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Introduction: To examine the burden of rheumatoid arthritis (RA) at the global, regional, and national levels in terms of sex, age, geographic distribution, and the Socio-demographic Index (SDI). Material and methods: Using Global Burden of Disease study data, the global incidence, disability-adjusted life years (DALYs), and estimated annual percentage change (EAPC) of RA from 1990 to 2019 were analysed. Results: From 1990 to 2019, the global RA incidence and DALYs increased by 6.47% and 1.15%, respectively. Moreover, both the global age-standardized incidence rate (EAPC = 0.30; 95% confidence interval (CI): 0.25-0.34) and DALYs (EAPC = 0.12; 95% CI: 0.08-0.17) increased. The age-standardized RA incidence was substantially higher in the high-SDI regions than in the other regions. By geographical region, the largest increases in the age-standardized RA incidence and DALYs were observed in Andean Latin America. By country, the largest increase in RA incidence was observed in Equatorial Guinea (EAPC = 1.78), followed by Bhutan (EAPC = 1.54) and Peru (EAPC = 1.53). The age-standardized RA incidence was lower in men than in women. Positive correlations were found between the EAPC of the age-standardized RA incidence and the SDI. Conclusions: Increasing trends in the age-standardized RA incidence and DALYs worldwide were shown. Future strategies for RA prevention should focus on women and older adults, as well as individuals from Andean Latin America, southern Latin America, central Asia, western sub-Saharan Africa, and other high-risk regions.
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Sevoflurane (SEV), usually causing neuronal damage and cognitive dysfunction, is one of the most commonly used anesthetics in clinical practice. However, the function of Trim47 in SEV-induced neuronal impairment remains elusive. The aim of this study was to study the effect of knocking down Trim47 on the nerve injury induced by SEV. Nerve injury was induced in rats by 3% SEV, and H19-7 was used to establish a pathological model, and sh-Trim47 was transfected into H19-7 to study the function of Trim47. The effects of SEV on the expression of Trim47 in the hippocampus and cognitive function of rats were studied by neurological function score and Moris water maze (MWM). The mRNA and protein expression of TNF-α, IL-1ß and IL-6 in the cells, along with the neuronal apoptosis in the hippocampus of rats in each group were studied by TUNEL or WB. Flow cytometry was used to study the effect of knockdown of Trim47 on cell apoptosis. CCK-8 was used to detect cell viability of H19-7 cells. Finally, the potential signaling pathway affected by knockdown of Trim47 after abrogation of SEV induction was investigated by WB. The results showed that, knockdown of Trim47 ameliorated SEV-induced neurological damage and cognitive deficits, inflammation and neuronal cell apoptosis in rats, and promoted hippocampal neuronal activity. Knockdown of Trim47 can inhibit the NF-κB signaling pathway and improve neuronal cell damage and cognitive impairment induced by SEV in neonatal rats by regulating NF-κB signaling pathway, alleviating inflammatory response, and inhibiting neuronal apoptosis.
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Anestésicos por Inhalación , Apoptosis , Disfunción Cognitiva , Neuronas , Sevoflurano , Proteínas de Motivos Tripartitos , Ubiquitina-Proteína Ligasas , Animales , Ratas , Técnicas de Silenciamiento del Gen , Proteínas de Motivos Tripartitos/genética , Ubiquitina-Proteína Ligasas/genética , Sevoflurano/toxicidad , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/genética , Modelos Animales de Enfermedad , Hipocampo/efectos de los fármacos , Hipocampo/patología , Cognición/efectos de los fármacos , Anestésicos por Inhalación/toxicidad , Ratas Sprague-Dawley , Neuronas/efectos de los fármacos , Neuronas/patología , Apoptosis/efectos de los fármacos , Apoptosis/genéticaRESUMEN
Humanistic education aims to promote educated people's practical and conscious activities to enhance their humanity, cultivate ideal personalities, and realize personal and social values, to develop a humanistic spirit. The advancement of higher education in China has led to the proposal to strengthen scientific and humanistic education integration. Medicine is between science and humanities, shouldering the important task of training senior medical personnel, the quality of medical students will affect the quality of future medical and health work; thus, medical students must explore and practice humanistic education. Promoting and practicing volunteerism is a specific act of constructing spiritual civilization in the whole society, and it is also considered beneficial for improving citizens' sense of responsibility and dedication. Medical students' practice of volunteerism and help in society is a precise manifestation of humanistic care. This review summarizes medical students' exploration and practice of humanistic education in volunteering.
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Educación Médica , Estudiantes de Medicina , Humanos , Humanidades/educación , Humanismo , CurriculumRESUMEN
Sevoflurane (Sev) might cause neurotoxicity in elderly rats. However, the role of Lin28A in Sev-induced neurotoxicity remains unclear in elderly rats. In this study, elderly rats were used to construct an Sev-induced nerve injury model. Learning and memory abilities were assessed by Morris water maze (MWM) trainings; pathological alterations in hippocampal region were assessed by HE staining; neuronal apoptosis was assessed by TUNEL; related protein expression was analyzed by immunofluorescence, immunohistochemistry, and Western blotting. Results of this study showed that Sev treatment caused nerve injury and cognitive dysfunction in elderly rats, with increased neuronal apoptosis and decreased Lin28A levels. Pathological impairment and learning and memory abilities of elderly rats were significantly improved after forced overexpression of Lin28A using AAV, accompanied by decreased expression of CD68, Iba-1, and GFAP. TUNEL analysis showed that Lin28A overexpression significantly reversed Sev-induced neuronal apoptosis. Further mechanistic analysis showed that Lin28A significantly promoted SIRT1 expression, which further reversed Sev-induced Tau acetylation at lysine 280 and 686 and Tau hyperphosphorylation, thereby alleviating nerve injury and cognitive dysfunction in elderly rats. The introduction of SIRT1 inhibitor EX527 further confirmed the involvement of SIRT1 in the regulation of Lin28A in elderly rats. In conclusion, our findings demonstrated that Lin28A reduced sevoflurane-induced nerve injury and cognitive dysfunction by inhibiting Tau acetylation and phosphorylation via activating SIRT1 in elderly rats.
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Disfunción Cognitiva , Síndromes de Neurotoxicidad , Ratas , Animales , Sevoflurano/toxicidad , Fosforilación , Sirtuina 1/metabolismo , Acetilación , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/metabolismo , Apoptosis , Síndromes de Neurotoxicidad/metabolismo , Hipocampo/metabolismo , Proteínas de Unión al ARN/metabolismoRESUMEN
Evidence has shown that suppression of the activation of NLRP3 inflammasome could ameliorate surgery/sevoflurane (SEV)-induced post-operative cognitive dysfunction (POCD). However, the underlying mechanisms remain unclear. UAF1 acts as a binding partner of USP1, which inhibits the ubiquitination-mediated degradation of NLRP3, indicating that UAF1 may be implicated in POCD through regulating the NLRP3 inflammasome. Here, we studied the role of UAF1/NLRP3 in SEV-induced cognitive impairment and neurotoxicity in rats. Neonatal rats were randomly divided into control, SEV, SEV+AAV-shNC and SEV+AAV-shUAF1 (UAF1-downregulated) groups. Morris water maze (MWM) test was applied to assess cognitive impairment. TUNEL staining, qRT-PCR and ELISA were used to assess the apoptosis and inflammation markers, respectively. The levels of superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were quantified to determine oxidative stress. The results showed that SEV treatment led to significant cognitive impairment, increased apoptosis in hippocampal tissues, upregulation of MDA and inflammatory factors (TNF-α, IL-1ß, IL-18), as well as a decrease in SOD and CAT levels. All of the above observations were reversed by UAF1 downregulation. Furthermore, depletion of UAF1 neutralized SEV-mediated increase in p-NLRP3, p-IκBα and p-p65 levels. Altogether, the current study demonstrated that knockdown of UAF1 could alleviate SEV-induced cognitive impairment and neurotoxicity in rats by inhibiting pro-inflammatory signaling and oxidative stress.
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Disfunción Cognitiva , Síndromes de Neurotoxicidad , Animales , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/genética , Inflamasomas/genética , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Síndromes de Neurotoxicidad/genética , Estrés Oxidativo/genética , Ratas , Sevoflurano/toxicidad , Superóxido Dismutasa/metabolismoRESUMEN
BACKGROUND: Adolescent endometriosis is a special type of endometriosis. Its diagnosis is often delayed. This study aimed to share the treatment experience of adolescent endometriosis and analyze the clinical manifestation, clinical stage, and risk factors of postoperative recurrence in China. METHODS: Eighty-nine cases of adolescent endometriosis over 7 years in a single institution were reviewed. Demographic, clinical outcome measures were collected. RESULT: The cumulative incidence rates of postoperative recurrence at years 1, 2, 3, 4, and 5 were 13.2%, 15.09%, 16.98%, 20.75%, and 20.75%, respectively. The risk factors associated with postoperative recurrence were disease stage, number of lesions, and height. In multivariate analysis, the independent risk factors of postoperative recurrence were height (RR: 1.132, 95% CI: 1.018-1.260) and the number of pelvic lesions (three or more, RR: 4.202, 95% CI: 1.013-17.433). CONCLUSION: Taller patients and those who had multiple lesion sites (≥3) should receive more attention, because they have a higher possibility of relapse after surgery than their counterparts. This finding can guide the postoperative treatment of adolescent patients with endometrioma.
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Endometriosis , Laparoscopía , Femenino , Humanos , Adolescente , Endometriosis/cirugía , Estudios Retrospectivos , Periodo Posoperatorio , Recurrencia , Factores de Riesgo , Laparoscopía/efectos adversos , Dismenorrea/epidemiologíaRESUMEN
BACKGROUND: Type 3 fibroids are a special subtype of intramural fibroids that are likely to affect the pregnancy outcomes of assisted reproductive techniques. Hysteroscopic resection is a treatment for type 3 fibroids, but there has few study of its efficacy to date. In this study we evaluated the effect of hysteroscopic resection of type 3 fibroids on the pregnancy outcomes in infertile women. METHODS: This retrospective case-control study was conducted from January 1, 2014 to June 30, 2021. Patients who underwent IVF-ICSI in our unit were divided into a type 3 fibroid group and a hysteroscopic myomectomy group. The inclusion criteria for the type 3 fibroid group and the hysteroscopic myomectomy group were as follows: 1) age ≤ 40 years; 2) fibroid diameter or total fibroid diameter > 2.0 cm. The following exclusion criteria were used: 1) oocyte donor treatment cycles and 2) presence of chromosomal abnormalities; 3) history of other uterine surgery; 4) presence of intracavitary lesions, including submucosal fibroids; 5) single fibroid > 5.0 cm; 6) cervical fibroids; 7) unclear ultrasound description of fibroids; 8) preimplantation genetic testing was performed and 9) congenital or acquired uterine malformations. The control group in our study was selected from patients who were treated with IVF only because of fallopian tube factors. According to the age of the type 3 fibroid group and hysteroscopic myomectomy group, random sampling was carried out in the patients between 25 and 47 years of age to determine a control group. The outcomes measured included the average transfer times to live birth, cumulative clinical pregnancy rate, and cumulative live birth rate. RESULTS: A total of 302 cycles were enrolled in our study, including 125 cycles with type 3 fibroids, 122 cycles with hysteroscopic myomectomy, and 139 cycles of control patients. The average transfer times to live birth were significantly higher in the type 3 fibroid group than in the other two groups. The frequency of cumulative live births in the type 3 fibroid group was significantly lower than that in the control group. Compared with the control group, the hysteroscopic myomectomy patients had no statistically significant differences in the cumulative clinical pregnancy rate and cumulative live birth rate. CONCLUSIONS: Type 3 fibroids significantly reduced the cumulative live birth rate of IVF patients. Ultrasound-guided hysteroscopic myomectomy can be used as a treatment for type 3 fibroids and could improve the pregnancy outcomes in infertile women.
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Infertilidad Femenina , Leiomioma , Estudios de Casos y Controles , Femenino , Humanos , Infertilidad Femenina/etiología , Infertilidad Femenina/cirugía , Leiomioma/complicaciones , Leiomioma/patología , Leiomioma/cirugía , Embarazo , Resultado del Embarazo , Estudios RetrospectivosRESUMEN
INTRODUCTION: Many recent studies have conducted laparoscopic single-site surgery (LESS) using single-port laparoscopy (SPL), which combines conventional laparoscopy (CL) with a novel multichannel port. However, to implement SPL, several obstacles must be overcome. AIM: To study the clinical value of SPL in the surgical treatment of gynecological diseases. MATERIAL AND METHODS: Twenty-five patients with ectopic pregnancy (EP) and 11 with uterine leiomyoma (UL) were randomly assigned to undergo either LESS by SPL or CL. The CL was performed routinely, while the SPL was performed through a single port using a self-made, multi-channel laparoscopic approach based on CL. The following parameters were compared between the SPL and CL groups: intraoperative conditions (operation time and blood loss), postoperative conditions (exhaustion and hospital stay time), and visual analog scale. Patients with EP and those with UL were analyzed separately in this regard. In patients with UL, hemoglobin changes, complications, and long-term physical recovery within 6 months of surgery were also compared. RESULTS: The operation time was significantly longer in the SPL group than in the CL group (p < 0.001). However, blood loss, postoperative exhaustion, and hospital stay time were significantly lower (p < 0.05 in all cases). In patients with UL, intraoperative and postoperative conditions did not differ significantly between the groups. At the follow-up within 6 months, patients with UL in the SPL group had recovered, with better cosmetic effects and more satisfaction. No cases of umbilical incisional hernia occurred in the SPL group. CONCLUSIONS: SPL showed clinical efficacy, with minimal invasion, rapid recovery, and cost-effectiveness in patients with EP or UL.
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Stringent government policies, in general, and strict containment and closure policies in particular including workplace closing, restrictions on gatherings, close of public transport, stay-at-home order, restrictions on internal movement, and international travel control are associated with a lower spread rate of COVID-19 cases. On the other hand, school closures and public event cancellations have not been found to be associated with lower COVID-19 spread. Restrictions on international travel and the closing of public transport are two policies that stand out and have a consistent and slowing effect on the spread of COVID-19. The slowing effect of the containment and closure policies on the spread of COVID-19 becomes stronger one week after the policies have been implemented, consistent with the SARS-CoV-2 transmission pattern and the incubation period evolution. Furthermore, the slowing effect becomes stronger for culturally tight countries and countries with a higher population density. Our findings have important policy implications, implying that governments need to carefully implement containment and closure policies in their own countries' social and cultural contexts, with an emphasis on the ideas of the common interest, personal responsibility, and the sense of community.
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COVID-19 , Humanos , Políticas , SARS-CoV-2 , Instituciones AcadémicasRESUMEN
BACKGROUND: Although the prognosis for most patients with papillary thyroid cancer (PTC) is good, the present treatment is ineffective for 5-10% patients. Several studies found sodium-glucose cotransporter 2 (SGLT2) inhibitors may inhibit the growth of tumors. However, whether SGLT2 inhibitors have therapeutic effect on thyroid cancer remains unclear. MATERIALS AND METHODS: The levels of SGLT2 in PTC and normal thyroid tissue were assessed by immunohistochemistry and clinical dataset analysis. Cell growth was detected by the CCK-8 and colony formation. Glucose uptake into thyroid cancer cell was evaluated by 2-DG uptake assay. Glycolysis were analyzed by Seahorse XF Extracellular Flux Analysis. RNA-seq were used to screen differentially expressed genes of cells treated with/without canagliflozin (a SGLT2 inhibitor). Furthermore, flow cytometry, western blot, and gene set enrichment analysis were employed to elucidate cell cycle, apoptosis and the underlying mechanism of the anticancer effect of canagliflozin. The effect of canagliflozin on thyroid cancer growth was further confirmed in vivo through xenograft formation assay. RESULTS: SGLT2 inhibition attenuated the growth of thyroid cancer cells in vitro and in vivo. Canagliflozin inhibited glucose uptake, glycolysis and AKT/mTOR signaling activation, and increased AMPK activation in thyroid cancer cell. Furthermore, canagliflozin inhibited G1/S phase transition and cyclin D1, cyclin D3, cyclin E1, cyclin E2, and E2F1 expression levels in thyroid cancer cell. In addition, canagliflozin increased apoptosis of thyroid cancer cell. Further investigation revealed that canagliflozin could increase γ-H2AX expression levels and DNA damage response signaling ATM/CHK2 activation. In thyroid cancer patients, SGLT2 was increased in thyroid cancer and positively related to cyclin D3. CONCLUSIONS: SGLT2 inhibition may limit glucose uptake resulting in energetic crisis, following oxidative stress mediated DNA damage and cell cycle arrest, which resulted to the increased cell apoptosis and decreased proliferation of thyroid cancer cells, suggesting a potential use for SGLT2 inhibitors as thyroid cancer therapeutics.
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As a common chronic metabolic disease, the development of diabetes mellitus (DM) may also be accompanied by liver damage and inflammatory disorders. Sitagliptin is an inhibitor of dipeptidyl peptidase-4 (DPP4, also known as CD26), which is clinically used for DM treatment. However, the mechanism of sitagliptin's efficiency in liver diseases is largely unknown. In this study, mice suffering from streptozotocin (STZ) exhibit elevated liver DPP4 expression and activity, as well as inflammatory and chronic liver injury phenotype, whereas specifically inhibiting the activity of DPP4 in mouse liver tissues and hepatocytes by sitagliptin contributes to decreased cytokines, oxidative stress, cell apoptosis, and inflammation in STZ-induced diabetic mice. Moreover, sitagliptin reduced TNFα or LPS-induced cellular reactive oxygen species (ROS) level, cell apoptosis, and protein expression in the NFκB signaling pathway in HepG2 cells or primary mouse hepatocytes. Altogether, our study confirms that sitagliptin may protect liver tissue by alleviating ROS production and NFκB signaling activation, providing a putative mechanism for preventing the development of diabetic liver disease.
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Circular RNAs (circRNAs) have been shown to be associated with the occurrence and development of cervical cancer (CC). In the present study, we aimed to investigate the tumor-promoting effect of hsa_circ_0000069 (circ0000069) on CC and the mechanisms underlying its effect. We found that circ0000069 was upregulated in CC cells and tissues, and that N6-methyladenosine (m6A) modification maintained circ0000069 stability. Gain- and loss-of-function assays revealed that circ0000069 promoted CC cell proliferation and migration. miR-4426 specifically binds circ0000069 and mediates its functions in CC development. In conclusion, circ0000069 was upregulated partially due to m6A modification, which promoted cell proliferation and migration via sponging miR-4426 in CC.
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Movimiento Celular/genética , Proliferación Celular/genética , Estabilidad del ARN , ARN Circular/genética , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Adenosina/análogos & derivados , Adenosina/metabolismo , Secuencia de Bases , Carcinogénesis/genética , Línea Celular Tumoral , Femenino , Humanos , Oncogenes/genética , ARN Circular/análisis , ARN Circular/biosíntesisRESUMEN
INTRODUCTION: The efficacy of simvastatin plus metformin to treat polycystic ovary syndrome (PCOS) remained controversial. Therefore, we conducted this meta-analysis to explore the influence of simvastatin plus metformin versus metformin monotherapy on the treatment of PCOS. METHODS: We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through June 2020 and included randomized controlled trials (RCTs) assessing simvastatin plus metformin versus metformin for PCOS. This meta-analysis was performed using the random-effect model. RESULTS: Five RCTs were included in the meta-analysis. Overall, compared with metformin monotherapy for PCOS, combined treatment with simvastatin plus metformin was associated with significantly reduced total testosterone (mean difference [MD] = -0.31; 95 % confidence interval [CI] = -0.50 to -0.13; P = 0.0009), leuteinizing hormone: follicle stimulating hormone (LH:FSH) ratio (MD = -0.92; 95 % CI = -1.62 to -0.23; P = 0.009) and low-density lipoprotein (LDL) cholesterol (MD = -34.90; 95 % CI = -39.33 to -30.47; P < 0.00001), but spontaneous menses per 6 months, volume of both ovaries, body mass index (BMI) and fasting glucose were found to be similar between two groups. CONCLUSIONS: Combined treatment with simvastatin plus metformin was better to treat PCOS than metformin alone as evidenced by significantly reduced total testosterone, LH:FSH ratio and LDL cholesterol.
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Metformina , Síndrome del Ovario Poliquístico , Femenino , Humanos , Hipoglucemiantes , Metformina/uso terapéutico , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Simvastatina/uso terapéuticoRESUMEN
OBJECTIVE: To explore the neuroprotective effect and mechanism of miR-30c in rats with cerebral ischemia/reperfusion (CI/R) injury. METHODS: in vivo, miR-30c mimic was transfected before the rats were treated with CI/R injury, and the neurological damage was evaluated. The expression of miR-30c was analyzed by RT-PCR.The area of cerebral infarction and pathological damage in CI/R rats were detected by TTC, H&E, Nissl and TUNEL staining. The expression of SOX9, BNDF and NT-3 were analyzed by immunofluorescence and western blot. The target relationship between SOX9 and miR-30c was analyzed by dual- luciferase reporter assay. in vitro, miR-30c mimic, SOX9 mimic and negative control were transfected before the OGD/R model of HT22 was established. CCK8 and flow cytometry were used to analyze the effect of miR-30c on the cell viability and apoptosis of HT22 cells in OGD/R condition. The protein expression of SOX9, BNDF and NT-3 were analyzed by immunofluorescence and western blot. RESULTS: The expression of miR-30c in the CI/R rats were significantly lower than that of sham group (p < 0.05). The area of cerebral infarction and the number of pathological damage and apoptosis in hippocampus were improved by miR-30c. miR-30c reduced SOX9 expression and improved BNDF and NT-3 expression in hippocampus compared with CI/R group (p < 0.05). The results of dual-luciferase reporter showed that SOX9 was the target of miR-30c. Under OGD/R condition, miR-30c mimic promoted cell viability and reduced cell apoptosis. miR-30c decreased the expression of SOX9, which was consistent with the results of immunofluorescence. Moreover, miR-30c could increase the expression of BNDF and NT-3 in HT22 cells. After transfection of SOX9 mimic, it was found that the above effects of miR-30c were all reversed. CONCLUSION: miR-30c can improve the pathological damage of rats with CI/R injury and plays a neuroprotective role both in vivo and in vitro by targeting SOX9.
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Hipocampo/metabolismo , Infarto de la Arteria Cerebral Media/prevención & control , MicroARNs/metabolismo , Neuronas/metabolismo , Daño por Reperfusión/prevención & control , Factor de Transcripción SOX9/metabolismo , Animales , Apoptosis , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Línea Celular , Proliferación Celular , Modelos Animales de Enfermedad , Hipocampo/patología , Infarto de la Arteria Cerebral Media/genética , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Masculino , Ratones , MicroARNs/genética , Neuronas/patología , Neurotrofina 3/metabolismo , Ratas Sprague-Dawley , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Factor de Transcripción SOX9/genéticaRESUMEN
An outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. In this major outbreak, women are a special group, especially pregnant patients. Many problems faced by clinicians are still unclear and need to be solved. As the largest obstetrics and gynecology hospital in North China, here we summarize the diagnosis and treatment process and key points of obstetrics and gynecology patients in our hospital during the period of the COVID-19 pandemic, hoping to provide available information to inform care of obstetrics and gynecology patients.
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COVID-19/prevención & control , Brotes de Enfermedades/prevención & control , Obstetricia/métodos , Atención Perinatal/métodos , COVID-19/epidemiología , COVID-19/terapia , China/epidemiología , Brotes de Enfermedades/estadística & datos numéricos , Humanos , Obstetricia/tendencias , Pandemias , Atención Perinatal/tendenciasRESUMEN
Upregulation of the ATP-binding cassette (ABC) transporter is one of the most important factors leading to multidrug resistance (MDR) in several types of cancer. In the present study, we investigated the ability of rucaparib, a Poly (ADP-ribose) polymerase (PARP) inhibitor which is currently in clinical development, on overcoming ABC transporters-mediated MDR in cervical cancer cell lines. Rucaparib significantly enhanced the cytotoxic effects of a series of conventional chemotherapeutic drugs in drug resistance cervical cancer cell lines. Moreover, rucaparib significantly increased the accumulation of rhodamine 123 in doxorubicin- and paclitaxel-resistance cervical cancer cell lines. In addition, rucaparib significantly increased the accumulation of tritium-labeled chemotherapeutic drugs in drug resistance cervical cancer cells, and decrease the efflux of tritium-labeled chemotherapeutic drugs. Molecular docking study indicated that rucaparib could bind to the active site of the ABC transporters. The present study indicated that rucaparib could antagonize MDR in cervical cancer cells by blocking the function of ABC transporters. The results obtained in the present study provide the potential possibilities that the combination of rucaparib with other chemotherapeutic agents may benefit patients with cervical cancer.
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Transportadoras de Casetes de Unión a ATP/antagonistas & inhibidores , Antineoplásicos/farmacología , Resistencia a Antineoplásicos , Indoles/farmacología , Simulación del Acoplamiento Molecular , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Neoplasias del Cuello Uterino/metabolismo , Transportadoras de Casetes de Unión a ATP/química , Transportadoras de Casetes de Unión a ATP/metabolismo , Sitios de Unión , Línea Celular Tumoral , Doxorrubicina/farmacología , Sinergismo Farmacológico , Femenino , Humanos , Unión ProteicaRESUMEN
Accumulating evidence has demonstrated that the expression of long noncoding RNAs (lncRNAs) is altered in various types of cancer, which may prove beneficial for their use as biomarkers. Cervical carcinoma expressed PCNA regulatory lncRNA (CCEPR) is a recently identified lncRNA, which has an important role in regulating cell proliferation and apoptosis in cervical and bladder cancer; however, whether CCEPR is involved in the progression of ovarian cancer (OC) remains largely unclear. The aim of the present study was to determine the clinical significance of CCEPR in OC and to investigate its biological roles. Cell Counting Kit8 assay was used to analyze cell proliferation, Transwell assay was used to assess invasion, flow cytometric analysis was used to analyze apoptosis, and western blotting was used to perform mechanistic studies. CCEPR expression levels were significantly elevated in OC tissues compared with adjacent noncancer tissues. Similarly, significant increases in CCEPR expression were observed in OC cell lines (SKOV3 and OVCAR3) compared with the ovarian surface epithelial cell line, HOSEpiC. The increased expression levels of CCEPR were associated with increased invasion, higher International Federation of Gynecology and Obstetrics stage and a poorer overall survival rate. In vitro, the genetic silencing of CCEPR decreased the cell proliferation rate and invasive ability of OC cells, and promoted apoptosis. CCEPRsilenced OC cells also demonstrated decreased expression levels of four proteins involved in the Wnt/ßcatenin signaling pathway: Cyclin D1, ßcatenin, Myc and matrix metallopeptidase7. In conclusion, the present study demonstrated that increased expression levels of CCEPR may predict poor prognosis in patients with OC and contribute to the progression of OC through regulating the Wnt/ßcatenin signaling pathway.
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Progresión de la Enfermedad , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , ARN Largo no Codificante/metabolismo , Regulación hacia Arriba/genética , Vía de Señalización Wnt , Adulto , Anciano , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , ARN Largo no Codificante/genéticaRESUMEN
Angiogenesis and vasculogenic mimicry (VM) are thought to be the predominant processes ensuring tumor blood supply during the growth and metastasis of glioblastoma (GBM). Celastrol has potential anti-glioma effects, however the mechanisms underlying these effects remain unclarified. Recent studies have shown that the PI3K/Akt/mTOR signaling pathway is closely related to angiogenesis and VM formation. In the present study, we have demonstrated, for the first time, that celastrol eliminated VM formation by blocking this signaling pathway in glioma cells. By the treatment of celastrol, tumor growth was suppressed, tight junction and basal lamina structures in tumor microvasculature were disarranged in U87 glioma orthotopic xenografts in nude mice. Periodic acid Schiff (PAS)-CD31 staining revealed that celastrol inhibited both VM and angiogenesis in tumor tissues. Additionally, celastrol reduced the expression levels of the angiogenesis-related proteins CD31, vascular endothelial growth factor receptor (VEGFR) 2, angiopoietin (Ang) 2 and VEGFA, VM-related proteins ephrin type-A receptor (EphA) 2, and vascular endothelial (VE)-cadherin. Hypoxia inducible factor (HIF)-1α, phosphorylated PI3K, Akt, and mTOR were also downregulated by treatment with celastrol. In vitro, we further demonstrated that celastrol inhibited the growth, migration, and invasion of U87 and U251 cells, disrupted VM formation, and blocked the activity of PI3K, Akt, and mTOR. Collectively, our data suggest that celastrol inhibits VM formation and angiogenesis likely by regulating the PI3K/Akt/mTOR signaling pathway.
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The correlation between the concentration of interleukin (IL) 18 in follicular fluid and the pathogenesis of Polycystic Ovary Syndrome (PCOS) is unclear. Therefore, we tested the IL-18 and IL-18 binding protein (IL-18BP) levels in follicular fluid (FF) and serum in PCOS women undergoing reproductive measures and to explore their possibly correlation with PCOS. Serum and pooled follicular fluid levels of IL-18, IL-18BP and IL-18/IL-18BP ratios were evaluated in sixty patients with PCOS and sixty women with unexplained infertility undergoing in vitro fertilization. The FF IL-18 levels were increased in PCOS group than the CON group (p < 0.01), and the IL-18 levels were significantly higher in the FF than in serum in PCOS group. Furthermore, the elevated FF IL-18 levels have no correlation with the serum IL-18 levels. Additionally, the expression of IL-18 in the follicular fluid of the overweight PCOS patients was increased compared to the normal weight PCOS patients, while in the overweight patients, FF IL-18 was significantly higher in the PCOS group than in the control group. The FF IL-18 and IL-18BP may have a local involvement in the pathogenesis of PCOS. The PCOS itself and overweight will aggravate the local inflammatory response in the ovary. Further studies are needed to elucidate this issue.
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Líquido Folicular/metabolismo , Infertilidad Femenina/inmunología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Interleucina-18/metabolismo , Síndrome del Ovario Poliquístico/inmunología , Adulto , Estudios de Casos y Controles , Femenino , Fertilización In Vitro , Líquido Folicular/inmunología , Humanos , Infertilidad Femenina/sangre , Infertilidad Femenina/patología , Infertilidad Femenina/terapia , Péptidos y Proteínas de Señalización Intercelular/análisis , Interleucina-18/análisis , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/patología , Embarazo , Índice de Embarazo , Resultado del TratamientoRESUMEN
In the original publication of this article [1], there are two errors.