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Social isolation was associated with emotional problems (depression and anxiety) among older adults, however, little is known in China. Thus, we conducted a cross-sectional study including 6,664 ≥ 65 years older adults in Ningbo, China. We collected data on social isolation, depression, and anxiety by specific scales. The relationship between social isolation and emotional problems was estimated by multivariate-adjusted logistic regression models. The population-attributable risk percentage (PAR%) was used to explore the contribution of social isolation to emotional problems. Overall, the percentage of participants who had experienced social isolation, depression, and anxiety was 12.67%, 4.83%, and 2.63%. Compared with the elderly without social isolation, the adjusted odds ratios (95% confidence interval) of depression and anxiety with social isolation were 1.77 (1.25-2.51) and 1.66 (1.05-2.63), respectively. The PAR analysis showed that 10.66% of depression and 9.03% of anxiety could be attributable to social isolation. In the gender subgroup, ORs and PAR% were only significantly observed in female participants. In Chinese older adults, social isolation has been linked to depression and anxiety, suggesting the importance of taking effective and feasible interventions to reduce social isolation and emotional problems, especially among females.
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Ansiedade , Depressão , Isolamento Social , Humanos , Isolamento Social/psicologia , Idoso , Masculino , Feminino , China/epidemiologia , Depressão/epidemiologia , Depressão/psicologia , Ansiedade/epidemiologia , Ansiedade/psicologia , Estudos Transversais , Idoso de 80 Anos ou maisRESUMO
Cardenolides are a class of steroidal glycoside compounds that are mainly distributed in plants, have significant physiological activity in the heart, and have been used clinically for over 200 years. To provide a reference for further research and development of these compounds, the phytochemical and biological properties of natural cardenolides (295 compounds in total) isolated between 2010 and 2023 from 17 families and hundreds of species belonging to 70-80 genera were reviewed. In vitro and in vivo studies have indicated that antitumor, antibacterial, and antiviral activities are the most commonly reported pharmacological properties of cardenolides. Antitumor activities have been thoroughly studied to understand their structure-activity relationships, revealing numerous potential anticancer molecules that lay the theoretical foundation for further development of traditional Chinese medicinal herbs and the creation of new drugs.
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Mental stress, a human's common emotion that is difficult to recognize and describe, can give rise to serious psychological disorders. Skin and sweat are easily accessible sources of biomarkers and bio-signals that contain information about mental stress. It is challenging for current wearable devices to monitor psychological stress in real-time with a non-invasive manner. Therefore, we have developed a smartwatch integrated with a sweat cortisol sensor and a heart rate variation (HRV) sensor. This smartwatch can simultaneously record the cortisol levels in sweat and HRV index in real time over a long period. The cortisol sensors based on organic electrochemical transistor (OECT) are fabricated by utilizing the Prussian-blue (PB) doped molecular imprinting polymer (MIP) modified gate electrode. The sensor signal current will decrease following the combination of sweat cortisol, due to the blocking of the PBMIP conductive path, demonstrating good sensitivity, selectivity, and stability. The HRV sensor is manufactured by a photoplethysmography method. We have integrated the two sensors into a wearable smartwatch that can match well with the mobile phone APP and the upper computer software. Through the use of this smartwatch, we have observed a negative correlation between cortisol levels in sweat and the HRV index in short-term stressful environments. Our research presents a great progress in real-time and non-invasive monitoring human's stress levels, which promotes not only the stress management, but also better psychological research.
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Epithelial ovarian cancer is one of the most lethal gynecologic malignancies and poses a considerable threat to women's health. Although the progression-free survival of patients has been prolonged with the application of anti-angiogenesis drugs and Poly (ADP-ribose) polymerases (PARP) inhibitors, overall survival has not substantially improved. Thus, new therapeutic strategies are essential for the treatment of ovarian cancer. Nitazoxanide (NTZ), an FDA-approved anti-parasitic drug, has garnered attention for its potential anti-cancer activity. However, the anti-tumor effects and possible underlying mechanisms of NTZ on ovarian cancer remain unclear. In this study, we investigated the anti-tumor effects and the mechanism of NTZ on ovarian cancer in vitro and in vivo. We found that NTZ inhibited the proliferation of A2780 and SKOV3 epithelial ovarian cancer cells in a time- and concentration-dependent manner; Furthermore, NTZ suppressed the metastasis and invasion of A2780 and SKOV3 cells in vitro, correlating with the inhibition of epithelial-mesenchymal transition; Additionally, NTZ suppressed the Hippo/YAP/TAZ signaling pathway both in vitro and in vivo and demonstrated a good binding activity with core genes of Hippo pathway, including Hippo, YAP, TAZ, LATS1, and LATS2. Oral administration of NTZ inhibited tumor growth in xenograft ovarian cancer mice models without causing considerable damage to major organs. Overall, these data suggest that NTZ has therapeutic potential for treating epithelial ovarian cancer.
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Antineoplásicos , Carcinoma Epitelial do Ovário , Proliferação de Células , Transição Epitelial-Mesenquimal , Camundongos Nus , Nitrocompostos , Neoplasias Ovarianas , Tiazóis , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Nitrocompostos/farmacologia , Animais , Humanos , Tiazóis/farmacologia , Tiazóis/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/patologia , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Camundongos , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Movimento Celular/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Two previously uncharacterized compounds, an aconitine-type C19-diterpenoid alkaloid (1) and a napelline-type diterpenoid alkaloid C20-diterpenoid alkaloid (2), as well as ten known compounds (3-12), were isolated from Aconitum pendulum. Their structures were elucidated based on spectroscopic data, including 1D and 2Dâ NMR, IR, HR-ESI-MS, and single-crystal X-ray diffraction analysis. The anti-insecticidal activities of these compounds were evaluated by contact toxicity tests against two-spotted spider mites, and compounds 1, 2, and 9 showed moderate contact toxicity, with LC50 values of 0.86±0.09, 0.95±0.23, and 0.89±0.19â mg/mL, respectively. This study highlights the potential use of diterpenoid alkaloids as natural plant-derived pesticides for the management of plant pests.
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Aconitum , Alcaloides , Diterpenos , Aconitum/química , Diterpenos/química , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Tetranychidae/efeitos dos fármacos , Estrutura Molecular , Conformação Molecular , Cristalografia por Raios X , Inseticidas/química , Inseticidas/isolamento & purificação , Inseticidas/farmacologia , Modelos MolecularesRESUMO
Molecular detection of nucleic acid plays an important role in early diagnosis and therapy of disease. Herein, a novel and enhanced electrochemical biosensor was exploited based on target-activated CRISPR/Cas12a system coupling with nanoparticle-labeled covalent organic frameworks (COFs) as signal reporters. Hollow spherical COFs (HCOFs) not only served as the nanocarriers of silver nanoparticles (AgNPs)-DNA conjugates for enhanced signal output but also acted as three-dimensional tracks of CRISPR/Cas12a system to improve the cleavage accessibility and efficiency. The presence of target DNA triggered the trans-cleavage activity of the CRISPR/Cas12a system, which rapidly cleaved the AgNPs-DNA conjugates on HCOFs, resulting in a remarkable decrease of the electrochemical signal. As a proof of concept, the fabricated biosensing platform realized highly sensitive and selective detection of human papillomavirus type 16 (HPV-16) DNA ranging from 100 fM to 1 nM with the detection limit of 57.2 fM. Furthermore, the proposed strategy provided a versatile and high-performance biosensor for the detection of different targets by simple modification of the crRNA protospacer, holding promising applications in disease diagnosis.
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Técnicas Biossensoriais , Sistemas CRISPR-Cas , DNA Viral , Técnicas Eletroquímicas , Papillomavirus Humano 16 , Nanopartículas Metálicas , Estruturas Metalorgânicas , Prata , Técnicas Biossensoriais/métodos , Humanos , Nanopartículas Metálicas/química , Técnicas Eletroquímicas/métodos , Prata/química , Estruturas Metalorgânicas/química , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/isolamento & purificação , DNA Viral/análise , DNA Viral/genética , Limite de DetecçãoRESUMO
High-performance tactile sensors with skin-sensing properties are crucial for intelligent perception in next-generation smart devices. However, previous studies have mainly focused on the sensitivity and response range of tactile sensation while neglecting the ability to recognize object softness. Therefore, achieving a precise perception of the softness remains a challenge. Here, we report an integrated tactile sensor consisting of a central hole gradient structure pressure sensor and a planar structure strain sensor. The recognition of softness and tactile perception is achieved through the synergistic effect of pressure sensors that sense the applied pressure and strain sensors that recognize the strain of the target object. The results indicate that the softness evaluation parameter (SC) of the integrated structural tactile sensor increases from 0.14 to 0.47 along with Young's modulus of the object decreasing from 2.74 to 0.45 MPa, demonstrating accurate softness recognition. It also exhibits a high sensitivity of 10.55 kPa-1 and an ultrawide linear range of 0-1000 kPa, showing an excellent tactile sensing capability. Further, an intelligent robotic hand system based on integrated structural tactile sensors was developed, which can identify the softness of soft foam and glass and grasp them accurately, indicating human skin-like sensing and grasping capabilities.
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Robótica , Tato , Humanos , Robótica/instrumentação , Pele , Dispositivos Eletrônicos Vestíveis , Módulo de Elasticidade , PressãoRESUMO
Background: Niraparib significantly prolonged progression-free survival versus placebo in patients with platinum-sensitive, recurrent ovarian cancer (PSROC), regardless of germline BRCA mutation (gBRCAm) status, in NORA. This analysis reports final data on overall survival (OS). Methods: This randomised, double-blind, placebo-controlled, phase 3 trial enrolled patients across 30 centres in China between 26 September 2017 and 2 February 2019 (clinicaltrials.gov, NCT03705156). Eligible patients had histologically confirmed, recurrent, (predominantly) high-grade serous epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma (no histological restrictions for those with gBRCAm) and had received ≥2 prior lines of platinum-based chemotherapy. Patients were randomised (2:1) to receive niraparib or placebo, with stratification by gBRCAm status, time to recurrence following penultimate platinum-based chemotherapy, and response to last platinum-based chemotherapy. Following a protocol amendment, the starting dose was individualised: 200 mg/day for patients with bodyweight <77 kg and/or platelet count <150 × 103/µL at baseline and 300 mg/day otherwise. OS was a secondary endpoint. Findings: Totally, 265 patients were randomised to receive niraparib (n = 177) or placebo (n = 88), and 249 (94.0%) received an individualised starting dose. As of 14 August 2023, median follow-up for OS was 57.9 months (IQR, 54.8-61.6). Median OS (95% CI) with niraparib versus placebo was 51.5 (41.4-58.9) versus 47.6 (33.3-not evaluable [NE]) months, with hazard ratio [HR] of 0.86 (95% CI, 0.60-1.23), in the overall population; 56.0 (36.1-NE) versus 47.6 (31.6-NE) months, with HR of 0.86 (95% CI, 0.46-1.58), in patients with gBRCAm; and 46.5 (41.0-NE) versus 46.9 (31.8-NE) months, with HR of 0.87 (95% CI, 0.56-1.35), in those without. No new safety signals were identified, and myelodysplastic syndromes/acute myeloid leukaemia occurred in three (1.7%) niraparib-treated patients. Interpretation: Niraparib maintenance therapy with an individualised starting dose demonstrated a favourable OS trend versus placebo in PSROC patients, regardless of gBRCAm status. Funding: Zai Lab (Shanghai) Co., Ltd; National Major Scientific and Technological Special Project for "Significant New Drugs Development" in 2018, China [grant number 2018ZX09736019].
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Single-crystal metal foils with high-index facets are currently being investigated owing to their potential application in the epitaxial growth of high-quality van der Waals film materials, electrochemical catalysis, gas sensing, and other fields. However, the controllable synthesis of large single-crystal metal foils with high-index facets remains a great challenge because high-index facets with high surface energy are not preferentially formed thermodynamically and kinetically. Herein, single-crystal nickel foils with a series of high-index facets are efficiently prepared by applying prestrain energy engineering technique, with the largest single-crystal foil exceeding 5×8 cm2 in size. In terms of thermodynamics, the internal mechanism of prestrain regulation on the formation of high-index facets is proposed. Molecular dynamics simulation is utilized to replicate and explain the phenomenon of multiple crystallographic orientations resulting from prestrain regulation. Additionally, large-sized and high-quality graphite films are successfully fabricated on single-crystal Ni(012) foils. Compared to the polycrystalline nickel, the graphite/single-crystal Ni(012) foil composites show more than five-fold increase in thermal conductivity, thereby showing great potential applications in thermal management. This study hence presents a novel approach for the preparation of single-crystal nickel foils with high-index facets, which is beneficial for the epitaxial growth of certain two-dimensional materials.
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BACKGROUND: MicroRNA (miRNA) emerges as important cancer biomarker, accurate detection of miRNA plays an essential role in clinical sample analysis and disease diagnosis. However, it remains challenging to realize highly sensitive detection of low-abundance miRNA. Traditional detection methods including northern blot and real-time PCR have realized quantitative miRNA detection. However, these detection methods are involved in sophisticated operation and expensive instruments. Therefore, the development of novel sensing platform with high sensitivity and specificity for miRNA detection is urgently demanded for disease diagnosis. RESULTS: In this work, a novel electrochemical biosensor was constructed for miRNA detection based on target-driven cascade amplified assembly of electroactive covalent organic frameworks (COFs) on tetrahedral DNA nanostructure with multiplex recognition domains (m-TDN). COFs were employed as nanocarriers of electroactive prussian blue (PB) molecules by the "freeze-drying-reduction" method without the use of DNA as gatekeeper, which was simple, mild and efficient. The target-triggered catalytic hairpin assembly (CHA) and glutathione reduction could convert low-abundance miRNA into a large amount of Mn2+. Without the addition of exogenous Mn2+, the dynamically-generated Mn2+-powered DNAzyme cleavage process induced abundant PB-COFs probe assembled on the four recognition domains of m-TDN, resulting in significantly signal output. Using miRNA-182-5p as the model target, the proposed electrochemical biosensor achieved ultrasensitive detection of miRNA-182-5p in the range of 10 fM-100 nM with a detection limit of 2.5 fM. SIGNIFICANCE AND NOVELTY: Taking advantages of PB-COFs probe as the enhanced signal labels, the integration of CHA, Mn2+-powered DNAzyme and m-TDN amplification strategy significantly improved the sensitivity and specificity of the biosensor. The designed sensing platform was capable of miRNA detection in complex samples, which provided a new idea for biomarker detection, holding promising potential in clinical diagnosis and disease screening.
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Técnicas Biossensoriais , DNA Catalítico , DNA , Técnicas Eletroquímicas , Estruturas Metalorgânicas , MicroRNAs , Nanoestruturas , MicroRNAs/análise , Estruturas Metalorgânicas/química , Técnicas Biossensoriais/métodos , Nanoestruturas/química , DNA/química , Humanos , DNA Catalítico/química , DNA Catalítico/metabolismo , Limite de Detecção , Ferrocianetos/químicaRESUMO
Subsequently to the publication of the above article, an interested reader drew to the authors' attention that, for the cell invasion and migration assay images shown for the A2780 cell line in Figs. 1 and Fig. 3 on p. 3433 and 3435 respectively, the same data panel had apparently been selected to show the results of the siNEAT1 experiment in Fig. 1 and the siTJP3 experiment in Fig. 3. After having reexamined their original data, the authors have realized that the image correctly shown for Fig. 1 was inadvertently copied across to Fig. 3. The corrected version of Fig. 3, now correctly showing the data for the siTJP3 experiment with the A2780 cell line, is shown on the next page. Note that this error did not significantly affect the results or the conclusions reported in this paper. All the authors agree to the publication of this Corrigendum, are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to correct this error, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 22: 34293439, 2020; DOI: 10.3892/mmr.2020.11428].
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Genotoxic therapy triggers reactive oxygen species (ROS) production and oxidative tissue injury. S-nitrosylation is a selective and reversible posttranslational modification of protein thiols by nitric oxide (NO), and 5,6,7,8-tetrahydrobiopterin (BH4) is an essential cofactor for NO synthesis. However, the mechanism by which BH4 affects protein S-nitrosylation and ROS generation has not been determined. Here, we showed that ionizing radiation disrupted the structural integrity of BH4 and downregulated GTP cyclohydrolase I (GCH1), which is the rate-limiting enzyme in BH4 biosynthesis, resulting in deficiency in overall protein S-nitrosylation. GCH1-mediated BH4 synthesis significantly reduced radiation-induced ROS production and fueled the global protein S-nitrosylation that was disrupted by radiation. Likewise, GCH1 overexpression or the administration of exogenous BH4 protected against radiation-induced oxidative injury in vitro and in vivo. Conditional pulmonary Gch1 knockout in mice (Gch1fl/fl; Sftpa1-Cre+/- mice) aggravated lung injury following irradiation, whereas Gch1 knock-in mice (Gch1lsl/lsl; Sftpa1-Cre+/- mice) exhibited attenuated radiation-induced pulmonary toxicity. Mechanistically, lactate dehydrogenase (LDHA) mediated ROS generation downstream of the BH4/NO axis, as determined by iodoacetyl tandem mass tag (iodoTMT)-based protein quantification. Notably, S-nitrosylation of LDHA at Cys163 and Cys293 was regulated by BH4 availability and could restrict ROS generation. The loss of S-nitrosylation in LDHA after irradiation increased radiosensitivity. Overall, the results of the present study showed that GCH1-mediated BH4 biosynthesis played a key role in the ROS cascade and radiosensitivity through LDHA S-nitrosylation, identifying novel therapeutic strategies for the treatment of radiation-induced lung injury.
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Biopterinas , GTP Cicloidrolase , Lesão Pulmonar , Espécies Reativas de Oxigênio , Animais , Biopterinas/análogos & derivados , Biopterinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Lesão Pulmonar/metabolismo , Lesão Pulmonar/etiologia , GTP Cicloidrolase/metabolismo , GTP Cicloidrolase/genética , Humanos , Tolerância a Radiação/genética , Lactato Desidrogenase 5/metabolismo , Camundongos Knockout , Óxido Nítrico/metabolismo , L-Lactato Desidrogenase/metabolismo , L-Lactato Desidrogenase/genética , Processamento de Proteína Pós-Traducional , Radiação IonizanteRESUMO
Quest for ultrathin and highly effective anticorrosion coating films is critical for both fundamental community of materials science and industrial economics. A two-dimensional hexagonal boron nitride (h-BN) film is a newly developed effective anticorrosion material due to its superior impermeability, thermal stability, and chemical stability. However, research in growth and anticorrosion properties of large-area dense h-BN coating films still lies in its infancy. Here, we report on the synthesis of a large-area and continuous dense few-layer (â¼4) h-BN coating film onto a metal surface by chemical vapor deposition (CVD) and its anticorrosion properties both in air and seawater environments. Cu coated in h-BN, which functions as an anticorrosive coating, exhibits an impressively reduced corrosion rate (CR) in a 3.5% NaCl solution (which mimics a seawater environment) when compared to bare Cu (approximately 27 times). At 200 °C, the h-BN coating can prevent Cu foil's surface from oxidizing, although doing so will cause a significant amount of oxide particles to simultaneously form on the bare Cu surface. In the meantime, the performance of the h-BN film remains unaltered after 100 days in an atmospheric environment, demonstrating the ultrahigh stability and corrosion resistance of the as-grown h-BN film.
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Background: Research on the risk factors for cervical cancer in Yunnan Province's four characteristic ethnic groups (Han, Bai, Dai, and Hani) is lacking. Objective: To study the risk factors of cervical cancer in four ethnic women in Yunnan Province, and to provide evidence for its prevention. Methods: The cervical cancer patients of Han, Bai, Dai and Hani ethnic groups in Yunnan Province who were first diagnosed in the Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center) from January 2011 to December 2020 were selected as the research objects. The 1:1 matched case-control study method was used, and single factor and conditional logistic regression were used for statistical analysis. Results: HPV types 16, 18 and 58 are mostly related with cervical cancer, the younger the age of the last pregnancy, the more times of pregnancy, childbirth and abortion, especially the younger the first marriage age of Bai and Dai, are the risk factors of cervical cancer; the infection of genital tract bacteria, mycoplasma and chlamydia is closely related to the incidence of cervical cancer in four ethnicities. Multifactorial analysis showed that demographic characteristics and environment/behavior were not included in the influencing factors of cervical cancer; among Han, Bai, Dai and Hani ethnic minorities, contraception (OR=0.29, OR=0.03, OR=0.09, OR=0.16, P<0.05) was positive factor, HPV infection (OR=64.77, OR=128.71, OR=71.89, OR=40.07, P<0.01) was a causative factor of cervical cancer. Conclusion: Risk of high parity with cervical cancer could be due to a complex interplay of factors, it is very important to formulate prevention strategies and measures in line with the cervical cancer of Han, Bai, Dai and Hani ethnic groups women in Yunnan Province.
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Neuronal ferroptosis has been found to contribute to degenerative brain disorders and traumatic and hemorrhagic brain injury, but whether radiation-induced brain injury (RIBI), a critical deleterious effect of cranial radiation therapy for primary and metastatic brain tumors, involves neuronal ferroptosis remains unclear. We have recently discovered that deletion of reprimo (RPRM), a tumor suppressor gene, ameliorates RIBI, in which its protective effect on neurons is one of the underlying mechanisms. In this study, we found that whole brain irradiation (WBI) induced ferroptosis in mouse brain, manifesting as alterations in mitochondrial morphology, iron accumulation, lipid peroxidation and a dramatic reduction in glutathione peroxidase 4 (GPX4) level. Moreover, the hippocampal ferroptosis induced by ionizing irradiation (IR) mainly happened in neurons. Intriguingly, RPRM deletion protected the brain and primary neurons against IR-induced ferroptosis. Mechanistically, RPRM deletion prevented iron accumulation by reversing the significant increase in the expression of iron storage protein ferritin heavy chain (Fth), ferritin light chain (Ftl) and iron importer transferrin receptor 1 (Tfr1), as well as enhancing the expression of iron exporter ferroportin (Fpn) after IR. RPRM deletion also inhibited lipid peroxidation by abolishing the reduction of GPX4 and stearoyl coenzyme A desaturase-1 (SCD1) induced by IR. Importantly, RPRM deletion restored or even increased the expression of nuclear factor, erythroid 2 like 2 (Nrf2) in irradiated neurons. On top of that, compromised cyclic AMP response element (CRE)-binding protein (CREB) signaling was found to be responsible for the down-regulation of Nrf2 and SCD1 after irradiation, specifically, RPRM bound to CREB and promoted its degradation after IR, leading to a reduction of CREB protein level, which in turn down-regulated Nrf2 and SCD1. Thus, RPRM deletion recovered Nrf2 and SCD1 through its impact on CREB. Taken together, neuronal ferroptosis is involved in RIBI, RPRM deletion prevents IR-induced neuronal ferroptosis through restoring CREB-Nrf2/SCD1 pathways.
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Lesões Encefálicas , Ferroptose , Lesões por Radiação , Animais , Camundongos , Apoferritinas , Encéfalo , Lesões Encefálicas/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Ferroptose/genética , Ferro , Fator 2 Relacionado a NF-E2/genéticaRESUMO
OBJECTIVE: Neuroendocrine carcinoma of the cervix (NECC) is extremely rare in clinical practice. This study aimed to methodologically analyze the clinicopathological factors associated with NECC patients and to develop a validated survival prediction model. METHODS: A total of 535 patients diagnosed with NECC between 2004 and 2016 were identified from the Surveillance, Epidemiology and End Results (SEER) database, while 122 patients diagnosed with NECC at Yunnan Cancer Hospital (YCH) from 2006 to 2019 were also recruited. Patients from the SEER database were divided into a training cohort (n = 376) and a validation cohort (n = 159) in a 7:3 ratio for the construction and internal validation of the nomogram. External validation was performed in a cohort at YCH. The Kaplan-Meier method was used for survival analysis, the Log-rank method test was used for univariate analysis of prognostic influences, and the Cox regression model was used for multivariate analysis. RESULTS: The 3-year and 5-year overall survival (OS) rates for patients with NECC in SEER were 43.6% and 39.7%, respectively. In the training cohort, multivariate analysis showed independent prognostic factors for NECC patients including race, tumor size, distant metastasis, stage, and chemotherapy (p<0.05). For extended application in other cohorts, a nomogram including four factors without race was subsequently created. The consistency index (C-index) of the nomogram predicting survival was 0.736, which was well-validated in the validation cohorts (0.746 for the internal validation cohort and 0.765 for the external validation cohort). In both the training and validation cohorts, the 3-year survival rates predicted by the nomogram were comparable to the actual ones. We then succeeded in dividing patients with NECC into high- and low-risk groups concerning OS using the nomogram we developed. Besides, univariate analysis showed that chemotherapy ≥4 cycles may improve the OS of patients at YCH with NECC. CONCLUSION: We successfully constructed a nomogram that precisely predicts the OS for patients with NECC based on the SEER database and a large single-center retrospective cohort. The visualized and practical model can distinguish high-risk patients for recurrence and death who may benefit from clinical trials of boost therapy effectively. We also found that patients who received more than 4 cycles of chemotherapy acquired survival benefits than those who received less than 4 cycles.
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Carcinoma Neuroendócrino , Neoplasias do Colo do Útero , Feminino , Humanos , Colo do Útero , Prognóstico , Estudos Retrospectivos , China/epidemiologia , Carcinoma Neuroendócrino/terapia , Neoplasias do Colo do Útero/terapiaRESUMO
BACKGROUND: Traditional Chinese medicine (TCM) has the advantage of low toxicity of natural ingredients, multiple targets and effects, and low medication costs. It has unique advantages for metabolic and chronic diseases. Huangqin-Huanglian decoction (HQHLD) is composed of Scutellariae Radix, Coptidis Rhizoma, Rehmanniae Radix, and Gentianae Radix Et Rhozima; it has great potential for the treatment of NAFLD with the modern pharmacological research and TCM theory, but there is still a relative lack of research on the potential targets and pharmacological effects of HQHLD. METHODS: In this work, we have used network pharmacology to predict the targets and signaling pathways of HQHLD, and validated NAFLD-related targets using the HFD model in order to explore more therapeutic drugs and methods for NAFLD. We collected the HQHLD ingredients and NAFLD targets through TCMSP, ETCM, DisGeNET, HGMD, MalaCards, OMIM, and TTD, built ingredients-target networks by Cytoscape, and screened key ingredients in HQHLD. DAVID and Metascape databases were used for GO functional enrichment analysis and KEGG pathway enrichment analysis, respectively. Molecular docking of the key ingredients and key targets was performed by AutoDock. We verified the effect of HQHLD on high-fat diet (HFD) mice by measuring the weight, liver weight index, and the level of TG, TC, LDL-C, and HDLC. HE staining and oil-red staining were performed to detect the damage and fat accumulation in the liver. The changes in INSR, PPAR-α, PPAR-γ, TNF-α, and caspase3 were experimented with WB. RESULTS: With the network pharmacology analysis, we found quercetin, baicalein, sitosterol, wogonin, oroxylin-A, glycyrrhizin, hydroberberine, berberine, sesamin, and carotene to be the main ingredients in HQHLD. According to KEGG pathway analysis, INSR, AKT, JNK1, PPAR-α, PPAR-γ, and the other 16 targets are the main targets of HQHLD in the treatment of NAFLD. We took HFD mice as the in vivo model of NAFLD. Our results showed that HQHLD could reduce liver weight, and TG and LDL-C levels, and increase HDL-C level in serum. By HE and oil red staining, we found that HQHLD could protect the morphology of hepatocytes and reduce fat in the liver. We also found HQHLD to protect the liver by increasing the expression of INSR and PPAR-α, and reducing the expression of PPAR-γ, TNF-α, and caspase3 in the liver. CONCLUSION: In conclusion, our study has firstly studied the main ingredients and key targets of HQHDL in treating NAFLD by network pharmacology analysis, and preliminarily confirmed that HQHLD could alleviate NAFLD in a multi-target way by lowering fatty acids, and decreasing insulin resistance, inflammation, and apoptosis in the liver.
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Medicamentos de Ervas Chinesas , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Scutellaria baicalensis , Dieta Hiperlipídica/efeitos adversos , LDL-Colesterol , Simulação de Acoplamento Molecular , Receptores Ativados por Proliferador de Peroxissomo , Fator de Necrose Tumoral alfaRESUMO
The relative research on investigating the association between dietary diversity scores and anthropometric status among young children is few and inconsistent. Since understanding this association is quite essential to give more detailed advice about diet to ensure young children's healthy growth, we sought to determine the association between dietary diversity levels and anthropometric status among young children under 24 months. The study included 1408 mother-child pairs from the Tongji Maternal and Child Health Cohort, whose children range in age from 12 to 24 months. Multivariable logistic regressions were used to examine the effect of dietary diversity on children's anthropometric failure and obesity. All obese children aged 12 and 24 months had low-medium diverse diets in their first year of life. Risks of anthropometric failure for 12-month young children consumed low-medium diverse diets in their first year and 24-month young children consumed low-medium diverse diets in their second year are, respectively, 1.27 (odds ratio [OR], 95% confidence interval [CI] = [1.06-1.53]) and 1.19 (OR, 95% CI = [1.02-1.40]) times of those who consumed high diverse diets in corresponding year. The risk of anthropometric failure for 24-month-old children who consumed low-medium diverse diets during their first year of life is 4.70 (OR, 95% CI = [1.62-19.91]) times that of young children who consumed highly diverse diets during their first year of life. Introducing more diverse diets to young children under 24 months of age may be an effective strategy to prevent anthropometric failure and obesity in young children in later life.
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Obesidade Infantil , Criança , Humanos , Lactente , Pré-Escolar , Obesidade Infantil/epidemiologia , Dieta , Antropometria , China/epidemiologia , Estado NutricionalRESUMO
CONTEXT: Evidence on the associations of low-carbohydrate diet (LCD) during pregnancy with gestational diabetes mellitus (GDM) has been limited and inconsistent. OBJECTIVE: We aimed to prospectively evaluate the risk of GDM associated with the LCD considering the quality of macronutrients. METHODS: All participants were from a prospective cohort in Wuhan, China. The overall, healthy LCD (emphasizing low-quality carbohydrates, plant protein, and unsaturated fat), and unhealthy LCD (emphasizing high-quality carbohydrates, animal protein, and saturated fat) scores were calculated according to the percentage of energy intake from carbohydrates, protein, and fat. GDM was screened by a 75-g oral glucose tolerance test between 24 and 28 weeks. Poisson regression models were used to calculate relative risks (RRs) and 95% CIs. RESULTS: Of 2337 pregnant women, 257 (11.0%) were diagnosed with GDM. Overall LCD score was not associated with risk of GDM, but the healthy and unhealthy LCD scores were associated with the risk of GDM. The multivariable-adjusted RRs (95% CI) were 0.68 (0.49-0.94) and 1.52 (1.11-2.08) for healthy and unhealthy LCD scores comparing the highest with the lowest quartile. Substituting high-quality carbohydrates for low-quality carbohydrates and animal protein, and substituting unsaturated fat for saturated fat, were associated with a 13% to 29% lower risk of GDM. CONCLUSION: A healthy LCD during pregnancy characterized by high-quality carbohydrates, plant protein, and unsaturated fat was associated with a lower risk of GDM, whereas an unhealthy LCD consisting of low-quality carbohydrates, animal protein, and saturated fat was associated with a higher risk of GDM.
Assuntos
Diabetes Gestacional , Animais , Gravidez , Feminino , Humanos , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/etiologia , Estudos Prospectivos , Dieta com Restrição de Carboidratos , Carboidratos , Ácidos Graxos , Gorduras Insaturadas , Proteínas de Plantas , Dieta , Fatores de RiscoRESUMO
SHP-1 (Src homology region 2 domain-containing phosphatase 1) is a well-known negative regulator of T cells, whereas its close homolog SHP-2 is the long-recognized main signaling mediator of the PD-1 inhibitory pathway. However, recent studies have challenged the requirement of SHP-2 in PD-1 signaling, and follow-up studies further questioned the alternative idea that SHP-1 may replace SHP-2 in its absence. In this study, we systematically investigate the role of SHP-1 alone or jointly with SHP-2 in CD8+ T cells in a series of gene knockout mice. We show that although SHP-1 negatively regulates CD8+ T cell effector function during acute lymphocytic choriomeningitis virus (LCMV) infection, it is dispensable for CD8+ T cell exhaustion during chronic LCMV infection. Moreover, in contrast to the mortality of PD-1 knockout mice upon chronic LCMV infection, mice double deficient for SHP-1 and SHP-2 in CD8+ T cells survived without immunopathology. Importantly, CD8+ T cells lacking both phosphatases still differentiate into exhausted cells and respond to PD-1 blockade. Finally, we found that SHP-1 and SHP-2 suppressed effector CD8+ T cell expansion at the early and late stages, respectively, during chronic LCMV infection.