RESUMO Introdução: O salto vertical é inerente à prática do salto em altura e demanda grande capacidade de geração de força e trabalho da muscular do joelho, principalmente do músculo quadríceps. Devido a esta demanda, desequilíbrios entre os músculos extensores e flexores podem estar presentes, levando à sobrecarga das estruturas musculotendíneas da articulação do joelho. Sendo assim, torna-se necessário o estabelecimento das características da força muscular isocinética na articulação do joelho desses atletas. Objetivo: Este estudo teve como objetivo analisar as propriedades biomecânicas dos músculos flexores e extensores do joelho nos atletas de salto em altura. Métodos: Dez saltadores voluntariaram-se para o experimento. Eles foram divididos em grupos experimentais e grupos de controle. Ambos os grupos realizaram o treinamento básico de força. O grupo experimental adicionou treinamento muscular isocinético do joelho baseado neste treinamento. Foram realizadas análises estatísticas sobre os dados de treinamento dos dois grupos de atletas, utilizando estatísticas matemáticas pertinentes. Resultados: O salto em altura consiste de quatro fases, sendo respectivamente a corrida de aproximação, o salto em si (impulsão, elevação, transposição) e a queda. A força da dorsiflexão da articulação do tornozelo e dos flexores plantares foi significativamente aumentada no grupo experimental de atletas. Em contraste, somente a força dos flexores plantares no grupo de controle foi significativamente aumentada. Foram encontradas diferenças estatísticas entre os dois grupos (P<0,05). Conclusão: O modo de treinamento de força isocinética da articulação do joelho pode melhorar a força de apoio nas pernas dos saltadores. Este artigo sugere que os atletas de salto em altura podem adotar mais este método para o treinamento de força para membros inferiores. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

ABSTRACT Introduction: Vertical jump is inherent to the practice of high jump and demands great capacity of force generation and work of the knee muscles, especially the quadriceps muscle. Due to this demand, imbalances between the extensor and flexor knee muscles may be present, leading to an overload of the musculotendinous structures of the knee joint. Therefore, it is necessary to establish the characteristics of isokinetic muscle strength in the knee joint of these athletes. Objective: This study aimed to analyze the biomechanical properties of the knee flexor and extensor muscles in high jump athletes. Methods: Ten high jumpers volunteered for the experiment. They were divided into experimental and control groups. Both groups performed basic strength training. The experimental group added isokinetic knee muscle training based on this training. Statistical analyses were performed on the training data of the two groups of athletes using relevant mathematical statistics. Results: The high jump consists of four phases being respectively the approach run, the jump itself (impulsion, elevation, transposition), and the fall. The strength of the ankle joint dorsiflexion and plantar flexors was significantly increased in the experimental group of athletes. In contrast, the strength of the plantar flexors in the control group was significantly increased. Statistical differences were found between the two groups (P<0.05). Conclusion: The isokinetic knee joint strength training mode can improve the leg support strength of jumpers. This paper suggests that high jump athletes can further adopt this lower limb strength training method. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMEN Introducción: El salto vertical es inherente a la práctica del salto de altura y exige una gran capacidad de generación de fuerza y trabajo de los músculos de la rodilla, principalmente del cuádriceps. Debido a esta demanda, puede haber desequilibrios entre los músculos extensores y flexores, lo que lleva a la sobrecarga de las estructuras musculotendinosas de la articulación de la rodilla. Por lo tanto, es necesario establecer las características de la fuerza muscular isocinética en la articulación de la rodilla de estos atletas. Objetivo: El propósito de este estudio fue analizar las propiedades biomecánicas de los músculos flexores y extensores de la rodilla en atletas de salto de altura. Métodos: Diez saltadores de altura se ofrecieron como voluntarios para el experimento. Se dividieron en grupos experimentales y de control. Ambos grupos realizaron un entrenamiento de fuerza básico. El grupo experimental añadió un entrenamiento muscular isocinético de la rodilla basado en este entrenamiento. Se realizaron análisis estadísticos de los datos de entrenamiento de los dos grupos de atletas utilizando las estadísticas matemáticas pertinentes. Resultados: El salto de altura consta de cuatro fases, que son respectivamente la carrera de aproximación, el salto propiamente dicho (impulsión, elevación, transposición) y la caída. La fuerza de la dorsiflexión de la articulación del tobillo y de los flexores plantares aumentó significativamente en el grupo experimental de atletas. Por el contrario, sólo aumentó significativamente la fuerza de los flexores plantares en el grupo de control. Se encontraron diferencias estadísticas entre los dos grupos (P<0,05). Conclusión: El modo de entrenamiento isocinético de la fuerza de la articulación de la rodilla puede mejorar la fuerza de apoyo de la pierna en los saltadores. Este artículo sugiere que los atletas de salto de altura pueden adoptar este método para el entrenamiento de la fuerza de las extremidades inferiores. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Abstract Introduction: Long QT Syndrome (LQTS) is an inherited disease with an abnormal electrical conduction system in the heart that can cause sudden death as a result of QT prolongation. LQT2 is the second most common subtype of LQTS caused by loss of function mutations in the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene. Although more than 900 mutations are associated with the LQTS, many of these mutations are not validated or characterized. Methods and results: Sequencing analyses of genomic DNA of a family with LQT2 identified a putative mutation. i.e., KCNH2(NM_000238.3): c.3099_3112del, in KCNH2 gene which appeared to be a definite pathogenic mutation. The family pedigree information showed a gender difference in clinical features and T-wave morphology between male and female patients. The female with mutation exhibited recurring ventricular arrhythmia and syncope, while two male carriers did not show any symptoms. In addition, T-wave in females was much flatter than in males. The female proband showed a positive reaction to the lidocaine test. Lidocaine injection almost completely blocked ventricular arrhythmia and shortened the QT interval by ≥30 ms. Treatment with propranolol, mexiletine, and implantation of cardioverter-defibrillators prevented the sustained ventricular tachycardia, ventricular fibrillation, and syncope, as assessed by a 3-year follow-up evaluation. Conclusions: A putative mutation c.3099_3112del in the KCNH2 gene causes LQT2 syndrome, and the pathogenic mutation mainly causes symptoms in female progeny. Introduction (LQTS prolongation LQT voltagegated voltage gated KCNH (KCNH2 90 characterized results ie i e i.e. KCNH2NM_000238.3 KCNH2NM0002383 KCNHNM NM_000238.3 NM 000238 3 KCNH2(NM_000238.3) c30993112del cdel c 3099 3112del del Twave T wave patients syncope addition males test 30 ≥3 ms propranolol mexiletine cardioverterdefibrillators cardioverter defibrillators tachycardia fibrillation 3year year followup follow up evaluation Conclusions syndrome progeny (KCNH 9 i.e KCNH2NM KCNH2NM_000238. KCNH2NM000238 NM0002383 NM_000238. 00023 KCNH2(NM_000238.3 309 ≥ KCNH2NM_000238 KCNH2NM00023 NM000238 NM_000238 0002 KCNH2(NM_000238. KCNH2NM_00023 KCNH2NM0002 NM00023 NM_00023 000 KCNH2(NM_000238 KCNH2NM_0002 KCNH2NM000 NM0002 NM_0002 00 KCNH2(NM_00023 KCNH2NM_000 KCNH2NM00 NM000 NM_000 0 KCNH2(NM_0002 KCNH2NM_00 KCNH2NM0 NM00 NM_00 KCNH2(NM_000 KCNH2NM_0 NM0 NM_0 KCNH2(NM_00 KCNH2NM_ NM_ KCNH2(NM_0 KCNH2(NM_ KCNH2(NM

ABSTRACT Purpose: To investigate the effect of genistein on inflammation and mitochondrial function of diabetic nephropathy. Methods: Diabetic nephropathy model was established in Sprague-Dawley rats. Automatic biochemical analyzer was employed to detect the kidney function index, serum creatinine, serum urea nitrogen, and 24 h-urine protein and blood glucose. Hematoxylin and eosin staining and periodic acid Schiff staining were used to observe renal morphology. Mitochondrial changes and podocyte integrity were monitored by transmission electron microscope. The expression levels of mfn2, NOX4, P53, MAPK, and NF-κB were detected by Western blotting. The changes of mitochondrial membrane potential were measured by JC-1. The level of mfn2 was assessed by immunofluorescence assay. Results: Genistein ameliorated the kidney function with reduced Scr and blood glucose. The expressions of NOX4, MAPK, p65 and p53 were downregulated, while the expression of mnf2 was the opposite in genistein-treated kidneys. Further investigations revealed that genistein reduced expansion of mesangial matrix and oxidative stress, protected podocyte integrity and increased mitochondrial membrane potential. Conclusions: Genistein could alleviate diabetic nephropathy through inhibiting MAPK/NF-κB pathway, improving mitochondrial function and anti-inflammatory.

OBJECTIVES: This study was designed to evaluate the clinical efficacy of controlled-release morphine tablets combined with celecoxib in relieving osteocarcinoma-related pain and the effects of the combination on WNK1 expression. METHODS: A total of 110 patients with osteocarcinoma-related pain were selected and divided into two groups based on the treatment administered, including the control group (treated with controlled-release morphine tablets alone) and the study group (treated with a combination of controlled-release morphine tablets and celecoxib). We compared the treatment efficacy, pain level (visual analog scale (VAS)), time of onset of breakthrough pain (BTP), dose of morphine, incidence of adverse events, quality of life (QOL) score, and With-no-lysine 1 (WNK1) expression in the peripheral blood (PB) as determined with qRT-PCR before and after treatment, of the two groups. RESULTS: The total effective rate of the study group was higher than that of the control group, while the VAS score, time of onset of BTP, dose of morphine, incidence of adverse events, QOL score, and relative WNK1 expression in the PB were lower than those of the control group (p<0.05). CONCLUSION: Combination treatment with controlled-release morphine tablets and celecoxib can be extensively used in the clinical setting because it effectively improves the symptoms, QOL score, and adverse effects in patients with osteocarcinoma-related pain.

2-Methyl-2-butanol (MBT) is a chemical compound from the group of alcohols more specifically pentanols, which has shown an excellent anti-cancer activity in our previous study. However, its mechanism of action remains unclear. The present study was designed to investigate the anti-cancer effect of MBT on human retinoblastoma cells. The results showed that the use of MBT leads to HXO-RB44 cell death but is cytotoxic to normal cells at higher concentrations. It showed a dose- as well as a time-dependent inhibition of HXO-RB44 cells. P27 is a cell cycle inhibitory protein, which plays an important role in cell cycle regulation whereas cyclin-B1 is a regulatory protein involved in mitosis. MBT increased the cell cycle arrest in a dose-dependent manner by augmenting p27 and reducing cyclin B1 expression. Moreover, it also accelerated apoptosis, increased light chain-3 (LC-3) conversion in a dose-dependent manner, and helped to debulk cancerous cells. LC3 is a soluble protein, which helps to engulf cytoplasmic components, including cytosolic proteins and organelles during autophagy from autophagosomes. In order to verify the effect of MBT, bafilomycin A1, an autophagy inhibitor, was used to block the MTB-induced apoptosis and necrosis. Additionally, a specific Akt agonist, SC-79, reversed the MBT-induced cell cycle arrest and autophagy. Thus, from the present study, it was concluded that MBT induced cell cycle arrest, apoptosis and autophagy through the PI3K/Akt pathway in HXO-RB44 cells.

Background and Objectives: Tryptophan hydroxylase 2 (TPH2) catalyzes the rate-limiting step in serotonin biosynthesis in the nervous system. Several variants of human TPH2 have been reported to be associated with a spectrum of neuropsychiatric disorders such as unipolar major depression, bipolar disorder and suicidality etc. Recent studies suggested that two variants (T212 and A375) in the exon 7 and exon 9 were associated with major depressive disorder (MDD). Methods: To replicate these findings, two polymorphisms located in exons 7 and 9 of TPH2 (rs7305115 and rs4290270, respectively) were analysed by DNA sequence in the case-control sample study in 191 MDD and 191 healthy volunteers. Statistical analyses were carried out using the program SPSS. The comparison of allele and genotype frequencies of each polymorphism between case and control groups was carried out on the online software SHEsis. All subjects were unrelated southern Han Chinese. Results: No difference was observed on the allelic or genotypic distribution of TPH2 gene polymorphisms between the groups. However, the two-marker haplotype covering components T212 (rs7305115) A and A375 (rs4290270) T were observed to have a significantly protective effect MDD in female (corrected p = 0.0032; OR = 0.241[95% CI = 0.099-0.587]). Conclusions: The results suggest that TPH2 might be associated with a lower risk of female MDD. However, confirmatory studies in independent samples are needed.

Abstract Objective There are a lot of disagreements in the studies on hepatitis B virus (HBV) DNA polymerase mutation rate associated with nucleos(t)ide analogues (NAs) in treatment-naive chronic hepatitis B (CHB) patients. This is the first study aimed to investigate the prevalence of spontaneous HBV resistance mutations in Central China. Methods This study included treatment-naive patients with CHB from June 2012 to May 2015 receiving care at the Institute of Liver Disease in Central China. All patients completed a questionnaire covering different aspects, such as family medical history, course of liver disease, medication history, alcohol use, among others. Mutations in HBV DNA polymerase associated with NAs resistance were detected using INNO-LiPA assay. Results 269 patients were infected with HBV genotype B (81.4%), C (17.9%), and both B and C (0.7%). Mutations in HBV DNA polymerase were detected in 24 patients (8.9%) including rtM204I/V (n = 6), rtN236T (n = 5), rtM250V (n = 2), rtL180M (n = 2), rtT184G (n = 1), rtM207I (n = 1), rtS202I (n = 1), rtM204V/I & rtL180M (n = 5), and rtM204I & rtM250V (n = 1). Conclusion Spontaneous HBV resistance mutations in HBV DNA polymerase were found in treatment-naive patients with CHB in Central China. These findings suggest that we should analyze HBV DNA polymerase resistance mutation associated with NAs before giving antiviral therapy such as lamivudine (LAM), adefovir (ADV), and telbivudine (LdT).

Background: WNT4 is a protein that plays a crucial role in ovarian differentiation and development in mammals, with a relatively well understood function in mammalian gonadal differentiation. The role of WNT4 in teleost fish; however, remains unclear. In the present study, cDNAs of Wnt4a and Wnt4b were cloned and characterized in the spotted scat. The expression patterns of two Wnt4 genes in the gonads at different stages of development and in fish after treatment with 17a-methyltestosterone (MT) were investigated. Results: The tissue distribution showed that Wnt4a was expressed in various tissues, including the gonads, gills, spleen, brain, and fin. Interestingly, Wnt4b not only was expressed in the gills, brain, and spleen, but also was obviously expressed in the ovary. During gonad development, Wnt4a was highly expressed in the testis at stage I and Wnt4b was mainly expressed in the ovary at stages II-III. After MT treatment, the mRNA expression of Wnt4a increased significantly up to 40 d, and the transcript level of Wnt4b decreased at 20 d. Conclusions: These results suggest that Wnt4a may be involved in gonad development and plays a role in the process of spermatogonial proliferation. Our results also demonstrate that Wnt4b is not only expressed in the nervous system, but also in the ovary and it may be involved in ovary development of the spotted scat.

A new inulinase-producing strain was isolated from rhizosphere soils of Jerusalem artichoke collected from Shihezi (Xinjiang, China) using Jerusalem artichoke power (JAP) as sole carbon source. It was identified as an Aspergillus niger strain by analysis of 16S rRNA. To improve inulinase production, this fungus was subjected to mutagenesis induced by 60Co γ-irradiation. A genetically stable mutant (designated E12) was obtained and it showed 2.7-fold higher inulinase activity (128 U/mL) than the parental strain in the supernatant of a submerged culture. Sequential methodology was used to optimize the inulinase production of stain E12. A screening trial was first performed using Plackett-Burman design and variables with statistically significant effects on inulinase bio-production were identified. These significant factors were further optimized by central composite design experiments and response surface methodology. Finally, it was found that the maximum inulinase production (185 U/mL) could be achieved under the optimized conditions namely pH 7.0, yeast extract concentration of 5.0 g/L, JAP concentration of 66.5 g/L, peptone concentration of 29.1 g/L, solution volume of 49.4 mL in 250-mL shake flasks, agitation speed of 180 rpm, and fermentation time of 60 h. The yield of inulinase under optimized culture conditions was approximately 1.4-fold of that obtained by using basal culture medium. These findings are of significance for the potential industrial application of the mutant E12.

An incompressible fully developed laminar flow in a helical rectangular duct having finite pitch and curvature with temperature-dependent viscosity under heating condition is studied in this work. Both the cases of one wall heated and four walls heated are studied. The cross-sectional dimensions of the rectangular duct are 2a and 2b. The aspect ratio n=2b/2a is 0.5. Water is used as the fluid and Reynolds number (Re) is varied in the range of 100 to 400. The secondary flow with temperature-dependent viscosity is enhanced markedly as compared to constant viscosity. An additional pair of vortices is obtained near the center of the outer wall at Re=400 for the model of four walls heated with temperature-dependent viscosity, y, while for constant viscosity, the appearance of two additional vortices near the outer wall cannot be found. Besides, the axial velocity decreases and the temperature increases at the central region of the rectangular duct when the temperature-dependent viscosity is considered. Due to the decrease of the viscosity near the walls, the friction factor obtained with temperature-dependent viscosity is lower than that of constant viscosity, while the convective heat transfer for temperature-dependent viscosity is significantly enhanced owing to the strengthened secondary flow. Especially for four heated walls, the effects of viscosity variation on the flow resistance and heat transfer are more significant.

Análisis estadísticos, un diagrama de Piper, el índice de saturación y la correlación de los parámetros químicos fueron utilizados para revelar la hidrogeoquímica y la evolución hidrogeoquímica de las aguas subterráneas poco profundas en la parte sur de la sección Zhongwei en la planicie aluvial del río Amarillo. La calidad del agua para el uso doméstico y agrícola también fue evaluada en este estudio. Los resultados sugieren que las aguas subterráneas poco profundas en el área de estudio son entre frescas y moderadamente mineralizadas. Un índice mayor de Ca2+ y HCO3- se observó en las aguas menos mineralizadas, mientras que Na+ y SO4(2-) son iones comunes en las aguas altamente mineralizadas. Los perfiles hidroquímicos predominantes para las aguas subterráneas con Total de Sólidos Disueltos (TDS) <1 g/L son HCO3-Ca·Mg y HCO3-Ca·Na·Mg, y para las aguas subterráneas con TDS >1 g/L, SO4·Cl-Na y SO4·Cl-Na·Mg·Ca. Las mayores reacciones en el sistema de aguas subterráneas son la disolución/precipitación de yeso, fluorita, halita, calcita y dolomita. El intercambio de cationes también es importante en el control de la química de las aguas subterráneas. Las muestras de agua evaluadas en este manuscrito son de calidad aceptable para el uso agrícola, pero la mayoría no son aptas para el consumo humano. El índice TDS, la dureza total del agua (TH), Cl- y SO4(2-) son las razones principales que influyen en la baja calidad de esta agua.

Statistical analyses, a Piper diagram, the saturation index and the correlations of chemical parameters were used to reveal the hydrogeochemistry and hydrogeochemical evolution of shallow groundwater in the southern part of the Zhongwei section of the Yellow River alluvial plain. The water quality for agricultural and domestic uses was also assessed in the study. The results suggest that the shallow groundwater in the study area is fresh to moderately mineralized water. Higher Ca2+ and HCO3- are observed in the less mineralized water, whereas Na+ and SO4(2-) are common ions in the highly mineralized water. The major hydrochemical facies for groundwater with total dissolved solids (TDS) <1 g/L are HCO3-Ca·Mg and HCO3-Ca·Na·Mg, and for groundwater with TDS > 1 g/L, SO4 ·Cl-Na and SO4·Cl-Na·Mg·Ca are the predominant hydrochemical types. The main reactions in the groundwater system are the dissolution/precipitation of gypsum, fluorite, halite, calcite and dolomite. Cation exchange is also important in controlling the groundwater chemistry. The water samples assessed in the paper are of acceptable quality for agricultural use, but most of them are not fit for direct human consumption (drinking). TDS, total hardness (TH), Cl- and SO4(2-) are the main indices that result in the poor drinking water quality.

PROBLEM: China's National Methadone Maintenance Treatment Programme (MMT) has expanded from eight clinics serving approximately 1000 clients to 738 clinics that have served more than 340 000 clients cumulatively in only 8 years. This has created an enormous demand for trained providers. APPROACH: Human resource development and capacity building efforts have been conducted in China's National MMT Programme to create a supply of providers trained in administering MMT for opioid dependence. LOCAL SETTING: From 2004 to 2007, China's National MMT Programme faced several problems: inappropriately low methadone doses, poor compliance, high concurrent drug use and high drop-out rates among clients, and little experience, little training and high turnover rates among providers. RELEVANT CHANGES: Training programmes for individual providers and their trainers were redeveloped and expanded in 2008. Although programme performance metrics show an increase in patients' annual mean duration in treatment (93 days in 2004 versus 238 days in 2011), the increase in their mean daily methadone dose (from 47.2 mg in 2004 to 58.6 mg in 2011) is modest. LESSONS LEARNT: Some of the problems that can arise during the development, launch and scale-up of a major national public health effort, such as China's National MMT Programme, cannot be foreseen. Key to the programme's success so far have been the strong commitment on the part of China's government and the optimism and pragmatism of programme managers. Human resources development and capacity-building during scale-up have contributed to improved service quality in MMT treatment clinics and are critical to long-term success.

SITUACIÓN: El Programa Nacional para el Tratamiento de Mantenimiento con Metadona de China ha pasado de tener ocho clínicas que atendían a aproximadamente 1000 clientes a 738 clínicas con un total acumulado de más de 340 000 clientes atendidos en sólo ocho años, lo que ha creado una demanda enorme de proveedores de servicios cualificados. ENFOQUE: Los esfuerzos para el desarrollo de los recursos humanos y la creación de capacidad adecuada han llevado al Programa Nacional para el TMM de China a crear un programa para aportar proveedores cualificados capaces de administrar el tratamiento de mantenimiento con metadona (TMM) para la dependencia de opiáceos. MARCO REGIONAL: Desde el año 2004 hasta el 2007, el Programa Nacional para el TMM chino tuvo que hacer frente a numerosos problemas: dosis inadecuadamente bajas de metadona, cumplimiento deficiente del programa, elevado uso simultáneo de drogas, tasas altas de abandono entre los clientes, falta de experiencia y de formación, así como índices elevados de rotación entre los proveedores de servicios. CAMBIOS IMPORTANTES: En el año 2008 se volvieron a diseñar y se aumentaron los programas de formación para los proveedores individuales, así como para sus instructores. Aunque las mediciones del rendimiento del programa muestran un aumento de la duración media anual del tratamiento de los pacientes (93 días en 2004 frente a 238 días en 2011), el aumento de la dosis diaria de metadona (de 47,2 mg en 2004 a 58,6 mg en 2011) resulta moderado. LECCIONES APRENDIDAS: No es posible prever todos los problemas que pueden surgir durante el desarrollo, el lanzamiento y la expansión de un esfuerzo de tal relevancia en materia de salud pública nacional como es el Programa chino para el Tratamiento de Mantenimiento con Metadona. Las claves para el éxito del programa han sido, hasta ahora, el fuerte compromiso por parte del gobierno chino, así como el optimismo y el pragmatismo de los gestores del programa. El desarrollo de los recursos humanos y la creación de capacidad durante su proceso de expansión han contribuido a mejorar la calidad del servicio en las clínicas de TMM y son fundamentales para el éxito a largo plazo.

PROBLÈME: Le programme national chinois de traitement de maintien à la méthadone est passé de 8 hôpitaux traitant environ 1 000 patients à 738 cliniques qui ont suivi plus de 340 000 patients au total en seulement 8 ans. Cela a généré une énorme demande en prestataires expérimentés. APPROCHE: Le développement des ressources humaines et des efforts de renforcement des compétences ont été menés par le programme national chinois de traitement de maintien à la méthadone (TMM) afin de proposer des prestataires formés à la gestion du TMM en termes de dépendance aux opiacés. ENVIRONNEMENT LOCAL: De 2004 à 2007, le programme national chinois de TMM s'est heurté à divers problèmes: doses de méthadone inadéquatement faibles, observance médiocre, importante consommation simultanée de drogues et taux d'abandon élevés chez les patients, faible expérience et taux de renouvellement élevé des prestataires. CHANGEMENTS SIGNIFICATIFS: Des programmes de formation pour les prestataires et leurs formateurs ont été élaborés et développés en 2008. Bien que des mesures de performance du programme montrent une augmentation de la durée moyenne annuelle du traitement des patients (93 jours en 2004 pour 238 jours en 2011), l'augmentation de leur dose quotidienne moyenne de méthadone est modeste (de 47,2 mg en 2004 à 58,6 mg en 2011). LEÇONS TIRÉES: Certains problèmes qui peuvent survenir lors du développement, du lancement et de l'application à grande échelle d'un effort national majeur dans le domaine de la santé publique, tel que le programme national chinois du traitement de maintien à la méthadone, ne peuvent être prévus. À ce jour, les clés du succès du programme sont l'engagement marqué de la part du gouvernement chinois ainsi que l'optimisme et le pragmatisme des responsables du programme. Le développement des ressources humaines et le renforcement des compétences lors du développement à grande échelle ont contribué à une amélioration de la qualité du service dans les cliniques de TMM et sont essentiels pour une réussite à long terme.

We develop the impulsive inequality and the classical lower and upper solutions, and establish the comparison principles. By using these results and the monotone iterative technique, we obtain the existence of solutions of periodic boundary value problems for a class of impulsive neutral differential equations with multi-deviation arguments. An example is given to demonstrate our main results. Mathematical subject classification: Primary: 34A37; Secondary: 34k10.