Abstract Objective: The objective was to evaluate whether initiation of urate-lowering treatment (ULT) during an acute gout flare prolonged the current episode. Methods: A comprehensive search of MEDLINE and Web of Science databases was conducted from their inception to 15 March 2021. Five randomized controlled trials (RCTs) with 381 patients met the inclusion criteria. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were used for estimating the clinical efficacy of ULT in acute gout. Results: There was no statistical difference in days to resolution (intent-to-treat analysis) (SMD, 0.68; 95% CI — 0.42 to 1.78; I2, 49%; p = 0.22), the pain visual analogue score (VAS) by day 10 (SMD, — 0.07; 95% CI — 0.30 to 0.16; I2, 0%; p = 0.53), C-reactive protein (CRP) from day 7 to 10 (SMD, — 1.14; 95% CI — 5.63 to 3.36; I2, 55%; p = 0.62), erythrocyte sedimentation rate (ESR) from day 7 to 10 (SMD, — 2.51; 95% CI — 5.46 to 0.45; I2, 0%; p = 0.10) and the recurrence of gout flares within 28-30 days (OR 0.78; 95% CI 0.29 to 2.09; I2, 0%; p = 0.62). Conclusion: Initiation of ULT during an acute gout flare did not prolong the duration of the flare. However, larger sample size studies are needed to confirm this finding. Trial registration number PROSPERO (CRD42021234581).

RESUMO Objetivo: Com o aumento do número e da juventude dos pacientes com espondilose cervical, as pessoas prestam cada vez mais atenção à coluna cervical. O diagnóstico, intervenção e tratamento precoces desempenham um papel importante na recuperação da espondilose cervical. Com o desenvolvimento contínuo da tecnologia computacional, o aprimoramento de várias teorias de modelagem e a aplicação de métodos de processamento de imagens na ortopedia, novas ideias se abrem para observar a saúde do movimento das vértebras cervicais. Métodos: Neste trabalho, a mensuração do movimento cervical é realizada por meio de visão artificial. É proposto um método de medição de parâmetro baseado na taxa de restrição de movimento cervical inferior. Com base no pré-processamento da imagem, a borda esquerda da vértebra cervical foi extraída e analisada. Resultados: Com a coordenada horizontal do ponto de registro como linha de referência, a tendência de mudança do ângulo entre a curva da borda esquerda e a linha de referência das vértebras C4 e C5 foi observada no processo de flexão espontânea e extensão do vértebras, vértebras cervicais e a taxa de movimento das vértebras cervicais. Conclusões: Verificou-se que a velocidade das vértebras cervicais no processo de movimentação de pacientes com espondilose cervical apresentou alterações de salto. Nível de evidência II; Estudos terapêuticos- investigação dos resultados do tratamento.

ABSTRACT Objective: With the increasing number and youth of patients with cervical spondylosis, people pay more and more attention to the cervical spine. Early diagnosis, intervention and treatment play an important role in the recovery of cervical spondylosis. With the continuous development of computer technology, the improvement of various modeling theories, and the application of image processing methods in orthopedics, new ideas are opened to observe cervical vertebra motion health. Methods: In this paper, the measurement of cervical motion is achieved by machine vision. A method of parameter measurement based on the constraint relationship of lower cervical motion is proposed. Based on image preprocessing, the left edge of the cervical vertebra was extracted and analyzed. Results: With the horizontal coordinate of registration point as the reference line, the changing trend of the angle between the left edge curve and the reference line of C4 and C5 vertebrae in the process of spontaneous flexion and extension of the cervical vertebrae was observed, and the movement rate of the cervical vertebrae was analyzed. Conclusions: It was found that the speed of the cervical vertebrae in the process of movement of the patients with cervical spondylosis showed jumping changes. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMEN Objetivo: Con el número creciente y la juventud de pacientes con espondilosis cervical, las personas prestan cada vez más atención a la columna cervical. El diagnóstico, la intervención y el tratamiento tempranos juegan un papel importante en la recuperación de la espondilosis cervical. Con el desarrollo continuo de la tecnología informática, la mejora de varias teorías de modelado y la aplicación de métodos de procesamiento de imágenes en ortopedia, se abren nuevas ideas para observar la salud del movimiento de las vértebras cervicales. Métodos: En este trabajo, la medición del movimiento cervical se logra mediante visión artificial. Se propone un método de medición de parámetros basado en la relación de restricción del movimiento cervical inferior. Sobre la base del preprocesamiento de imágenes, se extrajo y analizó el borde izquierdo de la vértebra cervical. Resultados: Con la coordenada horizontal del punto de registro como línea de referencia, se observó la tendencia cambiante del ángulo entre la curva del borde izquierdo y la línea de referencia de las vértebras C4 y C5 en el proceso de flexión y extensión espontánea de las vértebras cervicales, y Se analizó la tasa de movimiento de las vértebras cervicales. Conclusiones: Se encontró que la velocidad de las vértebras cervicales en el proceso de movimiento de los pacientes con espondilosis cervical mostró cambios de salto. Nivel de evidencia II; Estudios terapéuticos- investigación de los resultados del tratamiento.

RESUMO OBJETIVO Tendo em vista a alta incidência de síndrome dos ovários policísticos (SOP) e os efeitos terapêuticos insatisfatórios da dimetildiguanida ou do citrato de clomifeno isoladamente, nosso estudo teve como objetivo investigar os efeitos terapêuticos da dimetildiguanida associada ao citrato de clomifeno no tratamento da SOP. MÉTODOS Um total de 79 pacientes com POCS e 35 mulheres saudáveis foram incluídos, e biópsias endometriais foram obtidas. A expressão da proteína de ligação do elemento regulador de esterol-1 (SREBP1) nos tecidos endometriais foi detectada por qRT-PCR. Pacientes POC foram divididos aleatoriamente em grupo A (n=40) e grupo B (n=39). Os pacientes do grupo A foram tratados com dimetildiguanida combinada com citrato de clomifeno, enquanto os pacientes do grupo B foram tratados apenas com citrato de clomifeno. O número de folículos maduros e muco cervical, taxa de desenvolvimento folicular e taxa de ovulação, taxa de gravidez, abortamento precoce, taxa de ovulação, espessura endometrial, taxa positiva de três linhas, nível de hormônio folículo estimulante e nível de hormônio luteinizante foram comparados entre os dois grupos. RESULTADOS O nível de expressão do SREBP1 foi maior nos pacientes com SOP do que no controle normal. A expressão de SREBP1 foi inibida após o tratamento, enquanto os efeitos inibidores do tratamento combinado foram mais fortes do que os do citrato de clomifeno isoladamente. Comparado com o citrato de clomifeno sozinho, o tratamento combinado melhorou significativamente a pontuação do muco cervical, a taxa de desenvolvimento folicular, a taxa de ovulação do folículo único, a espessura endometrial, a taxa positiva de três linhas de sinal e o nível de hormônio folículo estimulante. CONCLUSÃO O efeito terapêutico do tratamento combinado é melhor do que o citrato de clomifeno isolado no tratamento da SOP.

SUMMARY OBJECTIVE In view of the high incidence of polycystic ovary syndrome (PCOS) and the unsatisfactory therapeutic effects of dimethyldiguanide or clomifene citrate alone, our study aimed to investigate the therapeutic effects of dimethyldiguanide combined with clomifene citrate in the treatment of PCOS. METHODS A total of 79 patients with POCS and 35 healthy females were included, and endometrial biopsies were obtained. The sterol regulatory element-binding protein-1 (SREBP1) expression in endometrial tissues was detected by qRT-PCR. POC patients were randomly divided into group A (n=40) and group B (n=39). Patients in group A were treated with dimethyldiguanide combined with clomifene citrate, while patients in group B were treated with clomifene citrate alone. The number of mature follicles and cervical mucus score, follicular development rate and single follicle ovulation rate, cycle pregnancy rate, early miscarriage rate, ovulation rate, endometrial thickness, positive rate of three lines sign, follicle stimulating hormone level and luteinizing hormone level were compared between the two groups. RESULTS The expression level of SREBP1 was higher in PCOS patients than that in the healthy control. SREBP1 expression was inhibited after treatment, while the inhibitory effects of combined treatment were stronger than those of clomifene citrate alone. Compared with clomifene citrate alone, the combined treatment improved cervical mucus score, follicle development rate, single follicle ovulation rate, endometrial thickness, positive rate of three lines sign, and follicle-stimulating hormone level. CONCLUSION The therapeutic effect of combined treatment is better than clomifene citrate alone in the treatment of PCOS.

ABSTRACT Antiviral drug resistance is the most important factor contributing to treatment failure using nucleos(t)ide analogs such as lamivudine for chronic infection with hepatitis B virus (HBV). Development of a system supporting efficient replication of clinically resistant HBV strains is imperative, and new antiviral drugs are needed urgently to prevent selection of drug-resistant HBV mutants. A novel fluorinated cytidine analog, NCC (N-cyclopropyl-4′-azido-2′-deoxy-2′-fluoro-β-d-cytidine), was recently shown to strongly inhibit human HBV in vitro and in vivo. This study was designed to evaluate the antiviral activity of NCC against lamivudine-resistant HBV. We generated a stable cell line encoding the major pattern of lamivudine-resistant mutations rtL180M/M204V and designated it "HepG2.RL1". Immuno-transmission electron microscopic examination and enzyme-linked immunosorbent assay were used to detect secretion of HBV-specific particles and antigens. Quantification of extracellular DNA and intracellular DNA of HepG2.RL1 cells by quantitative real-time polymerase chain reaction revealed >625-fold and >5556-fold increases in the 50% inhibitory concentration of lamivudine, respectively, compared with that for the wild-type virus. The results showed that NCC inhibited DNA replication and HBeAg production in wild-type or lamivudine-resistant HBV in a dose-dependent manner. In conclusion, screening for antiviral compounds active against lamivudine-resistant HBV can be carried out with relative ease using hepG2.RL1 cells. NCC is a potential antiviral agent against wild-type HBV and clinical lamivudine-resistant HBV and deserves evaluation for the treatment of HBV infection.

Background and Objectives: Schizophrenia is a severe chronic disease. Endpoint variables lack objectivity and the diagnostic criteria have evolved with time. In order to guide the development of new drugs, European Medicines Agency (EMA) issued a guideline on the clinical investigation of medicinal products for the treatment of schizophrenia. Methods: Authors reviewed and discussed the efficacy trial part of the Guideline. Results: The Guideline divides clinical efficacy trials into short-term trials and long-term trials. The short-term three-arm trial is recommended to replace the short-term two-arm active-controlled non-inferiority trial because the latter has sensitivity issues. The Guideline ultimately makes that three-arm trial a superiority trial. The Guideline discusses four types of long-term trial designs. The randomized withdrawal trial design has some disadvantages. Long-term two-arm active-controlled non-inferiority trial is not recommended due to the sensitivity issue. Extension of the short-term trial is only suitable for extension of the short-term two-arm active-controlled superiority trial. The Guideline suggests that a hybrid design of a randomized withdrawal trial incorporated into a long-term parallel trial might be optimal. However, such a design has some disadvantages and might be too complex to be carried out. Authors suggest instead a three-group long-term trial design, which could provide comparison between test drug and active comparator along with comparison between the test drug and placebo. This alternative could arguably be much easier to carry out compared with the hybrid design. Conclusions: The three-group long-term design merits further discussion and evaluation.