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Objective: To evaluate the safety of umeclidinium/vilanterol in Chinese participants in a real-world setting. Methods: This was a 24-week, prospective, multicenter, single-arm, observational study that enrolled participants treated with umeclidinium/vilanterol in real-world settings from 14 sites in China from 14 December 2020 to 30 January 2022. The primary outcomes were the incidence of adverse events (AEs) and serious adverse events (SAEs) at week 24. Results: A total of 887 participants on umeclidinium/vilanterol were enrolled. The mean (±SD) age of these participants was 67.5 (±9.6) years, with more men (77.7%) enrolled. The majority of the participants (98.1%) had been diagnosed with chronic obstructive pulmonary disease, and 67.6% of them reported comorbidities. More than half of the participants (52.8%) were taking concomitant medication in addition to the study treatment. AEs were reported in 59 (6.7%) participants and were predominantly mild to moderate in severity. SAEs were reported in 21 (2.4%) participants, including 9 fatal SAEs, 10 reported non-fatal SAEs, and 2 reported both non-fatal and fatal SAEs. None of the SAEs, including the fatal events, were considered by the investigators to be related to umeclidinium/vilanterol. Adverse drug reactions (ADRs) were reported in 6 (0.7%) participants with 4 preferred terms (PTs), all of which were considered mild in severity. Of these PTs, 2 were known ADRs of umeclidinium/vilanterol. Three participants (0.3%) reported AEs that were part of serious identified/potential hazards, all of which were considered by the investigators to be unrelated to umeclidinium/vilanterol. Conclusion: The results of this study showed that umeclidinium/vilanterol was well tolerated in Chinese participants in a real-world setting and no new drug-related safety signals were observed.
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Alcoholes Bencílicos , Clorobencenos , Quinuclidinas , Humanos , Alcoholes Bencílicos/administración & dosificación , Alcoholes Bencílicos/efectos adversos , Estudios Prospectivos , Clorobencenos/efectos adversos , Clorobencenos/administración & dosificación , Quinuclidinas/efectos adversos , Quinuclidinas/administración & dosificación , Anciano , Masculino , Femenino , China , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Persona de Mediana Edad , Pueblo Asiatico , Pueblos del Este de AsiaRESUMEN
Objective: To evaluate the effects of re-tucking the superior oblique muscle on recurrent or residual compensatory head position. Methods: A retrospective case series study was conducted. 12 recurrent or residual compensatory head position patients (12 eyes) with congenital superior oblique palsy who underwent superior oblique re-tucking in Tianjin Eye Hospital from March 2015 to February 2021 were included. All patients had a history of superior oblique tucking procedure and showed signs of superior oblique muscle palsy without inferior oblique muscle overaction. During surgery, the Guyton forced duction test is used to evaluate the relaxation of the superior oblique muscle tendon, which affects the re-tucking length of the muscle.Their head position, vertical deviation, eye movement, fovea-disa angle, and Bielschowsky head tilt test were assessed pre-and post-surgery. Statistical analysis was performed using ttest and paired samples Wilcoxon signed rank test. Results: Out of the 12 patients, 8 were male and 4 were female, aged between 2 and 9 years. The initial surgery was done at age 6, with a superior oblique recession length of (7.17±1.03) mm. Recurrent head tilt occurred in 11 patients after (3.82±0.98) months postoperatively, and 1 patient had residual head tilt, with a followup period of six months or more. Ocular motility examination revealed underaction of the superior oblique muscle, positive Bielschowsky's head tilt test, and Guyton forced duction tese indicating relaxation of the paralyzed superior oblique muscle tendon. Scar adhesion was observed at the stop of the superior oblique muscle, as well as the previous sutures. The scar and the sutures around the stop of the superior oblique muscle were released, the mean re-tucking amount was(7.83±1.59)mm. Follow-up at 12 to 18 months postoperatively showed disappearance of compensatory head position, significant improvement in superior oblique muscle lag, normal ocular motility, and no occurrence of Brown syndrome. The results of Bielschowsky head tilt were negative in 9 cases and still positive in 3 cases after superior oblique re-tucking. The primary vertical deviation was 2.5 (2.0, 5.3) prism diopter pre-operatively and 1 (0, 1) prism diopter post-operatively, respectively. The difference was statistically significant (U=6.00, P<0.001). The total amount of FDA in both eyes was (-22.04±5.47)° and (-15.27±6.08)° pre-and post-operatively, respectively. The difference was statistically significant (t=2.87, P=0.009). All 12 patients have normal eye movement after superior oblique re-tucking procedure. All patients had no compensatory head position at last follow-up. Conclusions: Superior oblique re-tucking is suitable for patients with relaxation of the superior oblique muscle tendon and extrocular rotation as the main sign. It can effectively and safely correct the recurrent or residual compensatory head position after re-tucking the superior oblique muscle.
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Trastornos de la Motilidad Ocular , Oftalmoplejía , Estrabismo , Humanos , Masculino , Femenino , Preescolar , Niño , Músculos Oculomotores/cirugía , Estudios Retrospectivos , Cicatriz/cirugía , Estrabismo/cirugía , Procedimientos Quirúrgicos Oftalmológicos , Trastornos de la Motilidad Ocular/cirugía , Resultado del TratamientoRESUMEN
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a major public health concern. Nucleocapsid (N) protein is the most abundant structural protein on SARS-CoV-2 virions and induces the production of antibodies at the early stage of infection. Large-scale preparation of N protein is essential for the development of immunoassays to detect antibodies to SARS-CoV-2 and the control of virus transmission. In this study, expression of water-soluble N protein was achieved through inducing protein expression at 25°C with 0.5 mM IPTG for 12 h. Western blot and ELISA showed that recombinant N protein could be recognized by sera collected from subjects immunized with Sinovac inactivated SARS-CoV-2 vaccine. Four monoclonal antibodies namely 2B1B1, 4D3A3, 5G1F8, and 7C6F5 were produced using hybridoma technology. Titers of all four monoclonal antibodies in ELISA reached more than 1.28×10 6.0. Moreover, all monoclonal antibodies could react specifically with N protein expressed by transfection of pcDNA3.1-N into BHK-21 cells in IPMA and IFA. These results indicated that water-soluble N protein retained high immunogenicity and possessed the same epitopes as that of native N protein on virions. In addition, the preparation of water-soluble N protein and its monoclonal antibodies laid the basis for the development of immunoassays for COVID-19 detection.
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COVID-19 , Proteínas de la Nucleocápside , Animales , SARS-CoV-2 , Vacunas contra la COVID-19 , COVID-19/veterinaria , Anticuerpos Monoclonales , Proteínas Recombinantes , Anticuerpos AntiviralesRESUMEN
Objective: To evaluate the perfusion features of the anterior segment in patients with different types of strabismus. Methods: A cross-sectional study. Sixteen strabismus patients (16 eyes) who received the examination of iris indocyanine green angiography (ICGA) in Tianjin Eye Hospital from November 2016 to December 2021 were enrolled and divided into two groups according to whether they had a history of extraocular muscle injury/rectus muscle surgery. All patients underwent routine ophthalmic examinations. Angiographic images were obtained by the anterior segment camera, and indicators such as arm to iris circulation time, whole iris filling time, regression onset time, and complete regression time were recorded. The independent sample t test or Mann-Whitney U test was used to compare iris perfusion aspects of the two groups, and the Pearson/Spearman correlation tests was used to analyze the correlation of arm to iris circulation time and whole iris filling time with age and course of strabismus. Results: Among the 16 patients, there were 10 males and 6 females. The mean age was (49.2±13.2) years, and the course of strabismus ranged from 2 to 31 months. There were 7 patients in the group of without extraocualr muscle injury and 9 patients in the extraocular muscle injury/surgery group. There was no significant difference in age and course of strabismus between the two groups (both P>0.05). The arm to iris circulation time [M (Q1, Q3)] of the group without extraocular muscle injury and the group with extraocular muscle injury/surgery were 18 (18, 21) and 22 (20, 24) s, respectively. The average whole iris filling time was (13.86±1.95) and (12.22±3.60) s, respectively. There was no statistical significance between the two groups (both P>0.05). Correlation analysis showed that arm to iris circulation time was not correlated with age and course of strabismus (r=-0.033, -0.079; both P>0.05). And the whole iris filling time was not correlated with age and course of disease (r=0.057, -0.119; both P>0.05). The matrix scatter plots showed that in the group of extraocular muscle injury/surgery, there were three patients who were older than the average (49.2 years) and above the median of arm to iris circulation time (20 s) (two cases with the vertical muscle involved), meanwhile, there were three patients (all with the vertical muscle involved) whose course of strabismus was longer than 6 months and above the median of arm to iris circulation time, which were more than those in the group of without extraocular muscle injury (1 case, respectively). Conclusions: ICGA in patients with strabismus show that a history of injury to the extraocular muscle or surgical treatment beyond 2 months had no effect on iris perfusion. Age and course have no correlation with iris reperfusion. The vertical muscle involvement has more effects on the blood supply to the anterior segment.
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Verde de Indocianina , Estrabismo , Segmento Anterior del Ojo , Preescolar , Estudios Transversales , Femenino , Angiografía con Fluoresceína/métodos , Humanos , Lactante , Iris/diagnóstico por imagen , Isquemia , Masculino , Estrabismo/cirugíaRESUMEN
Objective: To observe the effectiveness of the graded vertical rectus tenotomy procedure for small-angle vertical deviation. Methods: Retrospective case series study. Twelve patients, including 8 males and 4 females, with an average age of (48±8) years were treated in Tianjin Eye Hospital from January 2017 to December 2019 for diplopia in primary gaze by strabismus surgery. The disease duration was (15±7) months. MRI/CT scan of the orbits and brain was performed to exclude the orbital and craniocerebral diseases. All patients underwent ocular movement examination, with the prism and alternate cover test to detect the deviation angle in primary gaze and the double Maddox test. Based on the results, the posterior segment of the nasal/temporal superior/inferior rectus muscle was operated. The changes of vertical and cyclotorsion deviation angle and the relationship between the vertical rectus graded tenotomy and corrected vertical deviation angle were observed at 1 day after surgery and the last follow-up. The vertical deviation angle was represented by M (Q1, Q3). Friedman test (Bonferroni correction) and linear fitting analysis were used for statistical analysis. Results: The follow-up time of all patients was (7±3) months. The vertical deviation angle in primary gaze before surgery [7.00 (5.25, 7.75) PD] was significantly different from that at 1 day after surgery [1.00 (1.00, 2.00) PD] and the last follow-up [1.50 (1.00, 2.00) PD] (P<0.001, P=0.003). There was no significant difference in postoperative cyclotorsion in all patients. Linear fitting results showed that 50% to 90% vertical rectus tenotomy corrected 5 to 8 PD vertical deviation (R2=0.72; P<0.001). Conclusion: The graded vertical rectus tenotomy procedure can effectively improve the small-angle vertical deviation in primary gaze.
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Estrabismo , Tenotomía , Adulto , Diplopía/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculos Oculomotores/cirugía , Estudios Retrospectivos , Estrabismo/cirugía , Tenotomía/métodosRESUMEN
The toxicity data of chemicals and drugs increases rapidly, while the animal experimental-based tests method could not meet the current demand of health risk assessment. The high-throughput screening techniques based on in vitro alternative models, integrating with computational methods and information technology to establish toxicity tests strategy promises to address this problem. High-content screening (HCS) technology uses automated microscopy and quantitative image platforms to perform multi-parameter and high-throughput phenotypic analysis via a visualization and quantification manner, and to quickly and effectively assess toxicity and prioritization of chemicals, which promotes the development of in vitro toxicity tests and computational toxicology. HCS technology has been included as an important tool for Toxicity Testing in the 21st Century (Tox21) and chemical risk prioritization. Its applications have been widely utilized in the research field of toxicity tests and chemical toxicity mechanisms. In this review, we describe the development of HCS technology, technical points, toxicological applications, and the future directions and challenges of HCS, so as to provide references for the toxicity testing technology and risk assessment methodology.
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Ensayos Analíticos de Alto Rendimiento , Pruebas de Toxicidad , Animales , Proyectos de Investigación , Medición de RiesgoRESUMEN
Objective: To investigate the clinical effect of anterior 1/3 superior oblique tendon tucking in acquired symptomatic excyclotropia adults. Methods: Retrospective case series. Seven patients (7 eyes) with acquired symptomatic excyclotropia who underwent an anterior 1/3 superior oblique tendon tuck procedure in Tianjin Eye Hospital from January 2019 to December 2019 were included. There were 5 male patients and 2 female patients, with an average age of (49±12) years old. All the patients had a history of a closed head injury. There was torsional diplopia in primary position, and eye movement examination showed paralysis of the superior oblique muscle in the affected eye, without obvious hyperactivity of the inferior oblique muscle. The anterior 1/3 tendon of the superior oblique muscle was tucked during surgery according to the relaxation of the superior oblique tendon in the forced duction test. The paired-sample nonparametric rank sum test was used to analyze the preoperative and postoperative (at 1 day after surgery and the last follow-up) excyclotropia angle. Results: The mean tuck amount was (7.7±1.8) mm (range, 6.0 to 10.0 mm). During operation, patients complained that excyclotropia improved markedly. The excyclotropia angle with the double Maddox rod test improved significantly from preoperative 10° (8°, 15°) to 2° (0°, 3°) at 1 day (Z=-2.379; P<0.05) and 2° (2°, 5°) at the last follow-up (Z=-2.375; P<0.05). The follow-up period was (112+38) days. All patients had no complaints of excyclotropia at the last follow-up. Conclusions: The anterior 1/3 superior oblique tendon tucking can effectively improve clinical symptoms in the primary position in adults with acquired excyclotropia and diplopia. The short-term postoperative results seem to be stable, without significant regression. (Chin J Ophthalmol, 2021, 57: 685-688).
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Músculos Oculomotores , Estrabismo , Adulto , Diplopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculos Oculomotores/cirugía , Estudios Retrospectivos , Estrabismo/cirugía , Tendones/cirugíaRESUMEN
Objective: To explore the clinical effects of partially de-epithelized local flaps in repairing tubercular chest wall defects. Methods: A retrospective observational study was conducted. From April 2010 to February 2021, twelve patients who met the inclusion criteria were admitted to the Department of Burns and Plastic Surgery of the Eighth Medical Center of PLA General Hospital, including 9 males and 3 females with age of (42±18) years. The sizes of tubercular chest wall defects of patients were ranged from 4 cm×3 cm×2 cm to 16 cm×8 cm×5 cm, which were all repaired with partial de-epithelized local flaps. The widths of flaps were equal to the widths of the defects, and the lengths of flaps were 2 cm longer than those of the defects. In one patient, the local flap was too large to close the donor site directly by suturing, so an autologous back free medium thickness skin graft was used for repair. In other patients, the collection areas of local flaps were small, and the donor areas of flaps were directly closed. The duration of operation, intraoperative bleeding, and postoperative drainage volume and indwelling time of drainage tube were observed and recorded. In two weeks after operation, the survival, color, and texture of flaps, the presence of subcutaneous hydrops and skin ulcer, and donor site healing including wound disruption, local infection, hematoma were observed. Chest X-ray, CT scan, or nuclear magnetic resonance imaging was performed in one month after operation to check whether new local hydrops and bone destruction occurred in the chest wall defects and the concomitant tuberculose focus of patients. All patients were followed up for more than 6 months to record whether the surgical incisions of the chest wall defects of the patients were complicated by hypertrophic scar, redness, swelling, and sinus. Results: In surgery, the patient had (104±18) min of operation duration, (119±53) mL of intraoperative bleeding, (134±49) mL of cumulative drainage of drainage tube, and (5.3±1.7) days of drainage tube indwelling time. In two weeks after operation, all the grafted local flaps survived, and the color and texture of flaps were similar to the surrounding normal skin. One patient had fluid leakage from the incision of chest wall defect area with the incision partially dehisced, which healed well after a phase â ¡ operation; no wound infection, subcutaneous hydrops, or wound rupture occurred in other patients. The incisions of donor sites in all the patients healed well and no wound disruption, local infection, or hematoma occurred. One month after operation, no new bone destruction was observed in the operative region by chest imaging examination. Patients were followed up for 6 to 96 months, with one patient having wound swelling, ulceration, and sinus in the operative area of the chest wall defect in 12 months after surgery, which healed after phase â ¡ operation; the incisions of chest wall defect wounds in other patients healed well and had no scar, redness and swelling, or sinus. Conclusions: Partially de-epithelized local flap could be used in repairing tubercular chest wall defect wounds, with the advantages of flexible flap design, minimal donor site injury, and good postoperative wound healing.
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Colgajo Perforante , Procedimientos de Cirugía Plástica , Traumatismos de los Tejidos Blandos , Pared Torácica , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trasplante de Piel , Traumatismos de los Tejidos Blandos/cirugía , Pared Torácica/cirugía , Resultado del Tratamiento , Adulto JovenRESUMEN
Objective: To understand the incidence of HIV infections and associated factors among men who have sex with men (MSM) in Jiangsu province. Methods: Based on national AIDS sentinel surveillance in 2019, MSM from 13 cities in Jiangsu were recruited for questionnaire interview and laboratory testing during April to July, 2019. Seropositive samples were tested with Limiting-antigen avidity enzyme immunoassay to detect recent HIV infections. The incidence of HIV infection in MSM were calculated according to the formula and parameters from China CDC. Multivariable logistic regression analysis was used to identify factors associated with recent infection of HIV. Results: A total of 4 469 MSM were subjects and the incidence of HIV infection were 4.5% (95%CI: 3.4%-5.5%).Multivariate logistic regression analysis results showed that compared with these aged ≥40 years, recruitment ways from MSM venues, awareness of AIDS knowledge, non-unprotected anal sex in the past 6 months and non-syphilis infection, those who aged 18-24 years (aOR=2.083,95%CI:1.087-3.990), recruitment ways from VCT clinics (aOR=2.125,95%CI:1.175-3.843), unawareness of AIDS knowledge (aOR=2.456,95%CI:1.109-5.437), unprotected anal sex in the past 6 months (aOR=3.553,95%CI:2.143-5.889) and syphilis infection (aOR=2.414,95%CI:1.033-5.462) were higher risk of HIV infection. Conclusion: The new infection rates of HIV were high in MSM in Jiangsu province. Health education, condom use and HIV/syphilis screening promotions should therefore be top priority in the prevention and control of HIV infection in MSM.
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Infecciones por VIH , Minorías Sexuales y de Género , Sífilis , China/epidemiología , Estudios Transversales , Infecciones por VIH/epidemiología , Homosexualidad Masculina , Humanos , Masculino , Prevalencia , Factores de Riesgo , Conducta Sexual , Encuestas y Cuestionarios , Sífilis/epidemiologíaRESUMEN
Objective: To screen the biomarkers in the exhaled breath of mice exposed to benzene by using exhaled breath online analysis system. Methods: Thirty 8-week-old male C57BL/6 mice were randomly divided into six groups (0, 3, 32, 324, 648, and 1 296 mg/m3) and treated with benzene vapour for 28 days. At the end of the exposure, the peripheral blood cell counts and blood glutathione (GSH) were detected. The content of malondialdehyde (MDA) in HL60 cells treated by mice plasma was examined. Exhaled breath data from mice were collected by Secondary electrospray ionization source high resolution mass spectrometry (SESI-HRMS). Targeted analysis underlying benzene metabolites and oxidative stress metabolites was performed to screen the biomarkers in exhaled breath. Results: After benzene exposure, the number of peripheral blood cells was decreased in different degrees, particularly in the white blood cells (WBC) number. The WBC in 32 and 324 mg/m3 groups was declined by 27.76% and 52.87%, respectively compared to that in control group (P<0.05). Meanwhile, compared with the control group, the GSH content of peripheral blood cells from 324 mg/m3 group decreased by 13.16% (P<0.05). In addition, MDA content was increased by 18.11% in HL60 cells treated with plasma from 324 mg/m3 group mice (P<0.05). The phenol, hydroquinone/catechol, benzenetriol and trans, trans-Muconic acid (t,t-MA) in the exhaled gas of mice could be used as biomarkers for benzene exposure (R2>0.8, P<0.001). The peak intensity of five small molecular metabolites related to oxidative stress (ω-carboxylic fatty acid C5H10O3, ω-carboxylic fatty acid C6H12O3, glutamate, cysteine and MDA) increased with the increase of benzene concentration (P<0.05), which was negatively correlated with WBC decline (P<0.001), suggesting that these molecules mignt be used as biomarkers of benzene-induced toxicity. Conclusions: Phenol, hydroquinone/catechol, benzenetriol and trans, trans-Muconic acid (t,t-MA) in exhaled breath of mice could be used as biomarkers for benzene exposure; ω-carboxylic fatty acid C5H10O3, ω-carboxylic fatty acid C6H12O3, glutamate, cysteine and MDA might be used as markers of benzene-induced toxicity.
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Benceno , Fenoles , Animales , Benceno/toxicidad , Biomarcadores , Masculino , Malondialdehído , Ratones , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer. PATIENTS AND METHODS: In this phase III, double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/µl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review. RESULTS: Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 [95% confidence interval (CI), 10.9-not evaluable] versus 5.4 (95% CI, 3.7-5.7) months [hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001], and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%). CONCLUSIONS: Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.
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Neoplasias Ováricas , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , China , Método Doble Ciego , Femenino , Humanos , Indazoles , Quimioterapia de Mantención , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Piperidinas , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversosRESUMEN
Objective: To explore the application value of mass spectrometry (MS) combined with next generation sequencing (NGS) in diagnosing neonatal inherited metabolic diseases (IMD). Methods: The clinical information, metabolites in blood and urine, and gene sequencing results of 19 neonates with IMD coming from the Department of Neonatology of Jiangxi Provincial Children's Hospital from March 2017 to September 2019 were analyzed retrospectively. The metabolites in blood were detected by liquid chromatography tandem mass spectrometry and urine were detected by gas chromatography-mass spectrometry respectively.Meanwhile, the whole bloods were dectected by neonatal genetic disease panel based on NGS. Results: Twelve neonates had the same results between MS and NGS among the 19, 2 had different results from MS to NGS, and 4 had no disease indication by MS but were diagnosed by NGS whose clinical phenotype were partially consistent with NGS results. One of them who did not carry out MS was considered as the diagnosis of IMD because of the detection of gene, and was followed up on this basis. Conclusion: MS could diagnose IMD relatively quickly to guide clinical treatment, and while NGS could verify the results of MS detection. Combination of MS and NGS would understand the cause of disease on genetic level, so as to guide further treatment and genetic consultation.
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Enfermedades del Recién Nacido , Enfermedades Metabólicas , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Recién Nacido , Espectrometría de Masas , Estudios RetrospectivosRESUMEN
OBJECTIVE: To study the influence of micro ribonucleic acid (miR)-155 on depression-like behaviors of depression mice, and to explore the role of Wnt/b-catenin signaling pathway in behavioral regulation of depression mice. MATERIALS AND METHODS: The mouse model of depression was established via chronic unpredictable mild stress (CUMS). All mice were randomly divided into control group (n=12), model group (n=12), and fluoxetine group (n=12). The expression level of miR-155 in the hippocampus of mice in each group was detected via quantitative Polymerase Chain Reaction (qPCR). The changes in the behaviors of mice in each group were evaluated via behavioral experiments. The apoptosis level in the hippocampus of mice in each group was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Moreover, the content of inflammatory factors in the hippocampus of mice in each group was detected using the enzyme-linked immunosorbent assay (ELISA) kits. The expression levels of Wnt/b-catenin signaling pathway-related proteins in each group were detected via Western blotting. RESULTS: The expression level of miR-155 in the hippocampus was significantly higher in model group than that in control group (p<0.01). Meanwhile, the expression level of miR-155 was significantly lower in fluoxetine group than that in model group (p<0.01). There were no statistically significant differences in the crossing score and rearing score in the open field test among groups (p>0.05). Compared with those in control group, the immobility time in tail suspension test and forced swimming test were significantly increased (p<0.01), while the sucrose preference degree significantly declined (p<0.01) in model group. Fluoxetine could significantly reduce the immobility time in tail suspension test and forced swimming test (p<0.01) and increase the sucrose preference degree (p<0.01) in model group. The number of TUNEL-positive cells in the hippocampus of mice in model group was significantly larger than that in control group (p<0.01). Fluoxetine could effectively reduce the number of TUNEL-positive cells in the hippocampus (p<0.01). Compared with those in control group, the content of tumor necrosis factor-α (TNF-a), interleukin-1b (IL-1b), and IL-6 in the hippocampus was significantly increased (p<0.01), while the content of IL-10 was significantly decreased (p<0.01) in model group. Fluoxetine could effectively reduce the content of TNF-a, IL-1b, and IL-6 (p<0.01) and increase the content of IL-10 (p<0.01). Besides, in model group, the expression levels of dishevelled-1 (DVL-1) and b-catenin in hippocampus remarkably declined (p<0.01), while the expression levels of glycogen synthase kinase-3b (GSK-3b) and adenomatous polyposis coli (APC) were remarkably increased (p<0.01) compared with those in control group. Fluoxetine could effectively lower the expressions of GSK-3b and APC in the hippocampus (p<0.01) and increase the expressions of DVL-1 and b-catenin (p<0.01) in model group. CONCLUSIONS: MiR-155 is involved in regulating the depression-like behaviors of depression mice through promoting the release of inflammatory factors and the apoptosis of hippocampal neurons. Its mechanism may be related to the inhibition of the Wnt/b-catenin signaling pathway.
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Depresión/metabolismo , MicroARNs/biosíntesis , Vía de Señalización Wnt/fisiología , beta Catenina/metabolismo , Animales , Antidepresivos de Segunda Generación/farmacología , Antidepresivos de Segunda Generación/uso terapéutico , Depresión/tratamiento farmacológico , Depresión/psicología , Fluoxetina/farmacología , Fluoxetina/uso terapéutico , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Distribución Aleatoria , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/metabolismo , Estrés Psicológico/psicología , Vía de Señalización Wnt/efectos de los fármacos , beta Catenina/antagonistas & inhibidoresRESUMEN
Objective: To explore the relationship between blood pressure load and sleep stability in hypertensive patients by cardiopulmonary coupling monitoring (CPC) and 24-hour ambulatory blood pressure monitoring. Methods: One hundred and fifty-five patients with essential hypertension were divided into high load group and low load group according to whether the blood pressure load was higher than 50%. The relationship between sleep stability and systolic blood pressure load was analyzed by logistic regression. Results: After adjusting for sex, age and body mass index (BMI), logistic regression analysis showed that stable sleep was the protective factor (OR=0.736,P=0.047) for the decrease of nocturnal blood pressure load, and unstable sleep was the risk factor for increasing day time blood pressure load (OR=1.336, P=0.037) in patients with hypertension. Conclusions: The effect of sleep stability on blood pressure load is different between day and night. Stable sleep is the protective factor of nocturnal systolic blood pressure load decrease, and unstable sleep is the harmful factor of daytime systolic blood pressure load increase. Increasing sleep stability helps to reduce systolic blood pressure load.
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Monitoreo Ambulatorio de la Presión Arterial , Hipertensión Esencial , Presión Sanguínea , Ritmo Circadiano , Humanos , SueñoRESUMEN
OBJECTIVE: To investigate the regulatory role of long non-coding ribonucleic acid (lncRNA) BRAF-activated non-coding RNA (BANCR) in rats with endometriosis (EMs) and its mechanism of action. MATERIALS AND METHODS: A total of 30 healthy, unmated, female Sprague-Dawley (SD) rats were selected and divided into sham-operation group, model group and lncRNA BANCR intervention group, and a rat model of EMs was established by means of autotransplantation. The volume of eutopic endometrium in each group of rats was measured, and hematoxylin and eosin (HE) staining was applied to detect the impacts on the pathological morphology of ectopic endometrial tissues in each group. The levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and MMP-9 in the rat serum were determined by virtue of enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR) was performed to measure the messenger RNA (mRNA) levels of extracellular signal-regulated kinase (ERK) and mitogen-activated protein kinase (MAPK) in the uterine tissues in each group of rats, and Western blotting assay was adopted to detect the levels of phosphorylated ERK and MAPK proteins in the rat uterine tissues in each group. RESULTS: Compared with those in sham-operation group, the volume of eutopic endometrium in the rats was increased markedly, the pathological morphology was poorer, and the content of VEGF, MMP-2 and MMP-9 in the serum, the mRNA levels of ERK and MAPK in the uterine tissues, and the levels of phosphorylated ERK and MAPK proteins were elevated notably in model group. The rats in lncRNA BANCR intervention group had evidently decreased volume of eutopic endometrium, improved pathological morphology and significantly declined content of serum VEGF, MMP-2 and MMP-9, ERK and MAPK mRNA levels, and phosphorylated ERK and MAPK protein levels in the uterine tissues than those in model group. CONCLUSIONS: LncRNA BANCR inhibitor can repress the development of ectopic endometrial tissues by inhibiting the generation of angiogenic factors in the EMs focus, and its mechanism may be related to the inhibition on the ERK/MAPK signaling pathway.
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Endometriosis/metabolismo , Endometrio/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Sistema de Señalización de MAP Quinasas/genética , Proteínas Proto-Oncogénicas B-raf/genética , ARN Largo no Codificante/genética , Animales , Modelos Animales de Enfermedad , Endometriosis/sangre , Endometriosis/genética , Endometrio/patología , Femenino , Metaloproteinasa 2 de la Matriz/sangre , Metaloproteinasa 9 de la Matriz/sangre , Fosforilación , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/sangreRESUMEN
With the acceleration of global urbanization, the human health impact from growing e-waste has become increasingly serious. Several regions of China are heavily polluted by e-waste, which has led to adverse health outcomes. Critical issues need to be addressed, including how to identify adverse health effects and conduct the health risk assessment for prevention. Recently, globally governmental-based regulations and enforcement of legislation regarding the export, recycling and disposal process of e-waste have made certain achievements. In this issue, we published several articles, which summarized and analyzed the relationship between e-waste pollution and adverse health effects from various aspects such as exposure analysis, adverse health outcomes, mechanisms and risk assessment. These findings could provide basic data and guidelines for health risk assessment and disease prevention of e-waste pollution in China.
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Residuos Electrónicos , Salud Global , Residuos Peligrosos , Reciclaje , Administración de Residuos/métodos , China , Exposición a Riesgos Ambientales , Salud Ambiental , Humanos , Medición de RiesgoRESUMEN
OBJECTIVE: To investigate the roles of miR-15a-3p in ovarian cancer cell growth and metastasis. PATIENTS AND METHODS: A key role of miR-15a-3p was identified via gene profiling and bioinformatics analysis. The impact of miR-15a-3p on ovarian cancer cell growth, migration and invasion was measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), wound-healing and transwell invasion assays. Bioinformatics and luciferase reporter assays were applied to identify that twist family BHLH transcription factor 1 (Twist1) was the target gene of miR-15a-3p. The miR-15a-3p level and the expression of Twist1 were detected using quantitative Real-time polymerase chain reaction (qRT-PCR) assay. The expressions of N-cadherin and E-cadherin were measured by immunofluorescence staining. Small interfering RNA targeting Twist1 and pCDNA3.1 containing Twist1 were applied to decrease and increase the expression of Twist1, respectively. RESULTS: miR-15a-3p was markedly down-regulated in ovarian cancer. Exogenous up-regulation of miR-15a-3p inhibited the growth, colony formation, migration and invasion of ovarian cancer cell in vitro. Furthermore, a xenograft model indicated that miR-15a-3p inhibited tumour growth and the metastatic potential of ovarian cancer cell in vivo. We found that Twist1 was the direct target of miR-15a-3p in ovarian cancer and that its expression was negatively correlated with the level of miR-15a-3p in ovarian cancer tissues. Up-regulation of miR-15a-3p rescued the inhibitory impact of miR-15a-3p on ovarian cancer cell growth, migration and invasion. Finally, down-regulation of Twist1 mimicked the suppressive effects of miR-15a-3p on ovarian cancer cell. CONCLUSIONS: We demonstrated that miR-15a-3p is down-regulated in ovarian cancer. Up-regulation of miR-15a-3p restrains the growth and metastasis of ovarian cancer cell by regulating Twist1.
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Proliferación Celular/genética , MicroARNs/genética , Proteínas Nucleares/metabolismo , Neoplasias Ováricas/genética , Proteína 1 Relacionada con Twist/metabolismo , Animales , Línea Celular Tumoral , Regulación hacia Abajo , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Ratones Desnudos , Metástasis de la Neoplasia , Proteínas Nucleares/genética , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , ARN Interferente Pequeño/genética , Proteína 1 Relacionada con Twist/genética , Regulación hacia Arriba , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Synergistic divergence is a rare condition characterized by complete absence of adduction that is associated with simultaneous abduction of the affected eye on attempted adduction. This causes the affected eye to move further into abduction on gaze to the normal side and results in extreme divergence of both eyes. It is sometimes referred to as exotropic Duane syndrome with synergistic divergence (type 4 Duane syndrome) or congenital fibrosis syndrome with synergistic divergence. Diseases combined with synergistic divergence fall within the category of congenital cranial dysinnervation disorders (CCDDs). The ocular associations reported with synergistic divergence are uncommon and include Horner syndrome, ocular albinism, foveal hypoplasia, Goldenhar syndrome and pupillary abnormalities. MRI and electro-oculographic study suggested that this is the result of CCDDs. Various surgical techniques have been tried in individual cases including large recession of the lateral rectus muscle, lateral rectus muscle extirpation, large resection of the medial rectus (MR) muscle, weakening procedures of the oblique muscles, combination of lateral rectus orbital wall fixation with MR resection, but further investigations with large-scale samples are needed. Recent research advances in the definition, etiology, and treatment of synergistic divergence are reviewed in this article. (Chin J Ophthalmol, 2019, 55:63-67).
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Síndrome de Retracción de Duane , Oftalmoplejía , Estrabismo , Movimientos Oculares , Humanos , Músculos Oculomotores , Estrabismo/diagnóstico , Estrabismo/terapiaRESUMEN
OBJECTIVE: Experimental autoimmune encephalomyelitis (EAE) is an animal model commonly used in research on the acute phase of multiple sclerosis (MS), but studies on the pathology and pathogenesis of EAE with a long disease course are seldom conducted. Besides its antioxidant properties, the comprehensive mechanisms through which α-lipoic acid (LA) affects EAE remain obscure. We here conducted the study to explore the possible mechanisms. MATERIALS AND METHODS: In this study, the following methods were used for investigating the effects of LA on long-term EAE: hematoxylin-eosin staining (HE) and electron microscopic examinations of pathological changes; Western blotting of ß-amyloid precursor protein (ß-APP) and myelin basic protein (MBP); Enzyme-linked immunosorbent assay (ELISA) of tumor necrosis factor-α (TNF-α), transforming growth factor-ß (TGF-ß), superoxide dismutase (SOD), malondialdehyde (MDA) as well as flow cytometry of CD4+CD25+FoxP3+ regulatory T cells (Tregs). RESULTS: The results showed: (1) diverse pathological features of long-term relapsing-remitting EAE; (2) relatively increased MBP and reduced ß-APP expression in LA recipients 180 days after onset; (3) down-regulated TNF-α and up-regulated TGF-ß levels in LA recipients 7 days after onset; (4) lower MDA and higher SOD levels in LA recipients 180 days after onset; (5) increased Treg levels in LA recipients 7 days after onset. CONCLUSIONS: Aside from oxidative stress, LA possessed anti-inflammatory and immunomodulatory effects on EAE. LA might be a promising candidate for MS treatment.
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Encefalomielitis Autoinmune Experimental/prevención & control , Fármacos Neuroprotectores/farmacología , Médula Espinal/efectos de los fármacos , Ácido Tióctico/farmacología , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/patología , Factores Inmunológicos/farmacología , Ratones Endogámicos C57BL , Proteína Básica de Mielina/metabolismo , Estrés Oxidativo/efectos de los fármacos , Médula Espinal/inmunología , Médula Espinal/metabolismo , Médula Espinal/patología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Factores de Tiempo , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Objective: To investigate the incidence rate of transjugular intrahepatic portosystemic shunt (TIPS) complications in the treatment of cirrhotic portal hypertension, and analyze the cause of complication to management methods. Methods: Data of 116 patients obtained from Zhongnan Hospital of Wuhan University were retrospectively analyzed. Portal venous pressure, routine blood test, coagulation test, liver and kidney function test, ammonia blood test, imaging and endoscopy reports were collected before and after procedure. The incidence rate of hepatic encephalopathy, gastrointestinal bleeding, ascites and shunt dysfunctions were observed. Data were expressed as mean ± Standard deviation and analyzed by t-test. A chi-squared test was used for comparison between categorical variables. Results: The success rate of TIPS operation was 97.41% (113/116). Two patients underwent prompt TIPS procedure due to active bleeding. Bleeding was successfully stopped. Portal venous pressure of 113 patients decreased from (42.73 ± 7.64) cmH(2)O to (24.92 ± 7.60) cmH(2)O, and the difference was statistically significant (P < 0.01). Twenty cases were of hepatic encephalopathy. Preoperative level of Child-pugh class C patients was more susceptible to hepatic encephalopathy within 3 months after procedure than class A and B. After TIPS procedure, there were 22 cases of gastrointestinal bleeding, 18 cases of shunt dysfunctions and 26 cases of disease related death. Conclusion: Rational patient selection strategies can effectively reduce portal venous pressure, incidence of hepatic encephalopathy, improve mid-and long-term therapeutic effects, and provide opportunities for liver transplantation.