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1.
Small ; 20(11): e2309454, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38098368

ABSTRACT

The optimal treatment for tracheal tumors necessitates sequential tumor elimination and tracheal cartilage reconstruction. This study introduces an innovative inorganic nanosheet, MnO2 /PDA@Cu, comprising manganese dioxide (MnO2 ) loaded with copper ions (Cu) through in situ polymerization using polydopamine (PDA) as an intermediary. Additionally, a specialized methacrylic anhydride modified decellularized cartilage matrix (MDC) hydrogel with chondrogenic effects is developed by modifying a decellularized cartilage matrix with methacrylic anhydride. The MnO2 /PDA@Cu nanosheet is encapsulated within MDC-derived microneedles, creating a photothermal-controllable MnO2 /PDA@Cu-MDC microneedle. Effectiveness evaluation involved deep insertion of the MnO2 /PDA@Cu-MDC microneedle into tracheal orthotopic tumor in a murine model. Under 808 nm near-infrared irradiation, facilitated by PDA, the microneedle exhibited rapid overheating, efficiently eliminating tumors. PDA's photothermal effects triggered controlled MnO2 and Cu release. The MnO2 nanosheet acted as a potent inorganic nanoenzyme, scavenging reactive oxygen species for an antioxidant effect, while Cu facilitated angiogenesis. This intervention enhanced blood supply at the tumor excision site, promoting stem cell enrichment and nutrient provision. The MDC hydrogel played a pivotal role in creating a chondrogenic niche, fostering stem cells to secrete cartilaginous matrix. In conclusion, the MnO2 /PDA@Cu-MDC microneedle is a versatile platform with photothermal control, sequentially combining antitumor, antioxidant, pro-angiogenic, and chondrogenic activities to orchestrate precise tracheal tumor eradication and cartilage regeneration.


Subject(s)
Nanoparticles , Neoplasms , Tracheal Neoplasms , Humans , Mice , Animals , Antioxidants , Manganese Compounds , Oxides , Neoplasms/pathology , Cartilage , Hydrogels , Anhydrides
2.
Clin Radiol ; 79(8): e994-e1002, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38789330

ABSTRACT

AIM: To develop and validate a deep learning (DL) algorithm for the automated detection and classification of carotid artery plaques (CAPs) on computed tomography angiography (CTA) images. MATERIALS AND METHODS: This retrospective study enrolled 400 patients (300 in the Center Ⅰ and 100 in Ⅱ). Three radiologists co-labeled CAPs, and their revised calcification status (noncalcified, mixed, and calcified) was regarded as ground truth. Center Ⅰ patients were randomly divided into training and internal validation datasets, while Center Ⅱ patients served as the external validation dataset. Carotid artery regions were segmented using a modified 3D-UNet network, followed by CAPs detection and classification using a ResUNet-based architecture in a two-step DL system. The DL model's detection and classification performance were evaluated on the validation dataset using precision-recall curve, free-response receiver operating characteristic (fROC) curve, Cohen's kappa, and ROC curve analysis. RESULTS: The DL model had achieved 83.4% sensitivity at 3.0 false positives (FPs)/CTA scan in internal validation and 78.9% in external validation. F1-scores were 0.764 and 0.769 at the optimal threshold, and area under fROC curves were 0.756 and 0.738, respectively, indicating good overall accuracy for CAP detection. The DL model also showed good performance for the ternary classification of CAPs, with Cohen's kappa achieved 0.728 and 0.703 in both validation datasets. CONCLUSION: This study demonstrated the feasibility of using a fully automated DL-based algorithm for the detection and ternary classification of CAPs, which could be helpful for the workloads of radiologists.


Subject(s)
Computed Tomography Angiography , Deep Learning , Humans , Computed Tomography Angiography/methods , Male , Female , Retrospective Studies , Middle Aged , Aged , Carotid Stenosis/diagnostic imaging , Carotid Arteries/diagnostic imaging , Plaque, Atherosclerotic/diagnostic imaging , Carotid Artery Diseases/diagnostic imaging , Radiographic Image Interpretation, Computer-Assisted/methods , Sensitivity and Specificity
3.
Chaos ; 34(8)2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39177957

ABSTRACT

Dynamics and properties of breathers for the modified Korteweg-de Vries equations with negative cubic nonlinearities are studied. While breathers and rogue waves are absent in a single component waveguide for the negative nonlinearity case, coupling can induce regimes of modulation instabilities. Such instabilities are correlated with the existence of rogue waves and breathers. Similar scenarios have been demonstrated previously for coupled systems of nonlinear Schrödinger and Hirota equations. Both real- and complex-valued modified Korteweg-de Vries equations will be treated, which are applicable to stratified fluids and optical waveguides, respectively. One special family of breathers for coupled, complex-valued equations is derived analytically. Robustness and stability of breathers are studied computationally. Knowledge of the growth rates of modulation instability of plane waves provides an instructive prelude on the robustness of breathers to deterministic perturbations. A theoretical formulation of the linear instability of breathers will involve differential equations with periodic coefficient, i.e., a Floquet analysis. Breathers associated with larger eigenvalues of the monodromy matrix tend to suffer greater instability and increased tendency of distortion. Predictions based on modulation instability and Floquet analysis show excellent agreements. The same trend is obtained for simulations conducted with random noise disturbances. Linear approaches like modulation instabilities and Floquet analysis, thus, generate a very illuminating picture of the nonlinear dynamics.

4.
Chaos ; 34(1)2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38231179

ABSTRACT

The nonlinear Schrödinger equation possesses doubly periodic solutions expressible in terms of the Jacobi elliptic functions. Such solutions can be realized through doubly periodic patterns observed in experiments in fluid mechanics and optics. Stability and robustness of these doubly periodic wave profiles in the focusing regime are studied computationally by using two approaches. First, linear stability is considered by Floquet theory. Growth will occur if the eigenvalues of the monodromy matrix are of a modulus larger than unity. This is verified by numerical simulations with input patterns of different periods. Initial patterns associated with larger eigenvalues will disintegrate faster due to instability. Second, formation of these doubly periodic patterns from a tranquil background is scrutinized. Doubly periodic profiles are generated by perturbing a continuous wave with one Fourier mode, with or without the additional presence of random noise. Effects of varying phase difference, perturbation amplitude, and randomness are studied. Varying the phase angle has a dramatic influence. Periodic patterns will only emerge if the perturbation amplitude is not too weak. The growth of higher-order harmonics, as well as the formation of breathers and repeating patterns, serve as a manifestation of the classical problem of Fermi-Pasta-Ulam-Tsingou recurrence.

5.
Zhonghua Wai Ke Za Zhi ; 62(6): 598-605, 2024 Jun 01.
Article in Zh | MEDLINE | ID: mdl-38682632

ABSTRACT

Objective: To investigate the effect of the ratio of the maximum diameter of aneurysm sac to age (R) on the long-term efficacy of endovascular aneurysm repair (EVAR) and open surgical repair (OSR) in patients with infrarenal abdominal aortic aneurysm (IAAA). Methods: This is a retrospective cohort study.The clinical data of 317 patients with IAAA who underwent surgical repair in the Department of Vascular Surgery,the Third Affiliated Hospital of Sun Yat-Sen University from January 2016 to October 2022 were retrospectively collected.There were 266 males and 51 females,aged (69.7±8.3) years (range:37 to 87 years).The R value of the patient was calculated and the receiver operating characteristic(ROC) curve was used to establish a model to calculate the optimal cut-off value.The propensity score matching method was used to match the baseline data of patients in the EVAR and OSR group by 3∶1 (the caliper value was 0.05),and the patients were stratified according to the cutoff value of R, and the postoperative efficacy and survival of the patients were analyzed.The primary endpoint was the total mortality rate,and the secondary endpoints included the occurrence of postoperative complications and reintervention.Pearson χ2 or Fisher 's exact test was used for categorical variables, and independent sample t test or Wilcoxon rank sum test was used for continuous variables to compare differences between groups.The survival curves of the two groups were described by Kaplan-Meier method. Results: After propensity score matching,198 cases were in the EVAR group and 66 cases were in the OSR group.The ROC model showed that the best cut-off value of R value was 0.90,and the two groups were divided into two layers:R<0.90 and R≥0.90.Among them,112 patients with R<0.90 (84 cases of EVAR,28 cases of OSR);there were 152 patients with R≥0.90 (114 cases of EVAR and 38 cases of OSR).The follow-up time was (23.6±1.6) months (range:1 to 70 months).In the R≥0.90 stratification,the total mortality (26.3% vs.5.3%,χ2=7.600,P=0.006),complication rate (44.7% vs.26.3%, χ2=4.025,P=0.045), and secondary intervention rate (31.6% vs.13.2%, χ2=4.910,P=0.027) in the EVAR group were higher than those in the OSR group.In the R<0.90 stratification,there was no significant difference in the total mortality rate (13.1% vs.10.7%, χ2=0.109,P=0.741), complication rate (28.6% vs.35.7%, χ2=0.507,P=0.477) and secondary intervention rate (14.3% vs.21.4%, χ2=0.353,P=0.552) between the two groups. Conclusions: When R≥0.90 in IAAA patients,OSR maybe more beneficial to patients in terms of survival rate,postoperative complication rate and secondary intervention rate than EVAR.When R<0.90,there are no significant differences in survival rate,complication rate and secondary intervention rate between the two surgical methods.


Subject(s)
Aortic Aneurysm, Abdominal , Endovascular Procedures , Humans , Aortic Aneurysm, Abdominal/surgery , Male , Female , Retrospective Studies , Aged , Endovascular Procedures/methods , Middle Aged , Aged, 80 and over , Treatment Outcome , Adult , Blood Vessel Prosthesis Implantation/methods , Age Factors , Propensity Score , Postoperative Complications
6.
Zhonghua Yan Ke Za Zhi ; 60(10): 822-831, 2024 Oct 11.
Article in Zh | MEDLINE | ID: mdl-39375140

ABSTRACT

Objective: To comprehend the status and changing trend in the burden of refractive errors in China from 1990 to 2019, and to furnish data-driven support for the formulation of rational strategies in refractive error prevention and control. Methods: Using the Global Burden of Disease Database 2019, data on refractive error prevalence and years lived with disability (YLD) in China from 1990 to 2019 were extracted and their standardized rates were calculated. The trend of refractive error prevalence, age, period, and gender was analyzed using joinpoint regression models. Results: From 1990 to 2019, the number of cases, prevalence rate, and YLD rate of refractive errors in China showed an upward trend, which was consistent with global trends. However, the magnitude of the increase in these parameters was higher than the global average. Conversely, the age-standardized prevalence rate and age-standardized YLD rate demonstrated a declining trend, which was also consistent with global trends, but the reduction rate was less pronounced compared to global levels. Notably, all indicators for females, including prevalence and YLD, exceeded those of males. The prevalence and YLD rates of refractive errors in China increased with age. The older individuals had higher rates compared to younger individuals. In 1990, the highest prevalence and YLD rates were found in the ≥70 years group, while the lowest rates were in the <5 years group. The age group with the most substantial increase in the burden of refractive errors was the 15 to 49 years population, which remained consistent during the three decades. The joinpoint regression analysis results revealed a stage-wise fluctuation in the age-standardized prevalence and YLD rates of refractive errors in China from 1990 to 2019. Specifically, the age-standardized prevalence rate increased by 0.765% from 1990 to 2001, decreased by 0.963% from 2001 to 2014, increased by 4.214% from 2014 to 2017, and decreased by 3.029% from 2017 to 2019. In contrast, the age-standardized YLD rate decreased by 0.113% from 1990 to 1995, increased by 2.252% from 1995 to 2000, decreased by 1.102% from 2000 to 2014, increased by 4.326% from 2014 to 2017, and decreased by 5.090% from 2017 to 2019. Conclusions: The standardized prevalence of refractive errors and the standardized YLD rate in China showed a downward trend, which was less than the global average level, but the disease burden was still heavy. Gender and age emerged as significant influencing factors for the prevalence of refractive errors and YLD. It is imperative to enhance efforts in the prevention and treatment of refractive errors among the middle-aged and elderly population. Attention should also be directed towards the increasing burden in the<50 years population.


Subject(s)
Refractive Errors , Humans , China/epidemiology , Refractive Errors/epidemiology , Prevalence , Female , Male , Cost of Illness , Middle Aged , Aged , Adult
7.
Clin Radiol ; 78(8): e552-e559, 2023 08.
Article in English | MEDLINE | ID: mdl-37117048

ABSTRACT

AIM: To develop a nomogram to predict lymphovascular invasion (LVI) in gastric cancer by integrating multiphase computed tomography (CT) radiomics and clinical risk factors. MATERIALS AND METHODS: One hundred and seventy-two gastric cancer patients (121 training and 51 validation) with preoperative contrast-enhanced CT images and clinicopathological data were collected retrospectively. The clinical risk factors were selected by univariate and multivariate regression analysis. Radiomic features were extracted and selected from the arterial phase (AP), venous phase (VP), and delayed phase (DP) CT images of each patient. Clinical risk factors, radiomic features, and integration of both were used to develop the clinical model, radiomic models, and nomogram, respectively. RESULTS: Radiomic features from AP (n=6), VP (n=6), DP (n=7) CT images and three selected clinical risk factors were used for model development. The nomogram showed better performance than the AP, VP, DP, and clinical models in the training and validation datasets, providing areas under the curves (AUCs) of 0.890 (95% CI: 0.820-0.940) and 0.885 (95% CI:0.765-0.957), respectively. All models indicated good calibration, and decision curve analysis proved that the net benefit of the nomogram was superior to that of the clinical and radiomic models throughout the vast majority of the threshold probabilities. CONCLUSIONS: The nomogram integrating multiphase CT radiomics and clinical risk factors showed favourable performance in predicting LVI of gastric cancer, which may benefit clinical practice.


Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/surgery , Nomograms , Retrospective Studies , Area Under Curve , Tomography, X-Ray Computed
8.
J Dairy Sci ; 106(12): 8523-8537, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37641246

ABSTRACT

Understanding consumers' purchase behaviors is fundamental to the success of the dairy industry. With its economic importance, the Chinese market is critical to dairy producers in most countries around the world. However, understanding consumers in this market is particularly challenging, as these consumers often have a different relationship with dairy products than consumers elsewhere in the world, given the country's historical dairy-related scandals. This special relationship can be characterized by what consumer behavior researchers call "high involvement," indicating that Chinese dairy consumers often attempt to reduce the level of risk associated with buying dairy products. Surprisingly, although this relationship affects several important aspects of purchase behavior, examination of the concept of involvement in the dairy sector has not been widely considered. Of note, there is no understanding of how Chinese consumers vary in their involvement levels and their implications on their dairy purchase behaviors. Nor have there been involvement-based insights provided on how dairy companies can position their marketing strategy to suit the needs of these consumers better. Thus, this study proposes a new approach to understanding Chinese consumer dairy decisions by introducing "consumer involvement" as a segmentation tool through which individuals' behaviors can be predicated according to their involvement profile. Based on an online survey administered in Shanghai using 1,073 dairy consumers, principal component analysis confirmed involvement with dairy is a multidimensional construct with the following 4 factors: pleasure value, symbolic value, risk importance, and risk probability. A 2-step cluster analysis identified 4 consumer clusters based on their involvement profile: face-concerned dairy lover, carefree dairy consumer, cautious dairy lover, and confused dairy consumer. According to a one-way ANOVA test and cross-tabulation with χ2 test, these consumer segments behave differently in relation to the extensiveness of decision making, cue utilization, trust of information sources, and consumption behavior. The outcomes in this paper further explain why efforts to restore consumer trust for dairy products do not work among some consumers, as individuals may exhibit diverse attitudes toward such information due to their heterogeneous involvement levels. The study also provides suggestions for market practitioners and organizations to develop effective target market strategies and policies according to different consumer clusters.


Subject(s)
Consumer Behavior , Dairy Products , Humans , China , Attitude , Surveys and Questionnaires
9.
Br Poult Sci ; 64(1): 90-99, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36093974

ABSTRACT

1. In a previous high-throughput sequencing study, a novel circular RNA (circRNA) generated from a SUN domain containing ossification factor (SUCO) gene transcript (circSUCO) was differentially expressed during the embryonic muscle development. This study aimed to further explore the effect of circSUCO on chicken skeletal muscle development.2. The experiment analysed the expression patterns of circSUCO in Tianfu broilers and clarified its function in the chicken skeletal muscle satellite cells (SMSC) after circSUCO knockdown. The qPCR results showed circSUCO was highly expressed in skeletal muscle and has different expression levels during various development periods.3. Mechanistically, a series of in vitro experiments showed that circSUCO interference suppressed proliferation and differentiation of SMSC. In addition, it was observed that circSUCO competitively binds with microRNAs such as miR-15a, miR-15b-5p, and miR-15c-5p according to the dual-luciferase assay and qPCR.4. Correlation was positive between the circSUCO expression level and the ratio of the breast muscle. The results revealed that circSUCO could play a positive role in proliferation and differentiation of SMSC via sponging miR-15a, miR-15b-5p, and miR-15c-5p, hence, may contribute to skeletal muscle development in chicken.


Subject(s)
MicroRNAs , Satellite Cells, Skeletal Muscle , Animals , Chickens/genetics , Chickens/metabolism , Satellite Cells, Skeletal Muscle/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Cell Differentiation/genetics , Muscle, Skeletal/metabolism , Cell Proliferation/genetics
10.
Zhonghua Jie He He Hu Xi Za Zhi ; 46(2): 151-157, 2023 Feb 12.
Article in Zh | MEDLINE | ID: mdl-36740375

ABSTRACT

Objective: To analyze the bronchoscopic manifestations and interventional treatment of pulmonary mucormycosis. Methods: Clinical data of patients with pulmonary mucormycosis undergoing bronchoscopy and interventional therapy in 4 tertiary general hospitals in China from May 2006 to May 2022 were retrospectively analyzed and the literature on the subject were reviewed. Results: The data of 10 patients with pathologically diagnosed pulmonary mucormycosis undergoing bronchoscopy and interventional therapy were collected, including 8 males and 2 females. The patients' age ranged from 21 to 72 (44±15) years. The underlying diseases included 6 cases of diabetes ketoacidosis, 3 cases of leukemia, 1 case after operation of lung cancer. Bronchoscopy showed that white viscous necrotic matters grew along the airway and blocked the airway in 9 cases, accompanied by airway bleeding in 3 cases, bloody secretion blocked the airway in 1 case, and bronchopulmonary cavity fistula in 2 cases. The biopsy histopathology of white necrotic matters showed that many mucor filaments were tangled together which were named mucormycelium. Among the 10 patients, 9 were treated with systemic drugs, including intravenous application of amphotericin B deoxycholate in 5 cases, intravenous application of amphotericin B liposome in 4 cases, oral posaconazole in 6 cases and intravenous injection in 1 case. Local drug therapy included aerosol inhalation of amphotericin B deoxycholate in 8 cases and local perfusion under bronchoscope in 5 cases. Bronchoscopic interventional therapy was used to remove mucormycelium in the bronchus, including cryotherapy in 8 cases, biopsy forceps in 7 cases, snare treatment in 2 cases and foreign body forceps in 2 cases. All 10 patients were clinical cured and with no death. Conclusions: Pulmonary mucormycosis is more common in immunocompromised hosts. Bronchoscopy often showed mucormycelium blocking the airway. Systemic and local drug therapy combined with bronchoscopic interventional therapy can achieve good clinical efficacy.


Subject(s)
Lung Neoplasms , Mucormycosis , Male , Female , Humans , Young Adult , Adult , Middle Aged , Aged , Mucormycosis/drug therapy , Retrospective Studies , Bronchoscopy , Bronchoscopes
11.
Zhonghua Wai Ke Za Zhi ; 61(6): 511-518, 2023 Jun 01.
Article in Zh | MEDLINE | ID: mdl-37088485

ABSTRACT

Objective: To explore the development of the pancreatic surgeon technique in a high-volume center. Methods: A total of 284 cases receiving pancreatic surgery by a single surgeon from June 2015 to December 2020 were retrospectively included in this study. The clinical characteristics and perioperative medical history were extracted from the medical record system of Zhongshan Hospital,Fudan University. Among these patients,there were 140 males and 144 females with an age (M (IQR)) of 61.0 (16.8) years(range: 15 to 85 years). The "back-to-back" pancreatic- jejunal anastomosis procedure was used to anastomose the end of the pancreas stump and the jejunal wall. Thirty days after discharge,the patients were followed by outpatient follow-up or telephone interviews. The difference between categorical variables was analyzed by the Chi-square test or the CMH chi-square test. The statistical differences for the quantitative data were analyzed using one-way analysis of variance or Kruskal-Wallis H test and further analyzed using the LSD test or the Nemenyi test,respectively. Results: Intraoperative blood loss in pancreaticoduodenectomy between 2015 and 2020 were 300,100(100),100(100),100(0),100(200) and 150 (200) ml,respectively. Intraoperative blood loss in distal pancreatectomy was 250 (375),100 (50),50 (65), 50 (80),50 (50),and 50 (100) ml,respectively. Intraoperative blood loss did not show statistical differences in the same operative procedure between each year. The operative time for pancreaticoduodenectomy was respectively 4.5,5.0(2.0),5.5(0.8),5.0(1.3),5.0(3.3) and 5.0(1.0) hours in each year from 2015 to 2020,no statistical differences were found between each group. The operating time of the distal pancreatectomy was 3.8 (0.9),3.0 (1.5),3.0 (1.8),2.0 (1.1),2.0 (1.5) and 3.0(2.0) hours in each year,the operating time was obviously shorter in 2018 compared to 2015 (P=0.026) and 2020 (P=0.041). The median hospital stay in 2020 for distal pancreatectomy was 3 days shorter than that in 2019. The overall incidence of postoperative pancreatic fistula gradually decreased,with a incident rate of 50.0%,36.8%,31.0%,25.9%,21.1% and 14.8% in each year. During this period,in a total of 3,6,4,2,0 and 20 cases received laparoscopic operations in each year. The incidence of clinically relevant pancreatic fistula (grade B and C) gradually decreased,the incident rates were 0,4.8%,7.1%,3.4%,4.3% and 1.4%,respectively. Two cases had postoperative abdominal bleeding and received unscheduled reoperation. The overall rate of unscheduled reoperation was 0.7%. A patient died within 30 days after the operation and the overall perioperative mortality was 0.4%. Conclusion: The surgical training of a high-volume center can ensure a high starting point in the initial stage and steady progress of pancreatic surgeons,to ensure the safety of pancreatic surgery.


Subject(s)
Pancreatic Neoplasms , Surgeons , Male , Female , Humans , Pancreatic Fistula/surgery , Retrospective Studies , Blood Loss, Surgical , Pancreatectomy/methods , Pancreaticoduodenectomy , Postoperative Complications , Postoperative Hemorrhage , Pancreatic Neoplasms/surgery
12.
J Urban Health ; 99(3): 482-491, 2022 06.
Article in English | MEDLINE | ID: mdl-35641714

ABSTRACT

Infants born with low or high ("at-risk") birthweights are at greater risk of adverse health outcomes across the life course. Our objective was to examine whether geographic hotspots of low and high birthweight prevalence in New York City had different patterns of neighborhood risk factors. We performed census tract-level geospatial clustering analyses using (1) birthweight prevalence and maternal residential address from an all-payer claims database and (2) domains of neighborhood risk factors (socioeconomic and food environment) from national and local datasets. We then used logistic regression analysis to identify specific neighborhood risk factors associated with low and high birthweight hotspots. This study examined 2088 census tracts representing 419,025 infants. We found almost no overlap (1.5%) between low and high birthweight hotspots. The majority of low birthweight hotspots (87.2%) overlapped with a socioeconomic risk factor and 95.7% overlapped with a food environment risk factor. Half of high birthweight hotspots (50.0%) overlapped with a socioeconomic risk factor and 48.8% overlapped with a food environment risk factor. Low birthweight hotspots were associated with high prevalence of excessive housing cost, unemployment, and poor food environment. High birthweight hotspots were associated with high prevalence of uninsured persons and convenience stores. Programs and policies that aim to prevent disparities in infant birthweight should examine the broader context by which hotspots of at-risk birthweight overlap with neighborhood risk factors. Multi-level strategies that include the neighborhood context are needed to address prenatal pathways leading to low and high birthweight outcomes.


Subject(s)
Infant, Low Birth Weight , Residence Characteristics , Birth Weight , Female , Humans , Infant , Infant, Newborn , New York City/epidemiology , Pregnancy , Socioeconomic Factors
13.
Nature ; 537(7619): 229-233, 2016 09 08.
Article in English | MEDLINE | ID: mdl-27501246

ABSTRACT

Chagas disease, leishmaniasis and sleeping sickness affect 20 million people worldwide and lead to more than 50,000 deaths annually. The diseases are caused by infection with the kinetoplastid parasites Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp., respectively. These parasites have similar biology and genomic sequence, suggesting that all three diseases could be cured with drugs that modulate the activity of a conserved parasite target. However, no such molecular targets or broad spectrum drugs have been identified to date. Here we describe a selective inhibitor of the kinetoplastid proteasome (GNF6702) with unprecedented in vivo efficacy, which cleared parasites from mice in all three models of infection. GNF6702 inhibits the kinetoplastid proteasome through a non-competitive mechanism, does not inhibit the mammalian proteasome or growth of mammalian cells, and is well-tolerated in mice. Our data provide genetic and chemical validation of the parasite proteasome as a promising therapeutic target for treatment of kinetoplastid infections, and underscore the possibility of developing a single class of drugs for these neglected diseases.


Subject(s)
Chagas Disease/drug therapy , Kinetoplastida/drug effects , Kinetoplastida/enzymology , Leishmaniasis/drug therapy , Proteasome Endopeptidase Complex/drug effects , Proteasome Inhibitors/pharmacology , Proteasome Inhibitors/therapeutic use , Pyrimidines/pharmacology , Triazoles/pharmacology , Trypanosomiasis, African/drug therapy , Animals , Chagas Disease/parasitology , Chymotrypsin/antagonists & inhibitors , Chymotrypsin/metabolism , Disease Models, Animal , Female , Humans , Inhibitory Concentration 50 , Leishmaniasis/parasitology , Mice , Molecular Structure , Molecular Targeted Therapy , Proteasome Inhibitors/adverse effects , Proteasome Inhibitors/classification , Pyrimidines/adverse effects , Pyrimidines/chemistry , Pyrimidines/therapeutic use , Species Specificity , Triazoles/adverse effects , Triazoles/chemistry , Triazoles/therapeutic use , Trypanosomiasis, African/parasitology
14.
J Eur Acad Dermatol Venereol ; 36(7): 1064-1073, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35344634

ABSTRACT

BACKGROUND: Dupilumab, an antibody against interleukin-4 receptor α, has demonstrated elegant efficacy and safety profiles in patients with moderate-to-severe atopic dermatitis (AD). However, the efficacy of dupilumab varies among AD patients, and compared with the Caucasian population, the data of dupilumab for Asian people, especially Chinese AD patients, is very limited. OBJECTIVE: To investigate the efficacy and safety of dupilumab for AD in a real-world Chinese single-centre prospective cohort. METHODS: We enrolled 138 moderate-to-severe AD patients receiving dupilumab treatment at Huashan Hospital, Shanghai, China in this 16-week, single-centre, prospective, open-label study. The patients were evaluated at baseline, 2, 4, 8 and 16 weeks after first dupilumab administration for multiple physician- and patient-reported outcome measures. Blood eosinophil counts and total serum IgE were measured. RESULTS: There were early and sustained improvement in all the efficacy measures evaluated after dupilumab administration. 64.5% AD patients achieved an improvement of ≥75% in the Eczema Area and Severity Index from baseline, and 60.9% patients achieved the Investigator's Global Assessment 0/1 (or a reduction of ≥2 points from baseline) at week 16. The trunk demonstrated the most significantly decreased efficacy score [median decreased 96.24% (interquartile range, 89.04 to 100%)] compared with other body sites. Female (adjusted OR: 2.12, 95% confidence interval: 0.79-5.74) and body mass index (BMI) <24 (3.03; 1.19-7.68) were identified as potential predictive factors of good response; while age >60 (0.57; 0.10-3.28) predicted poor response. Adverse events were reported by 34.1% patients, and facial erythema (13%) and ocular symptoms (10.9%) were the most common. CONCLUSIONS: Dupilumab demonstrated favourable efficacy and well-tolerated safety in Chinese AD patients in real-world practice.


Subject(s)
Dermatitis, Atopic , Antibodies, Monoclonal, Humanized , China , Dermatitis, Atopic/diagnosis , Dermatitis, Atopic/drug therapy , Double-Blind Method , Female , Humans , Prospective Studies , Severity of Illness Index , Treatment Outcome
15.
Tech Coloproctol ; 26(7): 529-535, 2022 07.
Article in English | MEDLINE | ID: mdl-35347491

ABSTRACT

Ileocolic anastomosis is performed via extracorporeal or intracorporeal techniques in robotic right hemicolectomy. The aim of this meta-analysis was to compare the short-term outcomes of intracorporeal anastomosis (IA) and extracorporeal anastomosis (EA) for robotic right colectomy. The EMBASE, PubMed, and Cochrane Library databases were searched systematically (from inception until March 1, 2020) for randomized and non-randomized control trials reporting the short-term outcomes of IA and EA for robotic right colectomy. Five observational cohort studies involving 585 participants were included in our meta-analysis. Compared to the EA group, the IA group showed significantly longer operation time [weighted mean difference (WMD): 28.88, 95% confidence interval (CI) 13.88-43.89, p = 0.0002], lower rate of anastomotic leak (odds ratio: 0.26, 95% CI 0.08-0.85, p = 0.03), and shorter time to first flatus (WMD: - 0.57, 95% CI - 0.95 to 0.19, p = 0.003). However, pooled results revealed no difference in blood loss, complications, wound infection, incisional hernia, length of incision, and hospital stay between the IA and EA groups (p < 0.05). This meta-analysis indicated that IA was superior to EA in terms of anastomotic leak and time to first flatus, but inferior in terms of operation time. Large-scale, multicenter, randomized studies are needed to confirm our findings.


Subject(s)
Colonic Neoplasms , Laparoscopy , Robotic Surgical Procedures , Anastomosis, Surgical/adverse effects , Anastomosis, Surgical/methods , Anastomotic Leak/etiology , Anastomotic Leak/surgery , Colectomy/adverse effects , Colectomy/methods , Colonic Neoplasms/surgery , Flatulence/surgery , Humans , Laparoscopy/methods , Multicenter Studies as Topic , Observational Studies as Topic , Retrospective Studies , Robotic Surgical Procedures/adverse effects , Treatment Outcome
16.
Zhonghua Yi Xue Za Zhi ; 102(44): 3532-3536, 2022 Nov 29.
Article in Zh | MEDLINE | ID: mdl-36418252

ABSTRACT

Objective: To investigate the efficacy and safety of complete transabdominal laparoscopic nephroureterectomy in treating primary upper tract urothelial carcinoma (UTUC) for post kidney transplantation patients. Methods: The clinical data of patients with primary renal pelvis and ureter tumors after kidney transplantation in Beijing Chaoyang Hospital from May 2016 to December 2019 were retrospectively analyzed. Seventeen patients (including 9 patients in ipsilateral transplanted kidney group and 8 patients in contralateral transplanted kidney group) underwent traditional retroperitoneoscopic nephroureterectomy (TRNU), and 24 patients (including 14 patients in ipsilateral transplanted kidney group and 10 patients in contralateral transplanted kidney group) underwent complete transperitoneal laparoscopic nephroureterectomy (CTNU). The perioperative clinical indicators of all patients were recorded and analyzed, and the surgical indicators of two techniques were compared. Results: Forty-one patients [16 males and 25 females, with a median age of 57 (53, 70) years old] were finally included. The operation time in the contralateral transplanted kidney group [(95±44) min] from CTNU was significantly decreased compared with that in the ipsilateral group from CTNU [(159±49) min] and the contralateral [(196±20) min] or ipsilateral [(205±21) min] groups from TRNU (all P<0.01). The blood loss volume [(84±39) ml vs (106±44) ml vs (109±20) ml vs (112±21) ml, P=0.271] and postoperative hospital stay [(10.6±2.1) d vs (11.8±1.7) d vs (10.3±1.5) d vs (11.4±1.5) d, P=0.171] were not statistically different among these four groups. During the median follow-up of 24 months, 13 patients developed contralateral recurrence or metastasis, 8 patients developed intravesical recurrence, and 5 patients died of UTUC. Conclusions: Single-position complete transabdominal laparoscopic nephroureterectomy for the treatment of primary renal ureteral tumors after kidney transplantation has the advantage of a short operation time, without increasing intraoperative blood loss or perioperative complications. It is suitable for the treatment of urothelial carcinoma after kidney transplantation, especially for the contralateral side of the transplanted kidney.


Subject(s)
Carcinoma, Transitional Cell , Kidney Neoplasms , Kidney Transplantation , Laparoscopy , Ureteral Neoplasms , Urinary Bladder Neoplasms , Male , Female , Humans , Carcinoma, Transitional Cell/surgery , Nephroureterectomy , Urinary Bladder Neoplasms/surgery , Retrospective Studies , Nephrectomy/methods , Ureteral Neoplasms/surgery , Kidney Neoplasms/surgery , Laparoscopy/methods
17.
Zhonghua Bing Li Xue Za Zhi ; 51(9): 875-880, 2022 Sep 08.
Article in Zh | MEDLINE | ID: mdl-36097905

ABSTRACT

Objective: To investigate the clinicopathological, molecular genetic, immunohistochemical and prognostic features of spinal solitary fibrous tumor (SFT). Methods: The clinical data of 12 cases of spinal SFT in Beijing Tsinghua Changgung Hospital, Affiliated to Tsinghua University, diagnosed from January 2015 to December 2021 were collected and reclassified. The clinical data, histopathology, immunohistochemistry and molecular genetics were analyzed. Follow-up and related literature reviews were conducted. Results: Among the 12 patients, there were 5 males and 7 females; the age ranged from 31 to 73 years, with a median age of 50.5 years. All 12 cases were primary tumors, including 4 cases diagnosed at the first time and 8 recurrent cases. Among the 12 cases, 8 were WHO grade 1, 3 were WHO grade 2, and 1 was WHO grade 3. Microscopically, the spinal SFT appeared as a spindle cell tumor, the stroma was rich in many thin-walled blood vessels with various histological features such as cell morphology and necrosis according to the different tumor grade. All (12/12) of the cases expressed vimentin and STAT6 (diffuse and strong nuclear stain), 11 cases (11/12) expressed both CD34 and bcl-2, and 7 cases (7/12) expressed CD99. Next-generation sequencing showed that 12 (12/12) of the patients had NAB2-STAT6 gene fusion. The 12 patients were followed up for 6 to 80 months. There were no recurrences or metastases in the 4 first cases after operation. Among the 8 recurrent cases, 2 of the patients relapsed and 2 died. Conclusions: Spinal SFT is rare and has a high recurrence tendency. Many aspects need to be considered in the diagnosis process. STAT6 is a relatively specific marker for the diagnosis of this tumor. Complete surgical resection is the preferred treatment while postoperative radiotherapy is recommended to reduce tumor recurrence.


Subject(s)
Solitary Fibrous Tumors , Adult , Aged , Female , Humans , Immunohistochemistry , Male , Middle Aged , Prognosis , Solitary Fibrous Tumors/diagnosis , Solitary Fibrous Tumors/genetics , Solitary Fibrous Tumors/surgery
18.
J Pediatr ; 229: 118-126.e1, 2021 02.
Article in English | MEDLINE | ID: mdl-33068567

ABSTRACT

OBJECTIVE: To assess the Uniformed Services Constipation Action Plan (USCAP) as an evidence-based, personalized, clinical action tool with pictograms to aid clinicians and families in the management of functional constipation. STUDY DESIGN: The USCAP facilitates the management functional constipation by using a health literacy-informed approach to provide instructions for pharmacotherapies and lifestyle modifications. This study included part 1 (pictogram validation) and part 2 (assessment). For part 1, pictogram transparency, translucency, and recall were assessed by parent survey (transparency ≥85%, mean translucency score ≥5, recall ≥85% required for validation). For part 2, the USCAP was assessed by parents, clinical librarians, and clinicians. Parental perceptions (n = 65) were assessed using the Consumer Information Rating Form (17 questions) to gauge comprehensibility, design quality and usefulness. Readability was assessed by 5 formulas and a Readability Composite Score was calculated. Clinical librarians (n = 3) used the Patient Education Materials Assessment Tool to measure understandability (19 questions) and actionability (7 questions) (>80% rating was acceptable). Suitability was assessed by clinicians (n = 34) using Doak's Suitability Assessment of Materials (superior ≥70% rating). RESULTS: All 12 pictograms demonstrated appropriate transparency, translucency, and recall. Parental perceptions reflected appropriate comprehensibility, design quality, and usefulness. The Readability Composite Score was consistent with a fifth-grade level. Clinical librarians reported acceptable understandability and actionability. Clinicians reported superior suitability. CONCLUSIONS: The USCAP met all criteria for clinical implementation and future study of USCAP implementation for treating children with chronic functional constipation.


Subject(s)
Constipation/therapy , Health Communication/methods , Patient Education as Topic , Adult , Child , Comprehension , Health Literacy , Humans , Middle Aged , Parents/education , Sampling Studies , Surveys and Questionnaires
19.
J Biol Regul Homeost Agents ; 35(1): 71-83, 2021.
Article in English | MEDLINE | ID: mdl-33511814

ABSTRACT

Asthma is an inflammatory pulmonary illness that plagues infants and young children. We carried out this investigation to examine the role of long noncoding RNA (lncRNA) RNA component of mitochondrial RNA processing endoribonuclease (RMRP) in an asthmatic mouse model induced by ovalbumin (OVA) and human airway smooth muscle cells (ASMCs). Eight-week-old mice were sensitized with OVA to simulate pediatric asthma. The expression patterns of RMRP, microRNA-206 (miR-206) and C-C motif ligand 2 (CCL2) in pulmonary tissues were evaluated by qPCR. In addition, the concentrations of interleukin (IL)-4, IL-5 and IL-13 cytokines in bronchoalveolar lavage fluid were detected by ELISA. The expression of RMRP and CCL2 was elevated, while miR-206 was reduced in OVA-induced mice. Our findings indicated that administration of RMRP overexpression in ASMCs increased the levels of biomarkers in asthma. RMRP functioned as a sponge for miR-206 to upregulate CCL2 expression. Blockade of the TGF-ß/Smad2 signaling pathway in ASMCs overexpressing RMRP suppressed the inflammatory cytokines and cell viability, while enhancing apoptosis. The RMRP/miR-206/CCL2 regulatory axis is implicated in the occurrence of pediatric asthma.


Subject(s)
Asthma , Animals , Apoptosis , Asthma/genetics , Bronchoalveolar Lavage Fluid , Chemokine CCL2 , Disease Models, Animal , Mice , Mice, Inbred BALB C , MicroRNAs/genetics , Myocytes, Smooth Muscle , RNA, Long Noncoding/genetics
20.
J Endocrinol Invest ; 44(9): 1947-1959, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33559847

ABSTRACT

PURPOSE: Growth hormone-secreting pituitary adenomas (GH-PAs) are common subtypes of functional PAs. Invasive GH-PAs play a key role in restricting poor outcomes. The transcriptional changes in GH-PAs were evaluated. METHODS: In this study, the transcriptome analysis of six different GH-PA samples was performed. The functional roles, co-regulatory network, and chromosome location of differentially expressed (DE) genes in invasive GH-PAs were explored. RESULTS: Bioinformatic analysis revealed 101 DE mRNAs and 70 DE long non-coding RNAs (lncRNAs) between invasive and non-invasive GH-PAs. Functional enrichment analysis showed that epithelial cell differentiation and development pathways were suppressed in invasive GH-PAs, whereas the pathways of olfactory transduction, retinol metabolism, drug metabolism-cytochrome P450, and metabolism of xenobiotics by cytochrome P450 had an active trend. In the protein-protein interaction network, 11 main communities were characterized by cell- adhesion, -motility, and -cycle; transport process; phosphorus and hormone metabolic processes. The SGK1 gene was suggested to play a role in the invasiveness of GH-PAs. Furthermore, the up-regulated genes OR51B6, OR52E4, OR52E8, OR52E6, OR52N2, MAGEA6, MAGEC1, ST8SIA6-AS1, and the down-regulated genes GAD1-AS1 and SPINT1-AS1 were identified in the competing endogenous RNA network. The RT-qPCR results further supported the aberrant expression of those genes. Finally, the enrichment of DE genes in chromosome 11p15 and 12p13 regions were detected. CONCLUSION: Our findings provide a new perspective for studies evaluating the underlying mechanism of invasive GH-PAs.


Subject(s)
Biomarkers , Gene Expression Regulation, Neoplastic/genetics , Growth Hormone-Secreting Pituitary Adenoma/diagnosis , Metabolic Networks and Pathways , Pituitary Neoplasms/diagnosis , RNA, Long Noncoding/analysis , RNA, Messenger/analysis , Adolescent , Adult , Chromosomes, Human, Pair 11/genetics , Chromosomes, Human, Pair 12/genetics , Cytochrome P-450 Enzyme System/metabolism , Female , Gene Expression Profiling , Growth Hormone-Secreting Pituitary Adenoma/genetics , Growth Hormone-Secreting Pituitary Adenoma/metabolism , Humans , Male , Middle Aged , Pituitary Neoplasms/metabolism , RNA, Long Noncoding/genetics , RNA, Messenger/genetics , Smell , Vitamin A/metabolism , Xenobiotics/metabolism
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