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Hyponatremia is the most common disorder of electrolyte imbalances. It is necessary to develop new type of diuretics to treat hyponatremia without losing electrolytes. Urea transporters (UT) play an important role in the urine concentrating process and have been proved as a novel diuretic target. In this study, rat and mouse syndromes of inappropriate antidiuretic hormone secretion (SIADH) models were constructed and analyzed to determine if UTs are a promising drug target for treating hyponatremia. Experimental results showed that 100 mg/kg UT inhibitor 25a significantly increased serum osmolality (from 249.83 ± 5.95 to 294.33 ± 3.90 mOsm/kg) and serum sodium (from 114 ± 2.07 to 136.67 ± 3.82 mmol/L) respectively in hyponatremia rats by diuresis. Serum chemical examination showed that 25a neither caused another electrolyte imbalance nor influenced the lipid metabolism. Using UT-A1 and UT-B knockout mouse SIADH model, it was found that serum osmolality and serum sodium were lowered much less in UT-A1 knockout mice than in UT-B knockout mice, which suggest UT-A1 is a better therapeutic target than UT-B to treat hyponatremia. This study provides a proof of concept that UT-A1 is a diuretic target for SIADH-induced hyponatremia and UT-A1 inhibitors might be developed into new diuretics to treat hyponatremia.
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Hiponatremia , Síndrome de Secreción Inadecuada de ADH , Proteínas de Transporte de Membrana , Ratones Noqueados , Transportadores de Urea , Animales , Masculino , Ratones , Ratas , Modelos Animales de Enfermedad , Diuréticos/farmacología , Hiponatremia/tratamiento farmacológico , Hiponatremia/metabolismo , Síndrome de Secreción Inadecuada de ADH/tratamiento farmacológico , Síndrome de Secreción Inadecuada de ADH/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Ratones Endogámicos C57BL , Concentración Osmolar , Ratas Sprague-Dawley , Sodio/metabolismoRESUMEN
Actomyosin contractile force produced by myosin II molecules that bind and pull actin filaments is harnessed for diverse functions, from cell division by the cytokinetic contractile ring to morphogenesis driven by supracellular actomyosin networks during development. However, actomyosin contractility is intrinsically unstable to self-reinforcing spatial variations that may destroy the actomyosin architecture if unopposed. How cells control this threat is not established, and while large myosin fluctuations and punctateness are widely reported, the full course of the instability in cells has not been observed. Here, we observed the instability run its full course in isolated cytokinetic contractile rings in cell ghosts where component turnover processes are absent. Unprotected by turnover, myosin II merged hierarchically into aggregates with increasing amounts of myosin and increasing separation, up to a maximum separation. Molecularly explicit simulations reproduced the hierarchical aggregation which precipitated tension loss and ring fracture and identified the maximum separation as the length of actin filaments mediating mechanical communication between aggregates. In the final simulated dead-end state, aggregates were morphologically quiescent, including asters with polarity-sorted actin, similar to the dead-end state observed in actomyosin systems in vitro. Our results suggest the myosin II turnover time controls actomyosin contractile instability in normal cells, long enough for aggregation to build robust aggregates but sufficiently short to intercept catastrophic hierarchical aggregation and fracture.
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Actinas , Actomiosina , Actomiosina/metabolismo , Actinas/metabolismo , Citoesqueleto de Actina/metabolismo , Miosinas/metabolismo , Miosina Tipo II/metabolismo , Citocinesis/fisiología , Proteínas del Citoesqueleto/metabolismoRESUMEN
China faces challenges in meeting the World Health Organization (WHO)'s target of reducing hepatitis B virus (HBV) infections by 95% using 2015 as the baseline. Using Global Burden of Disease (GBD) 2019 data, joinpoint regression models were used to analyse the temporal trends in the crude incidence rates (CIRs) and age-standardized incidence rates (ASIRs) of acute HBV (AHBV) infections in China from 1990 to 2019. The age-period-cohort model was used to estimate the effects of age, period, and birth cohort on AHBV infection risk, while the Bayesian age-period-cohort (BAPC) model was applied to predict the annual number and ASIRs of AHBV infections in China through 2030. The joinpoint regression model revealed that CIRs and ASIRs decreased from 1990 to 2019, with a faster decline occurring among males and females younger than 20 years. According to the age-period-cohort model, age effects showed a steep increase followed by a gradual decline, whereas period effects showed a linear decline, and cohort effects showed a gradual rise followed by a rapid decline. The number of cases of AHBV infections in China was predicted to decline until 2030, but it is unlikely to meet the WHO's target. These findings provide scientific support and guidance for hepatitis B prevention and control.
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Hepatitis B , Masculino , Femenino , Humanos , Teorema de Bayes , Hepatitis B/epidemiología , Virus de la Hepatitis B , Incidencia , China/epidemiologíaRESUMEN
Periodontitis is a chronic inflammation caused by a bacterial infection and is intimately associated with an overactive immune response. Biomaterials are being utilized more frequently in periodontal therapy due to their designability and unique drug delivery system. However, local and systemic immune response reactions driven by the implantation of biomaterials could result in inflammation, tissue damage, and fibrosis, which could end up with the failure of the implantation. Therefore, immunological adjustment of biomaterials through precise design can reduce the host reaction while eliminating the periodontal tissue's long-term chronic inflammation response. It is important to note that macrophages are an active immune system component that can participate in the progression of periodontal disease through intricate polarization mechanisms. And modulating macrophage polarization by designing biomaterials has emerged as a new periodontal therapy technique. In this review, we discuss the role of macrophages in periodontitis and typical strategies for polarizing macrophages with biomaterials. Subsequently, we discuss the challenges and potential opportunities of using biomaterials to manipulate periodontal macrophages to facilitate periodontal regeneration.
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Materiales Biocompatibles , Inmunoterapia , Macrófagos , Periodontitis , Humanos , Periodontitis/tratamiento farmacológico , Periodontitis/terapia , Materiales Biocompatibles/química , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Animales , Inmunoterapia/métodos , Sistemas de Liberación de Medicamentos/métodosRESUMEN
BACKGROUND: Atrial cardiopathy is a proposed mechanism of embolic stroke of undetermined source (ESUS). Left atrial (LA) strain may identify early atrial cardiopathy prior to structural changes. We aim to study the associations between LA strain, ESUS, and atrial fibrillation (AF) detection in ESUS. METHODS: The study population included patients with ESUS and noncardioembolic (NCE) stroke presenting to the Rhode Island Hospital Stroke Center between January 2016 and June 2017 who underwent transthoracic echocardiography. Speckle tracking echocardiography (STE) was used to measure the three phases of LA strain (reservoir, conduit, and contractile). Binary logistic regression analysis was performed to determine the associations between LA strain and stroke subtype (ESUS vs. NCE) as well as follow-up detection of AF in ESUS patients. RESULTS: We identified 656 patients, 307 with ESUS and 349 with NCE. In binary logistic regression, the lowest tertiles of LA reservoir (adjusted OR 1.944, 95% CI 1.266-2.986, p = .002), contractile (aOR 1.568, 95% CI 1.035-2.374, p = .034), and conduit strain (aOR 2.288, 95% CI 1.448-3.613, p = .001) were more likely to be significantly associated with ESUS compared to NCE stroke. Among all ESUS patients, the lowest tertiles of LA reservoir strain (OR 2.534, 95% CI 1.029-6.236, p = .043), contractile strain (OR 2.828, 95% CI 1.158-6.903, p = .022), and conduit strain (OR 2.614, 95% CI 1.003-6.815, p = .049) were significantly associated with subsequent detection of AF. CONCLUSION: Reduced LA strain is associated with ESUS occurrence and AF detection in ESUS patients. Therefore, quantification of LA strain in ESUS patients may improve risk stratification and guide secondary prevention strategies.
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Fibrilación Atrial , Accidente Cerebrovascular Embólico , Cardiopatías , Embolia Intracraneal , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico por imagen , Accidente Cerebrovascular Embólico/complicaciones , Atrios Cardíacos/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico , Ecocardiografía , Factores de Riesgo , Embolia Intracraneal/diagnóstico por imagen , Embolia Intracraneal/complicacionesRESUMEN
OBJECTIVES: The purpose of this study was to investigate the hemodynamic consequences of thoracic endovascular aortic repair which reconstructed left subclavian artery by chimney stent (ch-TEVAR). METHODS: Two patients who underwent thoracic endovascular aortic repair (TEVAR) and left subclavian artery (LSA) reconstruction using chimney stents were selected. Preoperative and postoperative CTA images were collected to reconstruct hemodynamic models for comparing and analyzing blood pressure, blood flow velocity, and wall shear stress in the aortic arch and its major branches. Concurrently, morphological alterations and position of chimney stent were also assessed. RESULTS: After the reconstruction of LSA in ch-TEVAR, no endoleak was seen, but the stent in LSA was compressed. The blood flow velocity of the LSA increased and disordered, the pressure was reduced, and the WSS was increased. Even more, there were a large amount of turbulence found in the LSA of one case, and its LSA was blocked. CONCLUSION: Chimney stent reduces the occurrence of endoleak due to its excellent deformation ability, but the compressed stent has a greater impact on the hemodynamics of LSA and eventually leads to LSA occlusion; in order to keep the LSA unobstructed, it is necessary to pay attention to the position of the chimney stent and keep it straight and do not fold or twist. Chimney stent has little influence on the aortic arch and the rest of the aortic arch branches.
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BACKGROUND: Alar base is the basal part where the two sides of the nose and the upper lip are connected. Alar base depression affects the overall facial contour by making the nasolabial folds deepen, the nasolabial angle smaller, the center of the face flat, etc. Despite the rapid development of rhinoplasty, controversy still exists regarding the treatment of alar base depression. This systematic review aims to evaluate the efficacy and safety of two prevalent techniques-diced autologous cartilage and mass cartilage-for addressing alar base depression. METHODS: A systematic review was conducted by searching the literature published in PubMed, Embase and Web of Science, Cochrane from January 2000 to April 2023 with the key words 'alar base depression or depressed alar base' and 'alar base augmentation,' and 2 investigators independently screened the retrieved literature according to inclusion and exclusion criteria. RESULTS: A total of 269 articles were obtained through database search. After removing duplicates, reading titles and abstracts, and finally reviewing the full text, 6 articles were included in the final study, including 165 patients. CONCLUSIONS: The results demonstrate that both diced autologous cartilage and mass cartilage techniques exhibit favorable outcomes in correcting alar base depression. Diced autologous cartilage offers better malleability, lighter border contours, and a more natural appearance. On the other hand, diced autologous cartilage seems to offer superior long-term effects, while mass cartilage presents certain surgical procedural advantages. Also, compared to diced cartilage, mass cartilage may have a lower rate of long-term resorption and a lower risk of displacement. This review emphasizes the need for personalized treatment selection based on individual patient characteristics. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors. www.springer.com/00266 .
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OBJECTIVE: To investigate the application and therapeutic efficacy of a novel cartilage framework: the external septa framework in East Asian rhinoplasty. METHODS: From November 2021 to April 2023, Department of Plastic and Aesthetic (Burn) Surgery, the Second Xiangya Hospital, Central South University, treated 41 patients with autologous costal cartilage rhinoplasty using an innovation external septal framework. The surgical open approach used an inverted V-shaped trans-columellar incision and marginal incision. The sixth or seventh costal cartilage was harvested to form the nasal columella support grafts (strut), external nasal septal graft, cap grafts, and shield grafts, in which the nasal column support graft and external nasal septal graft are connected in a way of tongue in groove to form a external septum framework to support and lengthen the tip. A cap graft is used to shape the tip of the nose, the rectus abdominis fascia is used to cover the tip of the nose, and the shield grafts are used to augment the inferior lobules. ePTFE was sculpted according to the degree of augment of the nasal dorsum and implanted on the dorsal to augment the nasal dorsum. Clinical outcomes were assessed through standard facial photographs taken during the preoperative and follow-up periods, and a postoperative satisfaction survey was completed with regular follow-up using the rhinoplasty outcome evaluation scale (ROE) and visual analogue scale (VAS). Results of objective and subjective measurements before and after surgery were compared utilizing paired-sample t tests. Values of P < 0.05 were considered significant. Nasal framework's objective evaluation outcomes were assessed by measuring the patients' preoperative and postoperative nasolabial angle, nasal length, and nasal tip projection. (The distance between the pronasale and the alar-cheek junction was calculated as the tip projection.) The comparison of preoperative and postoperative nasolabial angle and nasal length was performed using the paired-sample t test, and the comparison of nasal tip projection was performed using the Wilcoxon signed rank-sum test for the comparison of paired samples. Values of P < 0 .05 were considered significant. RESULTS: A total of 41 patients were treated, including 9 males and 32 females, ranging in age from 17 to 48 years(32.8 ± 1.5 years old), In the study, an average follow-up period of 19.85 ± 4.88 months was observed (range 12-29 months). There was no long-term or short-term complication observed. The aesthetic outcome of all cases such as saddle nose, deviated nasal columella, bilateral asymmetry of the nose, bilateral nasal base depression, and bulbous tip was satisfactory. Patient satisfaction evaluation: The ROE scale was (11.85 ± 2.46) preoperatively and (17.43 ± 2.15) postoperatively. The VAS scores were (4.86 ± 1.60) preoperatively and (8.48 ± 1.25) postoperatively. The difference of ROE scale and VAS scores among the patients was statistically significant (P < 0. 05), and 88.9% of patients were satisfied following those procedures. In terms of nasolabial angle, preoperative and postoperative measurements of 41 patients were (86.11 ± 2.25)° and (98.66 ± 1.90)°, respectively, and the difference of nasolabial angle was statistically significant (P < 0.05); nasal length measurements were 39.43 ± 1.55 mm (37.95-43.51 mm) preoperatively and 42.17 ± 1.46 mm (40.23-45.62 mm) postoperatively; in terms of nasal tip projection, preoperative and postoperative measurements of median values were 1.84(1.73,2.01) cm and 2.15(2.02,2.32) cm, respectively; and the difference between preoperative and postoperative values was statistically significant (P < 0.05). CONCLUSIONS: The innovative cartilage framework-external septal framework, avoids the dissection of septa and absorption of septal cartilage with compression of ESG, it is easy to be performed, and it is also stable and strong to achieve in good aesthetic result. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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During exocytosis secretory vesicles fuse with a target membrane and release neurotransmitters, hormones, or other bioactive molecules through a membrane fusion pore. The initially small pore may subsequently dilate for full contents release, as commonly observed in amperometric traces. The size, shape, and evolution of the pore is critical to the course of contents release, but exact fusion pore solutions accounting for membrane tension and bending energy constraints have not been available. Here, we obtained exact solutions for fusion pores between two membranes. We find three families: a narrow pore, a wide pore, and an intermediate tether-like pore. For high tensions these are close to the catenoidal and tether solutions recently reported for freely hinged membrane boundaries. We suggest membrane fusion initially generates a stable narrow pore, and the dilation pathway is a transition to the stable wide pore family. The unstable intermediate pore is the transition state that sets the energy barrier for this dilation pathway. Pore dilation is mechanosensitive, as the energy barrier is lowered by increased membrane tension. Finally, we study fusion pores in nanodiscs, powerful systems for the study of individual pores. We show that nanodiscs stabilize fusion pores by locking them into the narrow pore family.
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Fusión de Membrana , Vesículas Secretoras , Humanos , Membrana Celular/metabolismo , Dilatación , Vesículas Secretoras/metabolismo , ExocitosisRESUMEN
The CCCTC-binding factor (CTCF) mediates transcriptional regulation and implicates epigenetic modifications in cancers. However, the systematically unveiling inverse regulatory relationship between CTCF and epigenetic modifications still remains unclear, especially the mechanism by which histone modification mediates CTCF binding. Here, we developed a systematic approach to investigate how epigenetic changes affect CTCF binding. Through integration analysis of CTCF binding in 30 cell lines, we concluded that CTCF generally binds with higher intensity in normal cell lines than that in cancers, and higher intensity in genome regions closed to transcription start sites. To facilitate the better understanding of their associations, we constructed linear mixed-effect models to analyze the effects of the epigenetic modifications on CTCF binding in four cancer cell lines and six normal cell lines, and identified seven epigenetic modifications as potential epigenetic patterns that influence CTCF binding intensity in promoter regions and six epigenetic modifications in enhancer regions. Further analysis of the effects in different locations revealed that the epigenetic regulation of CTCF binding was location-specific and cancer cell line-specific. Moreover, H3K4me2 and H3K9ac showed the potential association with immune regulation of disease. Taken together, our method can contribute to improve the understanding of the epigenetic regulation of CTCF binding and provide potential therapeutic targets for treating tumors associated with CTCF.
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Factor de Unión a CCCTC/metabolismo , Epigénesis Genética , Código de Histonas , Factor de Unión a CCCTC/química , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Genómica/métodos , Humanos , Especificidad de Órganos , Unión ProteicaRESUMEN
BACKGROUND: Recent studies have shown that deficient mismatch repair (dMMR) rectal cancer may be related to treatment resistance, resulting in a worse prognosis than proficient MMR (pMMR) rectal cancer. The purpose of this study was to explore whether surgery plus other treatments (radiotherapy and chemotherapy) can bring more benefits to these patients than surgery alone. METHODS: A retrospective study of 168 patients with rectal adenocarcinoma who underwent total mesorectal excision was conducted using immunohistochemical methods to determine MMR status and a propensity score matching model to minimize potential confounding factors between subgroups of patients with different treatment regimens. Kaplan-Meier analysis, log-rank tests, and Cox regression models were used to assess overall survival (OS) and disease-free survival (DFS) in patient subgroups. RESULTS: Only 6.9% (n = 168) of patients in the total cohort had dMMR rectal adenocarcinoma, and the most common cause of dMMR was a PMS2 deletion (103, 61.3%). The median DFS of the surgery alone group was 45.7 months (IQR, 40.9 to 77.8), and the median DFS of the surgery plus other treatment group was 43.9 months (IQR, 14.2 to 80.1). The surgery alone group was superior to the surgery plus other treatment group (HR, 0.16; 95% CI, 0.07 to 0.38; p = 0.005). There was no significant difference in OS (45.8 (IQR, 41.0 to 79.8) vs. 45.9 (IQR, 38.5 to 80.3)) between the two groups (HR, 0.57; 95% CI, 0.23 to 1.40; p = 0.263). CONCLUSIONS: For patients with locally advanced dMMR rectal adenocarcinoma, compared with surgery alone, surgery plus other treatment options (radiotherapy and chemotherapy) do not grant long-term survival benefits but rather shorten DFS.
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Adenocarcinoma , Neoplasias del Recto , Humanos , Estadificación de Neoplasias , Reparación de la Incompatibilidad de ADN , Estudios Retrospectivos , Pronóstico , Neoplasias del Recto/genética , Neoplasias del Recto/cirugía , Adenocarcinoma/genética , Adenocarcinoma/cirugíaRESUMEN
PURPOSE: Colorectal cancer (CRC) screening has been implemented in Tianjin, China since 2012. The objective was to estimate the neoplasia detection rate in a high-risk population by age and sex and to investigate the potential factors associated with colorectal neoplasia. PATIENTS AND METHODS: This study is based on data of the Tianjin CRC screening program from 2012 to 2020. Residents with a positive high-risk factors questionnaire (HRFQ) or a positive faecal immunochemical test (FIT) were identified as high-risk participants and were subsequently recommended for a free colonoscopy. RESULTS: A total of 4,117,897 eligible participants aged 40-74 years completed both a HRFQ and FIT, and 217,164 (5.3%) of them were identified as high-risk participants. Positive rates of preliminary screening increased with age and were higher in females than in males. For 57,971 participants undertaking colonoscopy, the detection rates of nonadvanced adenoma, advanced adenoma and CRC were 37.8%, 5.7% and 1.6%, respectively. Detection rates of advanced neoplasia increased from the age of 50 and were higher in males. For nonadvanced neoplasia, a strong increase was observed in males from the age of 40 and in females from the age of 50. Male sex had a greater impact on individuals aged 40-49 than on older individuals. Several factors including current smoking, drinking, and higher body mass index (BMI) were significantly associated with the presence of neoplasia, whereas, these associations were mainly restricted to individuals aged above 50 but not those aged 40-49 years. CONCLUSIONS: These findings support that age-specific risk stratification and sex-specific initiating ages for CRC screening should be recommended to improve the accuracy and effectiveness of current screening strategy.
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Adenoma , Neoplasias Colorrectales , Femenino , Humanos , Masculino , Detección Precoz del Cáncer , Factores de Riesgo , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Colonoscopía , Sangre Oculta , Adenoma/diagnóstico , Adenoma/epidemiología , Tamizaje MasivoRESUMEN
BACKGROUND: Sexually transmitted and blood-borne infections (STBBIs) is a major public health concern in China. This study assessed the overall trends in STBBIs to improve the comprehensive understanding of the burden of STBBIs and provide evidence for their prevention and control. METHODS: Data for the period from 2005 to 2021 were analyzed across China on infections with hepatitis B or C; syphilis; gonorrhea; and HIV infection. Trends, annual percent change (APC), and average annual percent change (AAPC) in diagnosis rate was analyzed using joinpoint regression models for the five STBBIs together or individually. RESULTS: From 2005 to 2021, the overall diagnosis rate of all five STBBIs increased, with an AAPC of 1.3% [95% confidence interval (CI) -0.5% to 3.1%]. Diagnosis rates of HIV, syphilis and hepatitis C increased individually, but it decreased for infections of hepatitis B and gonorrhea. Joinpoint analysis identified four phases in diagnosis rate of hepatitis C; three phases in diagnosis rate of hepatitis B, HIV infection, and syphilis; two in diagnosis rate of gonorrhea infection. CONCLUSION: Despite national efforts to prevent and control STBBIs, their overall diagnosis rate has continued to rise in China, and they remain an important public health challenge. Further efforts should be made to educate the general population about STBBIs, particularly HIV. Interventions targeting vulnerable groups should be adopted and their efficacy monitored through regular analysis of trends.
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Gonorrea , Infecciones por VIH , Hepatitis B , Hepatitis C , Enfermedades de Transmisión Sexual , Sífilis , Humanos , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/prevención & control , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Sífilis/epidemiología , Gonorrea/diagnóstico , Gonorrea/epidemiología , Infecciones de Transmisión Sanguínea , Hepatitis B/epidemiología , Hepatitis C/epidemiología , China/epidemiologíaRESUMEN
AIM: Both the clinical manifestation and molecular characteristics of colorectal cancer (CRC) vary according to the anatomical site. We explored the risk factors for four groups of colorectal neoplasms (CRN) at different anatomical sites. METHODS: We extracted data from the database of Tianjin Colorectal Cancer Screening Program from 2010 to 2020. According to the CRN anatomical sites, patients were divided into four groups: the proximal colon group, the distal colon group, the rectum group, and the multiple colorectal sites. Binary logistic regression analysis was used to explore the differences in risk factors of CRN at different anatomical sites. RESULTS: The numbers of patients with CRN in the proximal colon, distal colon, rectum, and multiple colorectal sites were 4023, 6920, 3657, and 7938, respectively. Male sex was associated with a higher risk from the proximal colon to the rectum. Advanced age and obesity were also significantly associated with overall colorectal CRN risk, but there were some differences between men and women. Smoking was associated with CRN risk only in the distal colon and rectum in both men and women. Frequent alcohol consumption and family history of CRC in first-degree relatives (FDRs) were associated with the risk of multisite colorectal CRN only in males. CONCLUSIONS: We observed differences in advanced age, obesity, smoking, alcohol consumption, and family history of colorectal cancer at different anatomical sites of colorectal neoplasms. These factors vary by gender.
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Neoplasias Colorrectales , Humanos , Masculino , Femenino , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/diagnóstico , Factores de Riesgo , Recto , Obesidad/complicaciones , Colonoscopía/efectos adversosRESUMEN
OBJECTIVES: With the intention of providing a reference for secondary prevention, our study provides some insight on diagnostic yield of factors influencing compliance with colonoscopy and the presence of advanced adenomas (AA). METHODS: We conducted large-scale CRC screening among local Tianjin residents aged 40-75 years between 2012 and 2019. A high-risk factor questionnaire (HRFQ) was distributed to each participant, followed by the performance of a fecal immunochemical test (FIT). Participants who tested positively for any of these items were advised to undergo a colonoscopy. Relevant basic information was collected from participants during CRC screening, and the screening data were sorted and analysed. RESULTS: A total of 5,670,924 people participated in CRC screening by the end of 2019, including 275,708 people in the high-risk group, and 74,685 (27.1%) people who underwent colonoscopy. The results of the logistic regression model demonstrated that participants with a history of mucous bloody stool (OR = 8.20, 95% CI: 7.92, 8.50, p < 0.001), chronic diarrhea (OR = 5.73, 95% CI: 5.57, 5.89, p < 0.001), and higher level of education (OR = 1.87, 95% CI: 1.80, 1.93, p < 0.001) were more likely to comply with a colonoscopy. Several factors including age (70-75 years old:OR = 3.72, 95% CI: 2.71, 5.10, p < 0.001), and FIT( +) (OR = 1.65, 95% CI: 1.42,1.90, p < 0.001) were identified to be associated with the presence of AA. CONCLUSIONS: Increased compliance with colonoscopy is urgently needed. Our findings can inform the design of future effective large-scale population-based CRC screening programmes.
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Detección Precoz del Cáncer , Neoplasias , Humanos , Anciano , Movimiento Celular , Colonoscopía , EscolaridadRESUMEN
BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers and is associated with high incidence and mortality rates worldwide. CRC has caused a tremendous loss of human health and wealth. The incidence and mortality of colorectal carcinoma are increasing in young adults. Early cancer detection and prevention are made possible through screening. At present, the faecal immunochemical test (FIT) is a noninvasive method that can be used for the large-scale clinical screening of CRC status. Therefore, this study, based on CRC screening results in Tianjin from 2012 to 2020, was conducted to analyse the major differences in diagnostic performance parameters according to sex and age. METHODS: This study was based on 39,991 colonoscopies performed for individuals in the Tianjin CRC screening program from 2012 to 2020. Of these individuals, they had complete FIT and colonoscopy results. The differences in FIT results were analysed by sex and age. RESULTS: According to this study, males were generally more likely to develop advanced neoplasms (ANs) than females, and the prevalence increased with age. Males with negative FIT results were more likely to have advanced neoplasms than females with positive results. The accuracy of the FIT in detecting ANs in each age group was 54.9%, 45.5%, 48.6% and 49.5% in the 40-49, 50-59, 60-69, and ≥ 70 age groups, respectively. CONCLUSIONS: The FIT detected ANs with highest accuracy in the 40-49 age group. Our research can provide guidance to formulate CRC screening strategies.
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Neoplasias Colorrectales , Tamizaje Masivo , Masculino , Femenino , Humanos , Adolescente , Adulto , Persona de Mediana Edad , Tamizaje Masivo/métodos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Sangre Oculta , Detección Precoz del Cáncer/métodos , Colonoscopía/métodos , HecesRESUMEN
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. Cyst development in ADPKD involves abnormal epithelial cell proliferation, which is affected by the primary cilia-mediated signal transduction in the epithelial cells. Thus, primary cilium has been considered as a therapeutic target for ADPKD. Since ADPKD exhibits many pathological features similar to solid tumors, we investigated whether targeting primary cilia using anti-tumor agents could alleviate the development of ADPKD. Twenty-four natural compounds with anti-tumor activity were screened in MDCK cyst model, and 1-Indanone displayed notable inhibition on renal cyst growth without cytotoxicity. This compound also inhibited cyst development in embryonic kidney cyst model. In neonatal kidney-specific Pkd1 knockout mice, 1-Indanone remarkably slowed down kidney enlargement and cyst expansion. Furthermore, we demonstrated that 1-Indanone inhibited the abnormal elongation of cystic epithelial cilia by promoting tubulin polymerization and significantly down-regulating expression of anterograde transport motor protein KIF3A and IFT88. Moreover, we found that 1-Indanone significantly down-regulated ciliary coordinated Wnt/ß-catenin, Hedgehog signaling pathways. These results demonstrate that 1-Indanone inhibits cystic cell proliferation by reducing abnormally prolonged cilia length in cystic epithelial cells, suggesting that 1-Indanone may hold therapeutic potential to retard cyst development in ADPKD.
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Quistes , Riñón Poliquístico Autosómico Dominante , Ratones , Animales , Riñón Poliquístico Autosómico Dominante/tratamiento farmacológico , Riñón Poliquístico Autosómico Dominante/metabolismo , Riñón Poliquístico Autosómico Dominante/patología , Cilios , Tubulina (Proteína)/metabolismo , Proteínas Hedgehog/metabolismo , Riñón/patología , Ratones Noqueados , Quistes/metabolismo , Quistes/patología , Canales Catiónicos TRPP/metabolismo , Células Epiteliales/metabolismoRESUMEN
Aquaporins (AQP) working as membrane channels facilitated water transport, play vital roles in various physiological progress including cell migration, energy metabolism, inflammation, etc. They are quite important drug targets, but elusive for discovery due to their undruggable properties. In this chapter, we summarized most fluently used methods for screening AQP inhibitors, including cell swelling assay, cell shrinking assay, and stopped-flow assay. And three classes of AQP inhibitors have been discussed, including metal-related inhibitors, quaternary ammonium salts, and small molecule inhibitors which further divided into four parts, sulfanilamide analogies, TGN-020, antiepileptic drugs, and others. It has been suggested that although they showed inhibition effects on AQP1, AQP3, AQP4, AQP7, or AQP9 in some researches, none of them could be asserted as AQP inhibitors to some extent. Discovering AQP inhibitors is a big challenge, but if successful, it will be a great contribution for human health.
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Acuaporinas , Humanos , Acuaporina 1/metabolismo , Acuaporina 3/metabolismo , Acuaporina 4/metabolismo , Acuaporinas/antagonistas & inhibidores , Acuaporinas/metabolismo , Transporte BiológicoRESUMEN
PURPOSE: This study was performed to summarize our experience in the management of early-stage acute superior mesenteric artery embolism (ASMAE) by percutaneous mechanical thrombectomy (PMT). METHODS: The clinical data of 12 patients with early-stage ASMAE treated by PMT in our institution from November 2019 to September 2021 were retrospectively analyzed. The patients had no obvious evidence of bowel infarction as shown by peritoneal puncture and computed tomography angiography. Thrombectomy of the superior mesenteric artery was performed using a 6F AngioJet catheter. RESULTS: The emboli were completely removed in 10 (83.3%) patients. Six patients were treated only by the AngioJet device. The other six patients underwent combined treatment with a 6F multipurpose drainage catheter after PMT, including one patient who underwent simultaneous stent implantation. Two patients showed no significant improvement in their symptoms after the operation; one was found to have intestinal necrosis and underwent resection by exploratory laparotomy, and the other died of septic shock 3 days after PMT (further intervention had been discontinued because of complications with multiple underlying diseases). No other PMT-related complications occurred. Only one patient was found to have a pseudoaneurysm of the superior mesenteric artery 1 week after PMT and underwent resection by exploratory laparotomy. The 11 surviving patients were smoothly discharged from the hospital after their symptoms were relieved. At a mean follow-up of 13.2 months, computed tomography angiography showed smooth patency of the superior mesenteric artery. No patients developed serious symptoms during follow-up. CONCLUSIONS: PMT by the AngioJet device is a minimally invasive, safe, and effective technique to remove ASMAE. Early application of PMT can avoid acute intestinal necrosis. Combining the AngioJet device with a 6F multipurpose drainage catheter might be more helpful to remove residual emboli.
Asunto(s)
Embolia , Arteria Mesentérica Superior , Humanos , Arteria Mesentérica Superior/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Trombectomía/efectos adversos , Embolia/etiología , Embolia/cirugía , Necrosis/etiología , Terapia Trombolítica/efectos adversosRESUMEN
Consumers and manufacturers are exposed to nanosized zinc oxide (nZnO) and silver particles (nAg) via airways, but their biological effects are still not fully elucidated. To understand the immune effects, we exposed mice to 2, 10, or 50 µg of nZnO or nAg by oropharyngeal aspiration and analyzed the global gene expression profiles and immunopathological changes in the lungs after 1, 7, or 28 days. Our results show that the kinetics of responses varied in the lungs. Exposure to nZnO resulted in the highest accumulation of F4/80- and CD3-positive cells, and the largest number of differentially expressed genes (DEGs) were identified after day 1, while exposure to nAg caused peak responses at day 7. Additionally, nZnO mainly activated the innate immune responses leading to acute inflammation, whereas the nAg activated both innate and adaptive immune pathways, with long-lasting effects. This kinetic-profiling study provides an important data source to understand the cellular and molecular processes underlying nZnO- and nAg-induced transcriptomic changes, which lead to the characterization of the corresponding biological and toxicological effects of nZnO and nAg in the lungs. These findings could improve science-based hazard and risk assessment and the development of safe applications of engineered nanomaterials (ENMs), e.g., in biomedical applications.