1 by fucoxanthin was associated with JAK/STAT signal pathway., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The low rate of approval of novel anti-cancer agents underscores the need for better preclinical models of therapeutic response as neither xenografts nor early-generation genetically engineered mouse models (GEMMs) reliably predict human clinical outcomes. Whereas recent, sporadic GEMMs emulate many aspects of their human disease counterpart more closely, their ability to predict clinical therapeutic responses has never been tested systematically. We evaluated the utility of two state-of-the-art, mutant Kras-driven GEMMs--one of non-small-cell lung carcinoma and another of pancreatic adenocarcinoma--by assessing responses to existing standard-of-care chemotherapeutics, and subsequently in combination with EGFR and VEGF inhibitors. Standard clinical endpoints were modeled to evaluate efficacy, including overall survival and progression-free survival using noninvasive imaging modalities. Comparisons with corresponding clinical trials indicate that these GEMMs model human responses well, and lay the foundation for the use of validated GEMMs in predicting outcome and interrogating mechanisms of therapeutic response and resistance.

A major challenge in the post-genome era is to reconstruct regulatory networks from the biological knowledge accumulated up to date. The development of tools for identifying direct target genes of transcription factors (TFs) is critical to this endeavor. Given a set of microarray experiments, a probabilistic model called TRANSMODIS has been developed which can infer the direct targets of a TF by integrating sequence motif, gene expression and ChIP-chip data. The performance of TRANSMODIS was first validated on a set of transcription factor perturbation experiments (TFPEs) involving Pho4p, a well studied TF in Saccharomyces cerevisiae. TRANSMODIS removed elements of arbitrariness in manual target gene selection process and produced results that concur with one's intuition. TRANSMODIS was further validated on a genome-wide scale by comparing it with two other methods in Saccharomyces cerevisiae. The usefulness of TRANSMODIS was then demonstrated by applying it to the identification of direct targets of DAF-16, a critical TF regulating ageing in Caenorhabditis elegans. We found that 189 genes were tightly regulated by DAF-16. In addition, DAF-16 has differential preference for motifs when acting as an activator or repressor, which awaits experimental verification. TRANSMODIS is computationally efficient and robust, making it a useful probabilistic framework for finding immediate targets.

Aim: To evaluate the preventive effects of phosphorus-32 glass microspheres (P32-GMS) in the recurrence of massive hepatocellular carcinomas (HCCs) after tumor resection., Methods: Twenty-nine patients with massive HCCs received local P32-GMS implantation after liver tumors were removed, while the other 38 patients with massive HCCs were not treated with P32-GMS after hepatectomies. The radioactivity of the blood, urine and liver were examined. The complications, HCC recurrence and overall survival rates in the patients were analyzed., Results: P32-GMS implanted in the liver did not cause systemic absorption of P32. There were no significant differences of postoperative complications between the patients with and without P32-GMS treatment. The short-term (six months and 1 year) and long-term (2, 3 and over 3 years) recurrence rates in patients who received P32-GMS radiotherapy were significantly decreased, and the overall survival rates in this group were significantly improved., Conclusion: P32-GMS implantation in the liver can significantly decrease the postoperative recurrence and improve the overall survival in HCCs patients after hepatectomy. This therapy may provide an innovative method in prevention of HCC recurrence after operation.

The objective of study was to investigate whether U937 cells-loaded dendritic cells (DCs) could induce anti-leukemic immune activity. The apoptosis of U937 cells was induced by artesunate (ART). DCs derived from peripheral blood mononuclear cells of health donors were loaded with apoptotic U937 cells, and induced to maturation in the presence of TNF-alpha. Matured DCs were cocultured with autologous T-lymphocytes, and combined with IL-2 in order to induce the leukemia-specific CTL. The phenotypes of DCs and T lymphocytes were tested by flow cytometry. The ability of DC capturing antigens was measured by Dextran-FITC endocytosis. The IL-12p70 level was assayed by ELISA kit. The proliferation of CTL and CTL activity were measured by MTT assay. The results showed that the apoptotic rate of the U937 cells was 51.2% when U937 cells were induced by 1 microg/ml ART for 48 hours in vitro. DCs had the most powerful ability of endocytosis in its immature phase. Apoptotic U937 cells could not induce the features of DC maturation, and apoptotic U937 cell-pulsed immature DCs could be matured with TNF-alpha. The IL-12p70 level secreded by apoptotic U937 cell-loaded mature DCs (mDC-(Apo)U937) was higher than that of non-loaded mDC. The proliferation of autologous T lymphocytes co-cultured with mDC-(Apo)U937 was significantly remarkable and the content of CD8(+) CTL was significantly higher in comparison with any other groups. CTL induced by mDC-(Apo)U937 had stronger killing effect on U937 cells than NB4 (p < 0.01). It is concluded that the mDC-(Apo)U937 can effectively generate T cell-mediated dendritic antileukemic responses in vitro.

The morphology and ultrastructure of testes and accessory glands along with the characterization of their secretions were investigated for a braconid species Cotesia vestalis (Hymenoptera: Braconidae) using light and electron microscopes. The male internal reproductive system of this species is distinguished by a pair of testes, one vas deferens, and a pair of male accessory glands. The testes are separate, and the accessory glands are oval and not fused. It was observed that the secretory cells of testes have characteristic smooth and rough endoplasmic reticulum, and that the cytoplasm is filled with an array of granule droplets usually of two to three types. The secretory cells in the case of accessory glands are typified by the presence of microvilli on their apical cell surfaces and numerous mitochondria in their cytoplasm. SDS-PAGE profile when performed depicted a similarity in most bands of the secretions from both testes and accessory glands, except for four proteins of which two were present only in testes, while the other two only appeared in accessory glands. Their molecular weights were 117 and 55 kDa for testes and 196 and 30 kDa for accessory glands, respectively. This study gives new insights into the intriguing features of male internal reproductive system and it especially constitutes the first report of its kind about the secretion properties of these organs in C. vestalis.

The study was aimed to investigate the effect of artesunate (ART) on the apoptosis of HL-60 cells in vitro and the expression of Bcl-2 and ICAD in the process of apoptosis induced by ART. The inhibition of ART on HL-60 cells were evaluated by means of MTT assay; cell apoptosis was detected by light microscopy, agarose gel electro-phoresis, flow cytometry; Western blot was used to analyze the expression of Bcl-2 and ICAD in cells during apoptosis induced by ART. The results showed that ART could significantly inhibit the proliferation of HL-60 cells in time-and dose-dependent manner. After treating HL-60 cells with ART for 48 hours, the IC(50) values was 18.33 microg/ml and its inhibition effect contributed to the induced apoptosis. Bcl-2 and ICAD proteins both all expressed in HL-60 cells, the level of expression declined as concentration increased. It is concluded that artesunate may induce apoptosis of HL-60 cells in vitro, Bcl-2 and ICAD may be an important control factor in the signal transduction pathway of ART-induced apoptosis.

The endpoints of confirmed response and progression are widely used in oncology clinical trials. These endpoints originated at a time when agents used to treat cancer were primarily cytotoxic. Increasingly agents that are cytostatic are being investigated in combination with agents that are cytotoxic. Since tumor growth rates often depend on the volume of the tumor, combining cytotoxic agents that reduce tumor volume with cytostatic agents may mask the activity of the cytostatic agent. This paper explores the sensitivity of time to progression/progression free survival (TTP/PFS) as an endpoint for evaluating the efficacy of cytostatic drugs when combined with cytotoxic agents. Mathematical models of tumor growth are used to describe tumor growth over time. The models account for the impact of chemotherapy and an agent that slows tumor growth in the context of the Gompertzian growth kinetics. We use a clinical trial of an angiogenesis inhibitor in metastatic breast cancer as a motivating example. We demonstrate that the endpoint TTP/PFS may not be sensitive to the effects of active cytostatic agents when they are combined with chemotherapy, and measuring time to regrowth would be more sensitive to the activity of a cytostatic agent. We conclude that an active cytostatic agent may not appear effective when combined with chemotherapy and evaluated with TTP/PFS in a clinical trial.

Crude venom and calyx fluid from Cotesia plutellae (Hymenoptera Braconidae) were assayed for biological activity toward hemocytes of Plutella xylostella (Lepidoptera Plutellidae). Venom from C. plutellae displayed high activity toward the spreading of plasmatocytes of P. xylostella early in the incubation period, and the inhibition was more severe as the concentration of venom increased. However, most inhibited hemocytes spread normally after being incubated for 4h. No effects were found toward granular cells from the host. Additionally, the venom from C. plutellae had some lethal effects on hemocytes of P. xylostella at high concentrations. In contrast, when incubated with different concentrations of calyx fluid, the spreading of some hemocytes was inhibited, some began to disintegrate, and some were badly damaged with only the nucleus left. After 4h, the majority of hemocytes died. The same results were observed when hemocytes were incubated in calyx fluid together with venom. These results show that calyx fluid from C. plutellae may play a major role in the suppression of the host immune system, whereas venom from C. plutellae has a limited effect on hemocytes and probably synergizes the effect of calyx fluid or polydnavirus.

Objective: To explore the feasibility of human leucocyte antigen (HLA) haploidentical related T-cell undepleted allogeneic bone marrow transplantation (Allo-BMT) combined with Chinese medicine for the treatment of leukaemia., Methods: Four patients with chronic myeloblastic leukemia (CML) and 4 with acute myeloid leukemia (AML) received allo-BMT with graft from 1 - 3 HLA-mismatched related donors. All patients were pre-treated with standardized conditioning regimen consisting of high dose Ara-c, cyclophosphamide (CY) and total body irradiation (TBI) or busulfan. Donors were given G-CSF 250 microg/d for 7 days prior to marrow harvest. To prevent GVHD, besides application of CSA and MTX, ATG 2.5 mg/kg was given everyday for 4 days before transplantation, and MMF 1.0 g per day starting from the 7th day after transplantation. Chinese medicine for replenishing qi and yin and strengthening Pi and Wei was administrated orally after transplantation., Results: Successful haematopoietic reconstruction was seen in all patients. The median days for reaching of granulocyte >0.5 X 10(9)/L and platelet > 20 x 10(9)/L were 12 (range 10-14) and 20 (range 18-25) days respectively. GVHD of skin in various grade was seen in 7 patients, among whom only one advanced to grade IV; besides, 2 accompanied with GVHD of gut, one with hemorrhagic cystitis, one died for concurrent infection on the 81st day, and one left hospital of his own accord on the 46th day. The median follow-up duration was 18 (range 2-32) months, during this period six patients were alive in a disease-free situation., Conclusion: Combined therapy of HLA haploidentical related T-cell undepleted Allo-BMT and Chinese medicine plus immunosuppressants with pre-harvest G-CSF application in doner could effectively reduce the incidence of acute severe GVHD and raise the disease-free survival rate in treating leukaemia.

Taxanes are important drugs in the treatment of ovarian and other cancers, but their efficacy is limited by intrinsic and acquired drug resistance. Expression of the multidrug transporter P-glycoprotein, encoded by the MDR1 (ABCB1) gene, is one of the causes of clinical drug resistance to taxanes. To study the mechanisms of MDR1 activation related to taxanes, we established 11 multidrug-resistant variants from six ovarian cancer cell lines by continuous exposure to either paclitaxel or docetaxel. We profiled gene expression and gene copy number alterations in these cell lines using cDNA microarrays and identified a cluster of genes coactivated with MDR1 in 7q21.11-13. Regional activation was evident in nine resistant variants displaying a coexpression pattern of up to 22 genes over an 8-Mb area, including SRI, MGC4175, CLDN12, CROT, and CDK6. In six of these variants, regional activation was driven by gene copy number alterations, with low-level gains or high-level amplifications spanning the involved region. However, three variants displayed regional increases in gene expression even without concomitant gene copy number changes. These results suggest that regional gene activation may be a fundamental mechanism for acquired drug resistance, with or without changes in gene dosage. In addition to numerical and structural chromosomal changes driven by genome instability in cancer cells, other mechanisms might be involved in MDR1 regional activation, such as chromatin remodeling and DNA or histone modifications of the 7q21 region.

Purpose: Pre-existing and acquired drug resistance are major obstacles to the successful treatment of glioblastomas., Methods: We used an integrated resistance model and genomics tools to globally explore molecular factors and cellular pathways mediating resistance to O6-alkylating agents in glioblastoma cells., Results: We identified a transcriptomic signature that predicts a common in vitro and in vivo resistance phenotype to these agents, a proportion of which is imprinted recurrently by gene dosage changes in the resistant glioblastoma genome. This signature was highly enriched for genes with functions in cell death, compromise, and survival. Modularity was a predominant organizational principle of the signature, with functions being carried out by groups of interacting molecules in overlapping networks. A highly significant network was built around nuclear factor-kappaB (NF-kappaB), which included the persistent alterations of various NF-kappaB pathway elements. Tumor necrosis factor-alpha-induced protein 3 (TNFAIP3) was identified as a new regulatory component of a putative cytoplasmic signaling cascade that mediates NF-kappaB activation in response to DNA damage caused by O6-alkylating agents. Expression of the corresponding zinc finger protein A20 closely mirrored the expression of the TNFAIP3 transcript, and was inversely related to NF-kappaB activation status in the resistant cells. A prediction model based on the resistance signature enabled the subclassification of an independent, validation cohort of 31 glioblastomas into two outcome groups (P = .037) and revealed TNFAIP3 as part of an optimized four-gene predictor associated significantly with patient survival (P = .022)., Conclusion: Our results offer strong evidence for TNFAIP3 as a key regulator of the cytoplasmic signaling to activate NF-kappaB en route to O6-alkylating agent resistance in glioblastoma cells. This pathway may be an attractive target for therapeutic modulation of glioblastomas.

Aim: To improve the low resection rate, poor prognosis and to control the massive hemorrhage during operation, total vascular exclusion (TVE) technique was used in hepatectomies of advanced and complicated hepatocellular carcinomas (HCCs)., Methods: Five hundred and thirty patients with HCCs were admitted in our hospital. They were divided into TVE technique group (group A: n=78), Pringle maneuver method group (group B: n=176) and unresectable group (group C: n=276). The clinical, operative, pathological parameters and outcome of the patients were statistically evaluated., Results: Group A had a significantly higher resection rate than group B (accounting for 47.92% and 33.21% respectively). There was no significant difference in blood loss, blood transfusion and perioperative mortality between groups A and B. Both groups had the similar median disease free survival time (14.6 vs 16.3 months) and 1 year survival rate (92.9% vs 95.5%). The TVE group had a medial survival time of 40.5 months and its 5-year survival rate was 34.6%., Conclusion: As compared with Pringle maneuver method, the total vascular exclusion is a safe and effective technique to increase the total resection rate of advanced and complicated HCCs.