Comparación de Latanoprostene bunod 0,024 % y Latanoprost 0,005 % en glaucoma de ángulo abierto e hipertensión ocular

Introducción: El glaucoma es la principal causa de ceguera irreversible en el mundo. La prevalencia mundial de glaucoma en personas de 40 a 80 años se estima en un 3,5 %. Objetivo: Comparar el efecto reductor de la PIO de Latanoprostene bunod (LBN) al 0,024% con Latanoprost al 0,005 % en sujetos con glaucoma de ángulo abierto (GAA) o hipertensión ocular (HTO). Metodología: Ensayo observacional de estudio de cohorte prospectivo. Resultados: Fue realizado en 28 pacientes (56 ojos) quienes fueron aleatorizados en 2 grupos paralelos (28 ojos por grupo), el grupo Latanoprost y el grupo LBN. En el grupo LBN la media de la PIO antes del tratamiento fue de 25,3 ± 6,6 mmHg y la media de la PIO luego de 1 mes de tratamiento fue de 16,5 ± 4,9 mmHg (p<0,05). En el grupo Latanoprost la media de la PIO antes del tratamiento fue de 23,6 ± 3,6 mmHg y la media de la PIO luego de 1 mes de tratamiento con Latanoprost al 0,005% fue de 15,3 ± 2,4 mmHg (p<0,05). Sin embargo, al comparar las PIOs luego de 1 mes de tratamiento con LBN 0,024% y Latanoprost 0,005% se objetiva que la diferencia en reducción de la presión intraocular entre estos dos fármacos no fue significativa (p= 0,238). Discusión: Las prostaglandinas tópicas, con su potente efecto hipotensor ocular son una importante opción de tratamiento para el glaucoma. La reducción de la PIO es la esperada con ambos medicamentos, sin embargo, no existen diferencias significativas entre ambas luego de 1 mes de uso. Con respecto a los efectos secundarios, en el grupo LBN se encontró más efectos adversos oculares.

Introduction: Glaucoma is the main cause of irreversible blindness worldwide. The global prevalence of glaucoma in people aged 40 to 80 years is estimated at 3.5%. Objective: To compare the intraocular pressure (IOP) lowering effect of 0.024% Latanoprostene bunod (LBN) with 0.005% Latanoprost in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods: Observational trial of prospective cohort study. Results: It was performed in 28 patients (56 eyes) who were randomized into 2 parallel groups (28 eyes per group), the Latanoprost group and the Latanoprostene bunod (LBN) group. In the LBN group, the mean intraocular pressure before treatment was 25.3 ± 6.6 mmHg and the mean intraocular pressure after 1 month of treatment was 16.5 ± 4.9 mmHg (p<0,05). In the Latanoprost group, the mean intraocular pressure before treatment was 23.6 ± 3.6 mmHg and the mean intraocular pressure after 1 month of treatment with 0.005% Latanoprost was 15.3 ± 2.4 mmHg (p<0,05). However, when comparing the IOPs to the 1-month treatment with Latanoprostene bunod 0.024% and Latanoprost 0.005%, it is observed, through ANOVA, that the difference in intraocular pressure reduction between these two drugs is not significant (p= 0,238). Discussion: Topical prostaglandins, with their potent ocular hypotensive effect (resulting from increased uveoscleral outflow), are an important treatment option for glaucoma. The IOP reduction is as expected with both drugs, however, there are no significant differences between the two. In the LBN group, more drug-related ocular adverse effects were found after 1 month of use.

Patients in insulin analogues use via judicial litigation: do they use the Brazilian Public Health System (SUS)? / Pacientes em uso de análogos de insulina via ação judicial: eles utilizam o Sistema Único de Saúde (SUS)?

Abstract Background Studies show that among the drugs most commonly used in judicial litigation in Brazil, are those used to treat diabetes mellitus, especially insulin analogues. Objective Evaluate the use of the Unified Health System (SUS) by patients with type 1 diabetes mellitus (T1DM), who receive insulin analogues through judicial action, before and after this process. Method In a retrospective longitudinal observational study, secondary data was used from these patients in Minas Gerais, Brazil, in 2018. Socio-demographic information was collected and related to the follow-up of these patients in the SUS. The McNemar χ2 test was used to compare the proportions of the variables. Results Of the 89 patients analyzed, women (53.9%) were predominant. Most patients were aged between 20 and 39 years (52.8%), and more than half, 55.1%, use only a private health system. After the judicial action, there was a significant increase (p <0.05) in the number of patients who had consultations in primary health care (from 19.1% to 30.3%) and emergency medical appointments (from 1.1% to 9.0%). Conclusion It is observed that the majority of patients with T1DM via judicial action in the SUS are not monitored by this health system through examinations, consultations, and hospitalizations.

Resumo Introdução Estudos mostram que, dentre os medicamentos mais adquiridos via ação judicial, estão os utilizados para o tratamento do Diabetes Mellitus, especialmente os análogos de insulina. Objetivo Avaliar a utilização do Sistema Único de Saúde (SUS) pelos pacientes com Diabetes Mellitus tipo 1 (DM1), que recebem insulina por meio de judicialização, antes e após este processo. Método Em um estudo observacional longitudinal retrospectivo, foram utilizados dados secundários de pacientes com DM1, que adquiriram insulinas por processos judiciais em Divinópolis-MG, Brasil, em 2018. Foram coletadas informações sociodemográficas e referentes ao acompanhamento destes pacientes no SUS Realizou-se o teste χ2 de McNemar para a comparação das proporções das variáveis utilizadas para a avaliação do acompanhamento antes e após a judicialização. Resultados Dos 89 pacientes analisados, predominou-se o sexo feminino (53,9%), com idade entre 20 e 39 anos (52,8%). 55,1% destes utilizam apenas o sistema privado de saúde. Após a judicialização, houve um aumento significativo (p< 0,05) no número de pacientes que realizaram consultas na atenção primária à saúde (de 19,1% para 30,3%) e consultas médicas de emergência (de 1,1% para 9,0%). Conclusão A maioria dos pacientes com DM1 que judicializam medicamentos no SUS não são acompanhados por este sistema de saúde através de realização de exames, consultas e hospitalizações.

Establishment and application of hepatic organoid model of hepatitis B virus infection / 中华传染病杂志

Objective:To establish the hepatic organoid of hepatitis B virus (HBV) infection on the basis of induced pluripotent stem cells (iPSC) and an inverted colloidal crystal polyethylene glycol scaffold (ICC), and to evaluate the antiviral effect of nucleoside drugs.Methods:iPSC was differentiated into hepatocyte-like cells (HLC), and inoculated into ICC to construct a hepatic organoid. The relative mRNA expressions of Nanog homeobox (NANOG), sex determining region Y-box (SOX) 2, SOX17, forkhead box protein A2 (FOXA2), alpha fetoprotein (AFP) and albumin (ALB) were detected by real time quantitative polymerase chain reaction (RT-qPCR). Confocal laser microscopy was used to photograph the three-dimension (3D) structure of organs. The expression of sodium taurocholate cotransporting polypeptide (NTCP) in HLC was analyzed by Western blot and immunofluorescence. HepG2.2.15 cells were used to extract HBV virus particles to infect hepatic organoid. The relative expression of HBV pregenome RNA (pgRNA) in cells was detected by RT-qPCR. The expressions of hepatitis B core antigen (HBcAg) and hepatitis B surface antigen (HBsAg) in cytoplasm were observed under confocal laser microscopy. A total of 0.5 μmol/L entecavir and 0.5 μmol/L lamivudine were used to treat the infected cells respectively. The relative expression of HBV pgRNA in infected and uninfected cells was detected by RT-qPCR. Independent sample t test and one-way analysis of variance were used for statistical analysis. Results:Within 21 days of iPSC differentiation, the mRNA expressions of NANOG and SOX2 in stem cells markers decreased ( F=158.90 and 8.31, respectivley; P<0.001 and P=0.002, respectively), while the mRNA expressions of SOX17 and FOXA2 in the endoderm increased first and then decreased ( F=37.23 and 82.57, respectively, both P<0.001). In the later stage of differentiation, the mRNA expressions of AFP and ALB in liver cells increased ( F=4.65 and 34.64, respectively, P=0.012 and P<0.001, respectively), and all differences were statistically significant. NTCP was highly expressed in differentiated cells detected by Western blot and fluorescence microscopy, the protein expression level was 0.803±0.099. Confocal laser microscopy confirmed that the differentiated cells expressed ALB and presented spherical structure in ICC. The expression of HBV pgRNA and the immunostaining of HBsAg and HBcAg confirmed that HBV successfully infected hepatic organoid. Three days after the application of entecavir and lamivudine, the HBV pgRNA level decreased significantly both in entecavir group (0.665±0.220) and lamivudine group (0.503±0.117) compared to the uninfected cells (3.347±0.454), and the differences were both statistically significant ( t=10.53 and 12.72, respectively, both P<0.001). Conclusions:HLC display hepatic specific genes ALB and NTCP. Hepatic organoids constructed with iPSC and ICC have human liver function and can be infected by HBV. Entecavir and lamivudine could effectively inhibit the replication of HBV in hepatic organoids.

Advances in the effects of exposure to bisphenol A and its analogues during pregnancy on maternal and infant health / 国际儿科学杂志

Bisphenol A(BPA)as a typical environmental endocrine disruptor, has been widely used in daily consumer goods.It has reproductive, developmental, neurotoxicity and other biological toxicity, so it is gradually replaced by bisphenol F, bisphenol S, bisphenol AF and other analogues.Studies have shown that BPA and its analogues can enter the human body through many ways, have been detected in human blood, urine, placenta, breast milk, amniotic fluid and other tissue samples, and transmitted to the fetus, causing a variety of toxic effects, thus affecting the health of pregnant women and fetuses, and may lead to adverse pregnancy outcomes such as preterm delivery, abortion, low birth weight and so on.This article reviews the ways and current situation of exposure to BPA and its analogues during pregnancy in recent years, and its effects on maternal and fetal health, and puts forward reasonable suggestions for maternal and infant health from the point of view of exposure to adverse environmental factors, so as to provide inspiration for future research.

Demographic characteristics and associated influencing factors in treated patients with chronic hepatitis B with hypoviremia : a single-center retrospective cross-sectional study / 中华肝脏病杂志

Objective: To investigate the demographic characteristics and clinical influencing factors which associates with the occurrence probability of persistent or intermittent hypoviremia (LLV) in patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogues (NAs). Methods: A single-center retrospective analysis was performed on patients with CHB who received outpatient NAs therapy for≥48 ± 2 weeks. According to the serum hepatitis B virus (HBV) DNA load at 48±2 weeks treatment, the study groups were divided into LLV (HBV DNA < 20 IU/ml and < 2 000 IU/ml) and MVR group (sustained virological response, HBV DNA < 20 IU/ml). Demographic characteristics and clinical data at the start of NAs treatment (considered as baseline) were retrospectively collected for both patient groups. The differences in the reduction of HBV DNA load during treatment was compared between the two groups. Correlation and multivariate analysis were further conducted to analyze the associated factors influencing the LLV occurrence. Statistical analysis was performed using the independent samples t-test, c2 test, Spearman analysis, multivariate logistic regression analysis, or area under the receiver operating characteristic curve. Results: A total of 509 cases were enrolled, with 189 and 320 in the LLV and MVR groups, respectively. Compared to patients with MVR group at baseline: (1) the demographics characteristics of patients showed that LLV group was younger in age (39.1 years, P = 0.027), had a stronger family history (60.3%, P = 0.001), 61.9% received ETV treatment, and higher proportion of compensated cirrhosis (20.6%, P = 0.025) at baseline; (2) the serum virological characteristics of patients showed that LLV group had higher HBV DNA load, qHBsAg level, qHBeAg level, HBeAg positive rate, and the proportion of genotype C HBV infection but decreased HBV DNA during treatment (P < 0.001) at baseline; (3) the biochemical characteristics of patients showed that LLV group had lower serum ALT levels (P = 0.007) at baseline; (4) the noninvasive fibrosis markers of patients showed that LLV group were characterized by high aspartate aminotransferase platelet ratio index (APRI) (P = 0.02) and FIB-4 (P = 0.027) at baseline. HBV DNA, qHBsAg and qHBeAg were positively correlated with LLV occurrence (r = 0.559, 0.344, 0.435, respectively), while age and HBV DNA reduction were negatively correlated (r = -0.098, -0.876, respectively). Logistic regression analysis showed that ETV treatment history, high HBV DNA load at baseline, high qHBsAg level, high qHBeAg level, HBeAg positive, low ALT and HBV DNA level were independent risk factors for patients with CHB who developed LLV with NAs treatment. Multivariate prediction model had a good predictive value for LLV occurrence [AUC 0.922 (95%CI: 0.897 ~ 0.946)]. Conclusion: In this study, 37.1% of CHB patients treated with first-line NAs has LLV. The formation of LLV is influenced by various factors. HBeAg positivity, genotype C HBV infection, high baseline HBV DNA load, high qHBsAg level, high qHBeAg level, high APRI or FIB-4 value, low baseline ALT level, reduced HBV DNA during treatment, concomitant family history, metabolic liver disease history, and age < 40 years old are potential risk factors for developing LLV in patients with CHB during the therapeutic process.

Chemical Constituents， Pharmacology， and Toxicology of Asari Radix et Rhizoma： A Review / 中国实验方剂学杂志

Asari Radix et Rhizoma （AR） is a traditional Chinese medicine with a history of more than 2 000 years of medication and has been included in ancient herbal works in the past dynasties. It is effective in releasing the exterior， dispersing cold， dispelling wind， relieving pain， opening orifices， warming the lung， and resolving fluids， and is still widely used in the clinical treatment of influenza， coronavirus disease-2019 （COVID-19） pneumonia， asthma， allergic rhinitis， eye pain， headache， toothache， oral ulcer， eczema， etc. Modern pharmacological studies have shown that AR has antipyretic， anti-inflammatory， analgesic， antibacterial， antiviral， relieving cough and asthma， anti-allergy， and other effects. AR contains a variety of chemical components， in which essential oil is not only associated with functions such as dispelling cold， relieving heat， relieving pain， and resisting inflammation and allergy， but is also toxic. AR also contains lignans， flavonoids， amides， phenanthrenes， alkaloids， and other non-volatile oil components， which play an important role in immunity regulation， anti-inflammation， pain relief， heart strengthening， and blood vessel expansion. The phenanthrene compounds are mainly aristolochic acid analogues， such as aristolochic acid Ⅳa and aristolochic lactam Ⅰ. Aristolochic acid Ⅳa has been proven to have a significant anti-inflammatory effect. The toxicity of AR is related to safrole， aristolochic acids and their analogues， and is also affected by many factors， such as preparation method， dosage， origin， collection time， medicinal part， and decocting time， which should be comprehensively considered in clinical application. Based on the relevant literature in China and abroad， the present study reviewed the correlation of chemical composition and pharmacological and toxicological effects of AR， and the safety of AR， aristolochic acid， safrole， and other components to provide a new perspective for an objective understanding of AR safety， as well as references for rational clinical application， production risk prevention and control， and drug scientific supervision of AR.

Algunas características del tratamiento con insulina en el paciente con diabetes mellitus tipo 2

Introducción: La insulina es un importante fármaco que puede ser empleado en el tratamiento del paciente diabetes mellitus tipo 2. Objetivo: Describir algunas de las características del tratamiento con insulina en el paciente con diabetes mellitus tipo 2. Métodos: La información necesaria para redactar el presente artículo se obtuvo en el trimestre octubre-diciembre de 2020. Se utilizó como motores de búsqueda de información científica a Google Académico, Pubmed y Scielo. Se evaluaron diferentes trabajos de revisión, de investigación y páginas web, que en general tenían menos de 10 años de publicados, en idioma español, portugués o inglés. Fueron utilizadas como palabras clave: tratamiento; insulina; análogos de insulina; diabetes mellitus. Fueron excluidos los artículos que no reunían las condiciones señaladas. Esto permitió el estudio de 80 artículos, de los cuales 43 fueron referenciados. Conclusiones: La insulina es una hormona polipeptídica sintetizada por las células β de los islotes de Langerhans del páncreas. Su efecto es ejercido fundamentalmente a nivel del hígado, tejido adiposo y músculo, y es una opción terapéutica en cualquier fase evolutiva de la diabetes mellitus tipo 2, cuando los agentes orales no logran las metas o si se presentan ciertas complicaciones. Se dispone de una amplia gama de tipos de insulina con distintos perfiles de acción y concentración, lo que permite clasificarlas de diferentes maneras. Se han establecido diferentes criterios sobre cuándo se debe comenzar y cómo orientar el tratamiento con insulina en la persona con diabetes mellitus tipo 2, lo que hacen posible un mejor control glucémico.

Introduction: Insulin is an important drug that can be used for providing treatment to the patient with type 2 diabetes mellitus. Objective: To describe some of the characteristics of insulin treatment in patients with type 2 diabetes mellitus. Methods: The necessary information for writing this article was obtained in the trimester October-December 2020. As search engines for scientific information, Google Scholar, Pubmed and SciELO were used. Different review papers, research papers and web pages were assessed, generally less than ten years old and published in Spanish, Portuguese or English. The following keywords were used: tratamiento [treatment], insulina [insulin]; análogos de insulina [insulin analogues], diabetes mellitus. The articles not meet the above conditions were excluded. This allowed the study of eighty articles, of which 43 were referenced. Conclusions: Insulin is a polypeptide hormone synthesized by the β cells of the islets of Langerhans of the pancreas. Its effect is produced primarily at the liver, adipose tissue and muscle levels. It is a therapeutic option in any evolutionary phase of type 2 diabetes mellitus, when oral agents fail to achieve goals or if certain complications occur. A wide range of insulin types with different action and concentration profiles are available, allowing them to be classified in different ways. Different criteria have been established about when to start and how to guide insulin treatment in the person with type 2 diabetes mellitus, making better glycemic control possible.

Leiomioma parasitario retroperitoneal: reporte de un caso / Retroperitoneal parasitic leiomioma: A case report

Resumen ANTECEDENTES: Los leiomiomas parasitarios son una variante poco común de la miomatosis uterina. Se han identificado en la pared abdominal, intestino delgado, muñón cervical o vaginal, vasos iliacos, ovarios, colon sigmoides y en el omento mayor. OBJETIVO: Reportar un caso clínico de leiomioma parasitario retroperitoneal y revisar la bibliografía al respecto. CASO CLÍNICO: Paciente de 57 años, con diagnóstico de NIC-III y hemorragia uterina anormal. Acudió a consulta debido a una sensación de masa y dolor abdominal, pérdida de peso subjetiva, hiporexia, disfagia y plenitud gástrica de cuatro meses de evolución. En los estudios de extensión se documentó una masa retroperitoneal grande y elevación de los marcadores tumorales Ca 125 y Ca 19-9. La resección de la masa se efectuó mediante laparotomía, con hallazgo histopatológico de mioma parasitario. CONCLUSIÓN: Los leiomiomas parasitarios deben considerarse en el diagnóstico diferencial de pacientes con antecedente de histerectomía o miomectomía, sobre todo en el contexto de la morcelación. El tratamiento consiste en cirugía o inhibidores de la aromatasa y análogos de la hormona liberadora de gonadotropina (leiomiomatosis peritoneal diseminada).

Abstract BACKGORUND: Parasitic leiomyomas are a rare entity, defined as an unusual variant of uterine myomatosis. Have been documented in the abdominal wall, small intestine, cervical or vaginal stump, iliac vessels, ovaries, sigmoid colon, and greater omentum. OBJECTIVE: To report a clinical case of retroperitoneal parasitic leiomyoma and review the literature. CLINICAL CASE: A 57-year-old patient with a diagnosis of CIN-III and secondary abnormal uterine bleeding, who consulted for a sensation of abdominal mass and pain, subjective weight loss, hyporexia, dysphagia and gastric fullness, of four months of evolution. Extension studies document a large retroperitoneal mass and elevation of tumor markers Ca 125 and Ca 19-9. We practice surgical management of her gynecological pathology and resection of the mass by laparotomy, with histopathological finding of myoma. CONCLUSION: Parasitic leiomyomas should be suspected in patients with a detected mass and a history of hysterectomy or myomectomy, especially in the context of morcellation. The treatment of this condition is surgical and, in cases of disseminated peritoneal leiomyomatosis, pharmacological treatments have been used with aromatase inhibitors and gonadotropin-release hormone analogues.

Discontinuation of nucleoside/nucleoside analogues therapy in compensated patients with hepatitis B cirrhosis after HBsAg negative conversion / 中华临床感染病杂志

Objective:To evaluate the safety of discontinuing nucleoside/nucleoside analogue (NAs) therapy in patients with compensated hepatitis B cirrhosis after HBsAg negative conversion.Methods:A total of 3 783 patients with hepatitis B cirrhosis in compensated stage were treated with NAs at Taizhou Hospital, Taizhou Municipal Hospital and Taizhou Enze Hospital from January 2008 to December 2020. The clinical data and laboratory tests results of 85 patients with HBsAg negative conversion were retrospectively analyzed, including 36 cases discontinued the drug, and 49 continued to use drug. Chi-square test and rank-sum test were used for data analysis.Results:During the 24 and 48 months of follow-up, the ALT levels were within the normal range in both groups. There were no significant differences in positive rates of anti-HBs and HBeAg ( χ2=0.75, 0.39 and 0.90, P=0.78 0.84 and 0.34; χ2=0.40, 0.00 and 0.00, P=0.84, 1.00 and 1.00) between two groups. After 48 months of follow-up, 2 cases of primary liver cancer occurred in the discontinuation group and no primary liver cancer occurred in the continuation group ( χ2=0.89, P=0.34). Throughout the follow-up, HBsAg remained negative and HBV DNA load was below the lower limit of detection in both groups. Conclusions:Discontinuation of NAs can be considered after the HBsAg negative conversion in patients with compensated hepatitis B cirrhosis.

Non-alcoholic fatty liver disease: Epidemiology, pathophysiology and an update on the therapeutic approaches

Non-alcoholic fatty liver disease (NAFLD) denotes a spectrum of fatty liver disease in individuals without significant alcohol consumption. NAFLD is set to be the most common etiology of serious liver diseases in numerous nations when accompanied by obesity and type 2 diabetes. It is further histologically categorized into the non-alcoholic fatty liver (NAFL; steatosis without hepatocellular injury) and non-alcoholic steatohepatitis (NASH) which is characterized by the coexistence of hepatic steatosis and inflammation and is accompanied by hepatocyte injury (ballooning), either with or without fibrosis. NAFL is considered the benign and reversible stage arising from the excessive accumulation of triglycerides in hepatocytes. However, NASH is a more progressive stage of NAFLD, due to the increased risks of evolving more serious diseases such as cirrhosis, hepatocellular carcinoma. This concept, however, has been lately challenged by a hypothesis of multiple parallel hits of NAFLD, in which steatosis and NASH are separate entities rather than two points of the NAFLD spectrum, not only from a set of histological patterns but also from a pathophysiological perspective. The current review highlights the epidemiology and pathophysiology of NAFLD, and its progression towards steatohepatitis, with special focus on the novel imminent therapeutic approaches targeting the molecular aspects and the pathogenic pathways involved in the development, and progression of NAFLD.

Hypoglycemia frequency and treatment satisfaction in patients receiving insulin analogues for treatment of type 1 diabetes mellitus

ABSTRACT Objective: The aim of this study was to evaluate the frequency of hypoglycemia and the treatment satisfaction in patients with type 1 diabetes (T1D) using insulin analogues. Subjects and methods: This observational retrospective study included 516 adult patients with T1D from 38 cities in Southern Brazil. Demographics and clinical data were collected using a self-report questionnaire. Hypoglycemia was defined as an event based on either symptoms or self-monitored blood glucose < 70 mg/dL. Treatment satisfaction was evaluated using the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) and with a specific question with scores ranging from 0-10. Common mental disorders were assessed using the General Health Questionnaire (GHQ-12). Results: Overall, the mean age was 38 ± 14 years and 52% of the participants were women. The median diabetes duration was 18 years. The scores for insulin analogue treatment satisfaction were higher than those for previous treatments. DTSQ scores had a median value of 32 (interquartile range 29-35) and remained unchanged over time. The percentage of patients with hypoglycemia (including severe and nocturnal) was comparable across groups divided according to duration of use of insulin analogues. Most patients (n=395, 77%) screened positive for common mental disorders. Conclusions: Patient satisfaction with insulin analogue treatment was high and remained unchanged with time. Episodes of hypoglycemia also remained unchanged over time among patients using insulin analogues.

Current status of the treatment of chronic hepatitis B / 临床肝胆病杂志

Chronic hepatitis B caused by hepatitis B virus (HBV) infection is a global public health issue. Antiviral therapy for chronic HBV infection plays a critical role, and the goal of antiviral therapy is mainly defined by virological, serological, and biochemical parameters. As the two types of antiviral drugs approved for marketing, both interferon and nucleos(t)ide analogues can alleviate liver inflammation and liver fibrosis and reduce the incidence rates of liver cirrhosis and hepatocellular carcinoma. However, the ideal goal of antiviral therapy is functional cure, which significantly improves the long-term outcome of chronic hepatitis B. The limitation of current treatment is that it can inhibit HBV replication, but cannot clear the virus, with low serological clearance rates of HBeAg and HBsAg. Development of new drugs with the goal of functional cure and evaluation of the synergistic and combined effects of existing drugs are important directions for HBV treatment and development.

Effect of long-term topical administration of prostaglandins on bulbar conjunctival thickness in rabbits / 中华实验眼科杂志

Objective:To investigate the effect of long-term application of prostaglandin analog drops on bulbar conjunctival thickness in rabbits.Methods:Twenty-four healthy New Zealand white rabbits were randomly divided into latanoprost group, carteolol group and blank control group using the random number table method, with 8 rabbits in each group.The left eyes of rabbits were taken as experimental eyes.The rabbits in the latanoprost group and carteolol group were given latanoprost eye drops or carteolol eye drops once a day for 2 months according to grouping.The bulbar conjunctival thickness of left eyes of the latanoprost group and carteolol group were measured by optical coherence tomography (OCT) at baseline and two months after administration, respectively.The conjunctival tissue of the three groups were extracted to investigate the protein and mRNA expression level of matrix metalloproteinases-1 (MMP-1) and MMP-3 by Western blot and real-time fluorescence quantitative polymerase chain reaction (PCR). The study protocol was approved by an Ethics Committee of Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (No.2017-0014). The use and care of the experimental animals complied with the ARVO Statement.Results:In the latanoprost group, the conjunctival thickness was significantly reduced from baseline (178.88±5.23)μm to (124.19±11.29)μm at 2 months after administration ( P<0.01). In the carteolol group, there existed no significant difference in the conjunctival thickness between baseline (184.94±11.85)μm and (183.31±8.71)μm at 2 months after administration ( P>0.05). The conjunctival thickness at 2 months after administration of the latanoprost group was significantly thinner than that of the carteolol group ( P<0.01). The protein and mRNA expression levels of MMP-1 and MMP-3 in conjunctival tissue of the latanoprost group were significantly higher than those of the blank control group and carteolol group (all at P<0.01). Conclusions:The long-term topical use of prostaglandin analog drops can significantly reduce the bulbar conjunctival thickness in rabbits.The mechanism may be related to the elevated expression levels of MMP-1 and MMP-3 in the bulbar conjunctival tissue.

Role of the stability of deoxyribonucleoside triphosphate pool in the development and progression of tumors / 肿瘤研究与临床

The stability of deoxyribonucleoside triphosphate (dNTP) pool is essential for the normal synthesis of nuclear and mitochondrial DNA. The lack or excess of any dNTP may cause DNA damage and genomic instability, and increase mutation rate. Present studies have confirmed that the instability of dNTP pool is closely related to a variety of tumorigenesis. In addition, dNTP pool is involved in the development of tumor via multiple pathways, while the mechanisms of tumors caused by the instability of dNTP are complicated. This paper discusses the relationship between the stability of dNTP pool and DNA damage repair to provide a theoretical basis for early diagnosis and targeted treatment of tumors.

El efecto de los antihiperglicemiantes en los parámetros ecocardiográficos diastólicos y sistólicos / The effect of antihyperglycemic agents on diastolic and systolic echocardiographic parameters

Resumen La enfermedad metabólica diabetes mellitus tipo 2 ocasiona alteraciones en la estructura y en la funcionalidad miocárdica por diferentes mecanismos bioquímicos los cuales pueden ocasionar disfunción diastólica y sistólica, por lo cual el uso de los antihiperglicemiantes aparte de su efecto en la reducción de la hiperglicemia y la hemoglobina glicosilada, algunos han demostrado reducción en la mortalidad cardiovascular y de las hospitalizaciones por insuficiencia cardiaca, basado en estudios clínicos sobre este impacto en el miocardio. También se ha evaluado el efecto de estos fármacos por medio del ecocardiograma transtorácico. El objetivo de este articulo es analizar los valores de los parámetros ecocardiográficos sistólicos y diastólicos en pacientes diabéticos tipo 2 o alguna cardiopatía de base como antecedente de infarto al miocardio e insuficiencia cardiaca con el uso de metformina, sulfonilureas, los inhibidores de la dipeptidilpeptidasa 4 (sitagliptina, alogliptina y linagliptina, vildagliptina), los análogos de GLP1 (liraglutide, albiglutide y exenatide).

Abstract Metabolic disease type 2 diabetes mellitus causes alterations in both structure and myocardial functionality by different biochemical mechanisms which can cause diastolic and systolic dysfunction, which is why the use of antihyperglycemic agents apart from its effect in the reduction of hyperglycemia and glycosylated hemoglobin, some groups have shown reduction in cardiovascular mortality and hospitalizations for heart failure this based on clinical studies, by hypothesis, theories and pleiotropic mechanisms on this impact on the myocardium. On the other hand, the effect of these drugs on the myocardium has also been evaluated by transthoracic echocardiography. Therefore, the aim of this article is to analyze the values of systolic and diastolic echocardiographic parameters in type 2 diabetic patients or some underlying heart disease as a history of myocardial infarction and heart failure with the use of metformin, sulfonylureas, inhibitors of the dipeptidylpeptidase 4 (sitagliptin, alogliptin and linagliptin, vildagliptin), GLP1 analogues (liraglutide, albiglutide and exenatide).

Diagnostic value of urinary luteinizing hormone levels in the monitoring of precocious puberty treatment

ABSTRACT Objective To determine whether first-voided urinary LH (FV-ULH) - level measurement can adequately assess pubertal suppression as much as standard tests can. Subjects and methods The study group included patients with central precocious puberty and rapidly progressing early puberty who received up to 3 - 4 doses of GnRHa therapy monthly and did not have adequate hormonal suppression after GnRH stimulation (90-minute LH level > 4 IU/L). Design: All of the participants underwent an LHRH test just after admission to the study. According to the stimulated peak LH levels, the patients were divided into 2 groups and followed until the end of the first year of treatment. The concordance between FV-ULH and stimulated LH levels was assessed. Results The FV-ULH levels in patients with inadequate hormonal suppression were significantly high compared to patients with adequate hormonal suppression. FV-ULH levels were very strongly correlated with stimulated LH levels (r = 0.91). Its correlation with basal LH levels was significant (r = 0.65). However, this positive correlation was modestly weakened after the first year of treatment. The cutoff value for FV-ULH of 1.01 mIU/mL had the highest sensitivity (92.3%) and specificity (100%). Conclusion FV-ULH levels, using more reliable and sensitive assay methods, can be used to monitor the adequacy of GnRHa therapy.

Studies On Bioavailability Enhancement Of Curcumin

Objective: The objective of the present work was to improve aqueous solubility and in vivo bioavailability of curcumin and structural analogues of curcumin such as potassium, calcium, magnesium salts and nitro derivative. Methods: Structural analogues of curcumin were prepared by reaction of curcumin with potassium chloride, magnesium chloride hexahydrate and calcium chloride dihydrate in a suitable solvent. The nitro derivative synthesized by treating curcumin with sulphuric acid and nitric acid. The prepared analogues were evaluated for melting behavior, solubility, UV spectrophotometry, partition coefficient, moisture content, cellular uptake, FTIR analysis, antimicrobial activity and in vivo bioavailability in the rat. Results: Chemical modification of curcumin increased the saturation solubility to 11.6, 16.5, 21.5, 28.0 µg/ml in calcium salt, magnesium salt, potassium salt and nitro derivative respectively, against 8.6 µg/ml of curcumin. The analogues were chemically stable as curcumin analyzed by FTIR spectrophotometry. Increased cellular uptake, as well as enhanced antimicrobial activity, was demonstrated by modified curcumin analogues. Moreover, significant improvement in plasma levels was estimated with nitro derivative. Conclusion: The present work recommends that nitration of curcumin improves aqueous solubility which may improve absorption and in vivo bioavailability.

Cost-effectiveness Analysis of Insulin Analogues and Human Insulin in the Treatment of Type 2 Diabetes Mellitus Based on Net-benefit Regression Framework / 中国药房

OBJECTIVE：To compare the cost-effectiveness of insulin analogues and human insulin in the treatment of type 2 diabetes mellitus ，to reduce economic burden of patients ，and to provide new ideas for non-randomized pharmacoeconomic research. METHODS ：Retrospective data of a Third-grade Class-A hospital were adopted and 533 patients with type 2 diabetes were taken as object to balance the difference between groups through propensity score matching ，and construct net-benefit regression framework so as to analyze the cost-effectiveness of insulin analogues and human insulin in the treatment of type 2 diabetes mellitus. RESULTS ：There was a positive relationship between the efficacy and cost of the two therapeutic schemes ，i.e. insulin analogues were more effective than human insulin ，and the difference of total effective rate between the two schemes was 14.5％. The corresponding treatment cost of insulin analogues was higher than that of human insulin ，and the average total cost difference was 960.3 yuan. The cost of insulin analogues was 66.23 yuan more than that of human insulin for each additional unit of clinical effect （total effective rate ）. Results of net-benefit regression analysis showed that critical value of willingness to pay of therapy plan was 16 947.5 yuan. CONCLUSIONS ：When the willingness to pay is more than 16 947.5 yuan，the insulin analogue scheme is suitable ；on the contrary ，the human insulin analogue scheme is suitable. The propensity scoring technology used for the net-benefit regression analysis can broaden the source of avaliable data for non-randomized pharmacoeconomic evaluation.

Identification of Bupleurum marginatum var. Wall. ex DC stenophyllum (Wolff) Shan et Li and its analogues based on ITS2 barcode / 中草药

Objective: DNA barcoding technology, a molecular identification method, is applied to distinguish Bupleurum marginatum var. stenophyllum from its analogues in order to ensure the quality and clinical curative effect. Methods: In this study, the internal transcribed spacer 2 (ITS2) regions of 50 samples were amplified by PCR and sequenced bi-directionally. Obtained sequences were assembled using CodonCode Aligner. The genetic distances were computed by MEGA 6.0 in accordance with the kimura 2-parameter (K2P) model and the phylogenetic tree was constructed by Neighbor-joining (NJ) method. Moreover, the secondary structure of ITS2 was predicted using ITS2 database websites. Results: The intra-specific genetic distances were smaller than inter-specific ones in ITS2 regions of B. marginatum var. stenophyllum. The NJ tree and secondary structure results could distinctly differentiate B. marginatum var. stenophyllum and its analogues. Conclusion: ITS2 sequence can scientifically and reliably identify the authenticity of B. marginatum var. stenophyllum and could provide more new and reliable techniques to ensure clinical safety of this traditional Chinese medicine.

The Synthesis, Screening Of Novel 1-Substituted-3-(4-Oxo-2-Phenylquinazolin-3(4h)-Yl) Urea And Thiourea Analogues As Potent Antibacterials

Objective: The proposed study is an attempt to determine antibacterial activity of synthesized novel 1-substituted-3-(4-oxo-2-phenylquinazolin-3(4H)-yl) urea and thiourea analogues as potent antibacterials against S. aureus and E. coli bacteria. Methods: The present study reports new series of 1-substituted-3-(4-oxo-2-phenylquinazolin-3(4H)-yl) urea and thiourea derivatives as potent antibacterial agents. Reagents used in the present study were of synthetic grade and solvents were used after distillation. Novel quinazolinone analogues were synthesized by considering substitution pattern, characterization of the synthesized analogues was performed using various techniques like Thin layer chromatography, Melting point, Infrared spectroscopy, Proton NMR spectrometry and Mass spectrometry. TLC of the synthesized analogues was carried out by using (toluene: methanol in the ratio 2:1), melting point was found by open capillary method, IR spectrum was recorded on JASCO V-530, 1H NMR was recorded on Bruker Avance Spectrometer and Mass spectra were obtained from G6460A, triple quadrupole/MS/MS system. In vitro antibacterial activity was performed against S. aureus and E. coli. Results: Six derivatives of quinazolinone analogues were synthesized. The structures of 1-substituted-3-(4-oxo-2-phenylquinazolin-3(4H)-yl) urea and thiourea derivatives were confirmed by physical and spectral analysis. Synthesized molecules showed Rf of 0.45-0.80 in toluene: methanol mobile phase, melting point was carried out by open capillary method and were in range of 90-210 ° C, IR spectrum was recorded in range of 14000-400 cm-1and showed characteristic peaks of NH and of C-O-NH, 1H NMR of the compounds was distinct to confirm structures with delta values in the range of 7.53-11.960, Mass spectra proved parent peaks of synthesized compounds confirming molecular weight. The compounds were assayed for antibacterial activity against S. aureus and E. coli using ciprofloxacin as standard. The synthesized analogues have shown good yield and comparable antibacterial. Conclusion: The present study delivers a convenient and efficient protocol for the quinazolinone analogues synthesis.