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Natural killer cells from acute myeloid leukaemia patients (AML-NK) show a dramatic impairment in cytotoxic activity. The exact reasons for this dysfunction are not fully understood. Here we show that the glycogen synthase kinase beta (GSK3β) expression is elevated in AML-NK cells. Interestingly, GSK3 overexpression in normal NK cells impairs their ability to kill AML cells, while genetic or pharmacological GSK3 inactivation enhances their cytotoxic activity. Mechanistic studies reveal that the increased cytotoxic activity correlates with an increase in AML-NK cell conjugates. GSK3 inhibition promotes the conjugate formation by upregulating LFA expression on NK cells and by inducing ICAM-1 expression on AML cells. The latter is mediated by increased NF-κB activation in response to TNF-α production by NK cells. Finally, GSK3-inhibited NK cells show significant efficacy in human AML mouse models. Overall, our work provides mechanistic insights into the AML-NK dysfunction and a potential NK cell therapy strategy. Natural killer cells of acute myeloid leukaemia patients lack cytotoxic activity. Here the authors show that these cells have elevated GSK3β, and that its inhibition prolongs survival of mice transplanted with human AML and stimulates NK cytotoxicity via increased adhesion of NK cells to their targets.

Despite the fact that AML is the most common acute leukemia in adults, patient outcomes are poor necessitating the development of novel therapies. We identified that inhibition of Thioredoxin Reductase (TrxR) is a promising strategy for AML and report a highly potent and specific inhibitor of TrxR, S-250. Both pharmacologic and genetic inhibition of TrxR impairs the growth of human AML in mouse models. We found that TrxR inhibition leads to a rapid and marked impairment of metabolism in leukemic cells subsequently leading to cell death. TrxR was found to be a major and direct regulator of metabolism in AML cells through impacts on both glycolysis and the TCA cycle. Studies revealed that TrxR directly regulates GAPDH leading to a disruption of glycolysis and an increase in flux through the pentose phosphate pathway (PPP). The combined inhibition of TrxR and the PPP led to enhanced leukemia growth inhibition. Overall, TrxR abrogation, particularly with S-250, was identified as a promising strategy to disrupt AML metabolism.

Cerebral ischemia-reperfusion injury (IRI), occurring after blood supply restoration, contributes significantly to stroke-related deaths. This study explored the combined impact and mechanisms of astragaloside IV (AS-IV), hydroxysafflor yellow A (HSYA), and their combination in mitigating IRI. Male Sprague–Dawley (SD) rats were randomized to the Sham, MCAO, MCAO+AS-IV, MCAO+HSYA, and MCAO+AS-IV+HSYA groups. Neurological deficits and cerebral infarction were examined after restoring the blood supply to the brain. Pathomorphological changes in the cerebral cortex were observed via HE staining. IL-1β and IL-18 were quantified using ELISA. The expression of NF-κB and GSDMD in the ischemic cerebrum was analyzed using immunohistochemistry. The expression levels of NLRP3, ASC, IL-1β, Caspase-1, and GSDMD in the ischemic cerebrum were evaluated using Western blot. The MCAO+AS-IV, MCAO+HSYA, and MCAO+AS-IV+HSYA groups exhibited notably better neurological function and cerebral infarction compared with the MCAO group. The combined treatment demonstrated superior brain tissue injury alleviation. Reductions in NF-κB, GSDMD positive cells, and NLRP3/ASC/IL-1β/Caspase-1/GSDMD protein expression in the ischemic brain were significantly more pronounced with the combined therapy, indicating a synergistic effect in countering cerebral IRI via the NF-κB/NLRP3/Caspase-1/GSDMD pathway inhibition of cell pyroptosis-induced injury.

The incidence of tuberculosis (TB) and its risk factors in China remains unclear. This study examined TB incidence and relative risk factors in rural areas of China. Participants (n = 177,529) were recruited in Xiangtan County (in the central area of China) and in Danyang County (in the eastern area of China) in 2009 and a followed-up study was conducted for one year. The incidence density of pulmonary TB and smear-positive TB were 91.6 (95% CI: 78.7, 106.0) per 100,000 person-year and 36.7 (95% CI: 33.1, 52.4) per 100,000 person-year respectively in Xiangtan, and 47.3 (95% CI: 38.2, 57.5) per 100,000 person-year and 22.7 (95% CI: 16.5, 30.8) per 100,000 person-year in Danyang. The medical history of TB was associated with TB, with the relative risk (RR) of 7.00 (95% CI: 2.76, 17.18) in Xiangtan and that of 31.08 (95% CI: 13.22, 73.10) in Danyang. The association between TB and per capita living space over median was found in Xiangtan, with the RR of 1.86 (95% CI: 1.15, 3.01). No association was found between TB and the insurance status, the contact history with TB, the history of diabetes, smoking, or per capita annual income. The host genetic susceptibility, and social factors such as education and income could be considered in future studies.

A prediction model for tuberculosis incidence is needed in China which may be used as a decision-supportive tool for planning health interventions and allocating health resources. The autoregressive integrated moving average (ARIMA) model was first constructed with the data of tuberculosis report rate in Hubei Province from Jan 2004 to Dec 2011.The data from Jan 2012 to Jun 2012 were used to validate the model. Then the generalized regression neural network (GRNN)-ARIMA combination model was established based on the constructed ARIMA model. Finally, the fitting and prediction accuracy of the two models was evaluated. A total of 465,960 cases were reported between Jan 2004 and Dec 2011 in Hubei Province. The report rate of tuberculosis was highest in 2005 (119.932 per 100,000 population) and lowest in 2010 (84.724 per 100,000 population). The time series of tuberculosis report rate show a gradual secular decline and a striking seasonal variation. The ARIMA (2, 1, 0) × (0, 1, 1)12 model was selected from several plausible ARIMA models. The residual mean square error of the GRNN-ARIMA model and ARIMA model were 0.4467 and 0.6521 in training part, and 0.0958 and 0.1133 in validation part, respectively. The mean absolute error and mean absolute percentage error of the hybrid model were also less than the ARIMA model. The gradual decline in tuberculosis report rate may be attributed to the effect of intensive measures on tuberculosis. The striking seasonal variation may have resulted from several factors. We suppose that a delay in the surveillance system may also have contributed to the variation. According to the fitting and prediction accuracy, the hybrid model outperforms the traditional ARIMA model, which may facilitate the allocation of health resources in China.

The purpose of this article was to examine the validity and reliability of the LifeWindows Information-Motivation-Behavioral Skills Antiretroviral Therapy (ART) Adherence Questionnaire (LW-IMB-AAQ) among HIV+ patients in Shanghai. We surveyed 426 HIV+ patients in Shanghai's Putuo District to examine the validity and reliability of the questionnaire. The questionnaire includes self-reported demographic characteristics, the modified version of the Community Programs for Clinical Research on AIDS Antiretroviral Medication Self-Report (CPCRA) and LW-IMB-AAQ. CPCRA was used to calculate ART adherence. LW-IMB-AAQ, including the information section, the motivation section and the behavioral skills section, was used to analyze patients' ART adherence. We analyzed data by means, standard deviation, critical ratio, and item-total correlation. Reliability was assessed by internal consistency, split-half reliability, and test-retest reliability. Validity was assessed by exploratory factor analysis (EFA), confirmatory factor analysis (CFA), convergent validity and discriminant validity. Item analysis showed that except for motivation item 1, all items were acceptable. For reliability, Cronbach's alpha coefficients for the three sections and the total scale were all higher than 0.7, with interclass correlation coefficients (ICC) all higher than 0.6 (p<0.001). The Spearman-Brown coefficient for the total scale was 0.825. For validity, results showed that the information section could be divided into two subscales, motivation section and behavioral skills section could be divided into three and two subscales, respectively. The final model demonstrated good validity (p=0.471, /df=0.960, CFI=1.000, GFI=0.994 and RMSEA<0.001) without motivation item 4. Excluding motivation items 1 and 4, the LifeWindows Information-Motivation-Behavioral Skills ART Adherence Questionnaire (LW-IMB-AAQ) demonstrated good validity and reliability among HIV+ patients in Shanghai.

Cet article tente de concevoir un circuit modulable pour amplificateur proportionnel électrohydraulique.Tout d’abord, le principe de contrôle de la modulation de largeur d’impulsion (MLI) de l’amplificateur a été discuté, ainsi que le développement récent de l’amplificateur et les exigences de contrôle de la valve directionnelle proportionnelle. Ensuite, un modèle mathématique a été établi pour le courant bobine de solénoïde proportionnelle. Sur cette base, l'auteur a analysé la méthode de commande de l'amplificateur proportionnel électrohydraulique et a détaillé la conception du circuit de l'amplificateur. La conception proposée a ensuite été vérifiée par un test de contrôle et une simulation logicielle. Les résultats du test concordent bien avec les données de simulation et montre que la conception du circuit est faisable et valide. TITRE Conception de circuit pour amplificateur proportionnel électrohydraulique TITLE Circuit design for electrohydraulic proportional amplifier RÉSUMÉ Cet article tente de concevoir un circuit modulable pour amplificateur proportionnel électrohydraulique.Tout d’abord, le principe de contrôle de la modulation de largeur d’impulsion (MLI) de l’amplificateur a été discuté, ainsi que le développement récent de l’amplificateur et les exigences de contrôle de la valve directionnelle proportionnelle. Ensuite, un modèle mathématique a été établi pour le courant bobine de solénoïde proportionnelle. Sur cette base, l'auteur a analysé la méthode de commande de l'amplificateur proportionnel électrohydraulique et a détaillé la conception du circuit de l'amplificateur. La conception proposée a ensuite été vérifiée par un test de contrôle et une simulation logicielle. Les résultats du test concordent bien avec les données de simulation et montre que la conception du circuit est faisable et valide. ABSTRACT This paper attempts to design a stuiable circuit for electrohydraulic proportional amplifer. Firstly, the pulse width modulation (PWM) control principle of the amplifier was discussed, along with the recent development of the amplifier and the control requirements of proportional direction valve. Then, a mathematical model was established for the proportional solenoid coil current. On this basis, the author analyzed the control method of electrohydraulic proportional amplifier, and detailed the circuit design for the amplifier. The proposed design was then verified through a control test and software simulation. The test results agree well with the simulation data, indicating that the circuit design is feasible and valid. AUTHOR(S) Yongchun HOU MOTS-CLÉS modulation de largeur d'impulsion (MLI), bobine de solénoïdale proportionnelle, amplificateur proportionnel, simulation. KEYWORDS pulse width modulation (PWM), proportional solenoid coil, proportional amplifier, simulation. ARTICLE LANGUAGE English

Cet article tente de détecter des signaux extrêmement faibles et de supprimer les interférences dans la diagraphie de résistivité à travers le casing. Plus précisément, un circuit de conditionnement a été conçu selon des caractéristiques des signaux à mesurer et les principes / méthodes de réalisation ont été spécifiés pour le circuit d'alimentation, le circuit préamplificateur, le circuit amplificateur d'étage intermédiaire et le circuit de filtrage. Le circuit conçu a été vérifié par une expérience. Les résultats montrent que le circuit de conditionnement proposé peut extraire les signaux utiles précisément et supprimer les signaux d'interférence. Les résultats de la recherche donne les nouvelles pistes pour la détection de signaux extrêmement faibles dans la diagraphie de la strate. TITRE Conception d'un circuit de conditionnement de signaux extrêmement faibles pour la diagraphie de la résistivité dans le casing TITLE Design of conditioning circuit for weak signal in through-casing resistivity logging RÉSUMÉ Cet article tente de détecter des signaux extrêmement faibles et de supprimer les interférences dans la diagraphie de résistivité à travers le casing. Plus précisément, un circuit de conditionnement a été conçu selon des caractéristiques des signaux à mesurer et les principes / méthodes de réalisation ont été spécifiés pour le circuit d'alimentation, le circuit préamplificateur, le circuit amplificateur d'étage intermédiaire et le circuit de filtrage. Le circuit conçu a été vérifié par une expérience. Les résultats montrent que le circuit de conditionnement proposé peut extraire les signaux utiles précisément et supprimer les signaux d'interférence. Les résultats de la recherche donne les nouvelles pistes pour la détection de signaux extrêmement faibles dans la diagraphie de la strate. ABSTRACT The detection of extremely weak signals and suppression of interference are the key problems to be solved in through-casing formation resistivity logging. According to the characteristics of the signal to be measured, the signal conditioning circuit is designed. The principle and method for realization of power supply circuit, preamplifier circuit, middlestage amplifier circuit and filter circuit are put forward. The result of measurement shows that conditioning circuit can accurately extract useful signals and suppress interference signals, and achieve the expected design goal. AUTHOR(S) Yongchun HOU MOTS-CLÉS signaux extrêmement faibles, diagraphie de résistivité dans le casing, circuit de conditionnement, circuit d’amplificateur, circuit de filtration. KEYWORDS extremely weak signals, through-casing resistivity logging, signal conditioning circuit, amplifier circuit, filter circuit. ARTICLE LANGUAGE English

Few studies have examined, in a prospective cohort study, factors causing delay of access to tuberculosis (TB) diagnosis among new, active TB patients. A prospective cohort study (2009-2011) was carried out among 408 889 Chinese. Data on known/potential influencing factors were obtained from baseline questionnaires. We used stepwise logistic regression models to analyze the association between several known/potential influencing factors and diagnosis delay, assessed the current situation, and explored determinants of diagnosis delay. During follow-up and final visits, 202 new, active TB patients were found. Median patient delay was 5.4 (quartile 2.7-26) weeks, health system delay was 0 (quartile 0-1.6) weeks, and diagnosis delay was 9.9 (quartile 3.1-28.1) weeks. The influencing factors on patient delay were age and duration of symptoms. Smoking and sputum smear status were influencing factors for health system delay, and duration of symptoms was one of the factors for diagnosis delay. These findings provide information on the current situation of diagnosis delay and evidence for specific strategy development for TB control in China.

Background A prediction model for tuberculosis incidence is needed in China which may be used as a decision-supportive tool for planning health interventions and allocating health resources. Methods The autoregressive integrated moving average (ARIMA) model was first constructed with the data of tuberculosis report rate in Hubei Province from Jan 2004 to Dec 2011.The data from Jan 2012 to Jun 2012 were used to validate the model. Then the generalized regression neural network (GRNN)-ARIMA combination model was established based on the constructed ARIMA model. Finally, the fitting and prediction accuracy of the two models was evaluated. Results A total of 465,960 cases were reported between Jan 2004 and Dec 2011 in Hubei Province. The report rate of tuberculosis was highest in 2005 (119.932 per 100,000 population) and lowest in 2010 (84.724 per 100,000 population). The time series of tuberculosis report rate show a gradual secular decline and a striking seasonal variation. The ARIMA (2, 1, 0) (0, 1, 1)12 model was selected from several plausible ARIMA models. The residual mean square error of the GRNN-ARIMA model and ARIMA model were 0.4467 and 0.6521 in training part, and 0.0958 and 0.1133 in validation part, respectively. The mean absolute error and mean absolute percentage error of the hybrid model were also less than the ARIMA model. Discussion and Conclusions The gradual decline in tuberculosis report rate may be attributed to the effect of intensive measures on tuberculosis. The striking seasonal variation may have resulted from several factors. We suppose that a delay in the surveillance system may also have contributed to the variation. According to the fitting and prediction accuracy, the hybrid model outperforms the traditional ARIMA model, which may facilitate the allocation of health resources in China.