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1.
Clin Cosmet Investig Dermatol ; 17: 565-571, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38482177

RESUMO

Alopecia Areata is a hair disorder influenced by factors such as genetics, immune system, and environmental triggers. The pathogenesis of this condition is still unclear, leading to unsatisfactory current treatments and causing a large number of patients to suffer from it. Janus kinase inhibitors are a new class of drugs that have emerged in recent years and are expected to be promising therapeutic tools for alopecia areata. We report five patients with varying backgrounds and severity of alopecia areata. All of them had received conventional therapy without success. Five patients took Upadacitinib at a dose of 15 mg once daily, and all of them achieved satisfactory efficacy. No adverse events were observed during the treatment of 5 patients.

2.
J Cosmet Dermatol ; 23(7): 2361-2367, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38551321

RESUMO

OBJECTIVE: Many studies have emphasized the possible role of probiotics in psoriasis, probiotic supplementation might be helpful to treat psoriasis. This study systematically evaluated the efficacy of probiotic supplementation for the treatment of psoriasis. METHODS: We searched some databases with keywords until November 10, 2023, including PubMed, Cochrane Library, Embase, and Web of Science. These keywords included probiotics, psoriasis RCT, and so on. After rigorous literature screening by two authors, five studies were identified. Eventually, the required data were independently extracted by another author. RESULTS: A total of five studies with 286 patients were included. The pooled results showed that the efficacy of probiotic supplementation was superior to placebo in the treatment of psoriasis. The Psoriasis Area and Severity Index (SMD = -1.40, 95% Cl = -2.63 to -0.17, p < 0.00001) and Dermatology Life Quality Index (SMD = -0.92, 95% Cl = -1.86 to 0.01, p < 0.00001). Score decreased after probiotic supplementation. CONCLUSIONS: The meta-analysis showed that probiotic supplementation could be a new treatment option for psoriasis.


Assuntos
Suplementos Nutricionais , Probióticos , Psoríase , Índice de Gravidade de Doença , Psoríase/terapia , Psoríase/tratamento farmacológico , Probióticos/administração & dosagem , Probióticos/uso terapêutico , Humanos , Resultado do Tratamento , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
J Ethnopharmacol ; 327: 118039, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38479545

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The anti-tumor related diseases of Coptidis Rhizoma (Huanglian) were correlated with its traditional use of removing damp-heat, clearing internal fire, and counteracting toxicity. In the recent years, Coptidis Rhizoma and its components have drawn extensive attention toward their anti-tumor related diseases. Besides, Coptidis Rhizoma is traditionally used as an anti-inflammatory herb. Epiberberine (EPI) is a significant alkaloid isolated from Coptidis Rhizoma, and exhibits multiple pharmacological activities including anti-inflammatory. However, the effect of epiberberine on breast cancer and the inflammatory factors of metastatic breast cancer-induced osteolysis has not been demonstrated clearly. AIM OF THE STUDY: Bone metastatic breast cancer can lead to osteolysis via inflammatory factors-induced osteoclast differentiation and function. In this study, we try to analyze the effect of epiberberine on breast cancer and the inflammatory factors of metastatic breast cancer-induced osteolysis. METHODS: To evaluate whether epiberberine could suppress bone metastatic breast cancer-induced osteolytic damage, healthy female Balb/c mice were intratibially injected with murine triple-negative breast cancer 4T1 cells. Then, we examined the inhibitory effect and underlying mechanism of epiberberine on breast cancer-induced osteoclastogenesis in vitro. Xenograft assay was used to study the effect of epiberberine on breast cancer cells in vivo. Moreover, we also studied the inhibitory effects and underlying mechanisms of epiberberine on RANKL-induced osteoclast differentiation and function in vitro. RESULTS: The results show that epiberberine displayed potential therapeutic effects on breast cancer-induced osteolytic damage. Besides, our results show that epiberberine inhibited breast cancer cells-induced osteoclast differentiation and function by inhibiting secreted inflammatory cytokines such as IL-8. Importantly, we found that epiberberine directly inhibited RANKL-induced differentiation and function of osteoclast without cytotoxicity. Mechanistically, epiberberine inhibited RANKL-induced osteoclastogensis via Akt/c-Fos signaling pathway. Furthermore, epiberberine combined with docetaxel effectively protected against bone loss induced by metastatic breast cancer cells. CONCLUSIONS: Our findings suggested that epiberberine may be a promising natural compound for treating bone metastatic breast cancer-induced osteolytic damage by inhibiting IL-8 and is worthy of further exploration in preclinical and clinical trials.


Assuntos
Berberina/análogos & derivados , Neoplasias Ósseas , Neoplasias da Mama , Medicamentos de Ervas Chinesas , Osteólise , Humanos , Feminino , Animais , Camundongos , Osteólise/tratamento farmacológico , Osteólise/metabolismo , Osteólise/patologia , Neoplasias da Mama/patologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/metabolismo , Interleucina-8/metabolismo , Osteoclastos , Osteogênese , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Anti-Inflamatórios/farmacologia , Ligante RANK/metabolismo
4.
Plant J ; 118(5): 1388-1399, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38407913

RESUMO

Pre-harvest sprouting (PHS) is a significant threat to global food security due to its association with losses in both yield and quality. Among the genes involved in PHS resistance in wheat, PHS-3D (TaMyb10-D) plays a crucial role. Here, we characterized the sequence variations of TaMyb10 genes in 416 bread wheat and 302 Aegilops tauschii accessions. Within TaMyb10-A sequences, we identified a deletion ranging from 214 to 305 bp in the signal and amino acid coding region, present in 61.3% of the accessions. Similarly, 79.3% of the TaMyb10-B sequences within the third exon region exhibited a 19 bp deletion. Additionally, 40.8% of the accessions lacked the 2.4 Mb fragment (in/del mutations) on Chr3D, where TaMyb10-D/PHS-3D was located. Interestingly, the geographical distribution of accessions showed little correlation with the divergence of TaMyb10. TaMyb10-A-IIIDele, TaMyb10-B-IVDele, and TaMyb10-D-VDele genotypes were prevalent in wheat populations across continents. Despite their structural variations, the five distinct protein types exhibited comparable ability to bind the promoters of downstream genes in the flavonoid and ABA pathways, such as CHS, DFR, and NCED. Furthermore, the combination of TaMyb10 homologs was significantly associated with grain color and germination percentages. Accessions exclusively harboring TaMyb10-D displayed red seed color and reduced germination percentages, indicating the predominant role of TaMyb10-D compared to TaMyb10-A and TaMyb10-B. This comprehensive investigation enhances our understanding of the structural variations and functional divergence of TaMyb10, providing valuable insights and resources for improving PHS resistance in wheat.


Assuntos
Proteínas de Plantas , Triticum , Triticum/genética , Triticum/fisiologia , Triticum/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Grão Comestível/genética , Grão Comestível/crescimento & desenvolvimento , Aegilops/genética , Germinação/genética , Variação Genética , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/fisiologia
5.
Gynecol Oncol ; 178: 8-13, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37734188

RESUMO

BACKGROUND: We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age. METHODS: According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up. RESULTS: The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple+ infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found. CONCLUSION: This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11.


Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Idoso , Adulto , Papillomavirus Humano , Estudos de Coortes , Estudos Prospectivos , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Infecções por Papillomavirus/tratamento farmacológico , Papillomaviridae , Genótipo
6.
Nat Mater ; 22(7): 853-859, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37349395

RESUMO

III-nitride wide bandgap semiconductors are promising materials for modern optoelectronics and electronics. Their application has progressed greatly thanks to the continuous quality improvements of heteroepitaxial films grown on large-lattice-mismatched foreign substrates. But compared with bulk single crystals, there is still tremendous room for the further improvement of the material quality. Here we show a paradigm to achieve high-quality III-nitride heteroepitaxial films by the controllable discretization and coalescence of columns. By adopting nano-patterned AlN/sapphire templates with regular hexagonal holes, discrete AlN columns coalesce with uniform out-of-plane and in-plane orientations guaranteed by sapphire nitridation pretreatment and the ordered lateral growth of cleavage facets, which efficiently suppresses the regeneration of threading dislocations during coalescence. The density of dislocation etch pits in the AlN heteroepitaxial film reaches 3.3 × 104 cm-2, close to the present available AlN bulk single crystals. This study facilitates the growth of bulk-class quality III-nitride films featuring low cost and scalability.


Assuntos
Óxido de Alumínio , Eletrônica , Semicondutores , Software
7.
Environ Pollut ; 331(Pt 1): 121755, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37142207

RESUMO

Adverse male reproduction caused by phthalate ester (PAE) exposure has been well documented in vivo. However, existing evidence from population studies remains inadequate to demonstrate the impact of PAE exposure on spermatogenesis and underlying mechanisms. Our present study aimed to explore the potential link between PAE exposure and sperm quality and the possible mediation by sperm mitochondrial and telomere in healthy male adults recruited from the Hubei Province Human Sperm Bank, China. Nine PAEs were determined in one pooled urine sample prepared from multiple collections during the spermatogenesis period from the same participant. Sperm telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) were determined in sperm samples. The sperm concentration and count per quartile increment in mixture concentrations were -4.10 million/mL (-7.12, -1.08) and -13.52% (-21.62%, -4.59%), respectively. We found one quartile increase in PAE mixture concentrations to be marginally associated with sperm mtDNAcn (ß = 0.09, 95% CI: -0.01, 0.19). Mediation analysis showed that sperm mtDNAcn significantly explained 24.6% and 32.5% of the relationships of mono-2-ethylhexyl phthalate (MEHP) with sperm concentration and sperm count (ß = -0.44 million/mL, 95% CI: -0.82, -0.08; ß = -1.35, 95% CI: -2.54, -0.26, respectively). Our study provided a novel insight into the mixed effect of PAEs on adverse semen quality and the potential mediation role of sperm mtDNAcn.


Assuntos
Ácidos Ftálicos , Análise do Sêmen , Humanos , Masculino , Adulto , Sêmen , População do Leste Asiático , Exposição Ambiental/análise , Espermatozoides , Ácidos Ftálicos/urina , DNA Mitocondrial , China
8.
Connect Tissue Res ; 64(4): 376-388, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37092609

RESUMO

The widespread prevalence of Pelvic Organ Prolapse (POP) and the paucity of ongoing treatments prompted us to develop a unique rat model combining ovariectomy and simulated vaginal delivery. We hypothesized that the tissue changes caused by low hormone levels and mechanical stretch could complement each other. Thus, the combined model can potentially mimic the collagen metabolism of vaginal wall tissue as well as mechanical stretch properties to complement disease progression in POP. Ovariectomy with sequential simulated vaginal delivery was performed on rats in the modeling group. Sham surgeries were performed as control. At 2, 4, and 12 weeks after modeling, the vaginal tissues of rats were evaluated by Masson's trichrome staining, Picro-Sirius red staining, immunohistochemistry, western blotting, and uniaxial tensile tests. Compared to the control group, the vaginal tissues of the model rats showed an atrophic epithelial layer and loose collagen fibers. The smooth muscle fibers were ruptured, smaller in diameter, and disorganized. The ratio of collagen type I/III significantly increased, but the contents of both Collagen I and III decreased. The expression of metalloproteinases 2 and 9 in the tissues increased, and the expression of tissue inhibitors of metalloproteinases 1 and 2 decreased. The tangent modulus of the tissues was significantly increased in the model rats. We verified a novel method to establish a pelvic organ prolapse model in rats. This approach combined the advantages of low hormone levels and mechanical stretch effects.


Assuntos
Prolapso de Órgão Pélvico , Feminino , Humanos , Ratos , Animais , Prolapso de Órgão Pélvico/metabolismo , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Ovariectomia , Hormônios
9.
Ecotoxicol Environ Saf ; 256: 114872, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37027942

RESUMO

Manganese (Mn), as one of the environmental risk factors for Parkinson's disease (PD), has been widely studied. Though autophagy dysfunction and neuroinflammation mainly are responsible for the causative issue of Mn neurotoxicity, the molecular mechanism of parkinsonism caused by Mn has not been explored clearly. The results of in vivo and in vitro experiments showed that overexposure to Mn caused neuroinflammation impairment and autophagy dysfunction, accompanied by the increase of IL-1ß, IL-6, and TNF-α mRNA expression, and nerve cell apoptosis, microglia cell activation, NF-κB activation, poor neurobehavior performance. This is due to Mn-induced the downregulation of SIRT1. Upregulation of SIRT1 in vivo and in vitro could alleviate Mn-induced autophagy dysfunction and neuroinflammation, yet these beneficial effects were abolished following 3-MA administration. Furthermore, we found that Mn interfered with the acetylation of FOXO3 by SIRT1 in BV2 cells, leading to a decrease in the nuclear translocation of FOXO3, and its binding of LC3B promoter and transcription activity. This could be antagonized by the upregulation of SIRT1. Finally, it is proved that SIRT1/FOXO3-LC3B autophagy signaling involves in Mn-induced neuroinflammation impairment.


Assuntos
Manganês , Doenças Neuroinflamatórias , Autofagia , Proteína Forkhead Box O3/metabolismo , Manganês/metabolismo , Microglia , Sirtuína 1/metabolismo , Animais , Camundongos
10.
Cell Rep ; 42(1): 111972, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36641751

RESUMO

KRAS is widely mutated in human cancers, resulting in unchecked tumor proliferation and metastasis, which makes identifying KRAS-targeting therapies a priority. Herein, we observe that mutant KRAS specifically promotes the formation of the ERK2-p53 complex in stomach/colorectal tumor cells. Disruption of this complex by applying MEK1/2 and ERK2 inhibitors elicits strong apoptotic responses in a p53-dependent manner, validated by genome-wide knockout screening. Mechanistically, p53 physically associates with phosphorylated ERK2 through a hydrophobic interaction in the presence of mutant KRAS, which suppresses p53 activation by preventing the recruitment of p300/CBP; trametinib disrupts the ERK2-p53 complex by reducing ERK2 phosphorylation, allowing the acetylation of p53 protein by recruiting p300/CBP; acetylated p53 activates PUMA transcription and thereby kills KRAS-mutant tumors. Our study shows an important role for the ERK2-p53 complex and provides a potential therapeutic strategy for treating KRAS-mutant cancer.


Assuntos
Neoplasias Colorretais , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Fosforilação , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Estômago
11.
EMBO Mol Med ; 15(3): e16235, 2023 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-36652375

RESUMO

Poly-ADP-ribose polymerase (PARP) inhibitors (PARPi) have shown great promise for treating BRCA-deficient tumors. However, over 40% of BRCA-deficient patients fail to respond to PARPi. Here, we report that thioparib, a next-generation PARPi with high affinity against multiple PARPs, including PARP1, PARP2, and PARP7, displays high antitumor activities against PARPi-sensitive and -resistant cells with homologous recombination (HR) deficiency both in vitro and in vivo. Thioparib treatment elicited PARP1-dependent DNA damage and replication stress, causing S-phase arrest and apoptosis. Conversely, thioparib strongly inhibited HR-mediated DNA repair while increasing RAD51 foci formation. Notably, the on-target inhibition of PARP7 by thioparib-activated STING/TBK1-dependent phosphorylation of STAT1, triggered a strong induction of type I interferons (IFNs), and resulted in tumor growth retardation in an immunocompetent mouse model. However, the inhibitory effect of thioparib on tumor growth was more pronounced in PARP1 knockout mice, suggesting that a specific PARP7 inhibitor, rather than a pan inhibitor such as thioparib, would be more relevant for clinical applications. Finally, genome-scale CRISPR screening identified PARP1 and MCRS1 as genes capable of modulating thioparib sensitivity. Taken together, thioparib, a next-generation PARPi acting on both DNA damage response and antitumor immunity, serves as a therapeutic potential for treating hyperactive HR tumors, including those resistant to earlier-generation PARPi.


Assuntos
Interferon Tipo I , Neoplasias , Animais , Camundongos , Linhagem Celular Tumoral , Reparo do DNA , Recombinação Homóloga , Interferon Tipo I/genética , Interferon Tipo I/uso terapêutico , Neoplasias/genética , Ftalazinas/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Reparo de DNA por Recombinação , Proteínas de Ligação a RNA/genética , Resistencia a Medicamentos Antineoplásicos
12.
Chin Med Sci J ; 37(2): 91-94, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35796333

RESUMO

Considering the limitations of medical science and the risks associated with medical treatments, we need to re-examine the connotation of medical science from the perspective of philosophy. Medical science is the natural expression of human kindness and human nature of rescuing the dying and healing the wounded. It is a combination of the natural sciences, social sciences, and humanities. From the perspectives of medical philosophy and humanistic care, this article expounds the concepts and ideas of evidence-based, translational, and precision medicine in modern medicine and emphasizes the importance of avoiding new technical bureaucracy, paying attention to achieving a holistic view and systematic understanding, and avoiding biases in development because of the loss of the humanistic spirit in modern medical practice.


Assuntos
Medicina , Ciências Humanas , Humanos , Medicina/tendências , Filosofia Médica
13.
Neurochem Res ; 47(11): 3414-3427, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35871432

RESUMO

Overexposure to manganese (Mn) can induce cognitive deficits, but the underlying mechanisms are unclear. Microglial dysfunction and autophagic dysfunction have been implicated in Mn neurotoxicity. The neuroprotective effects of resveratrol (RSV) have been studied extensively, but the potential protective effects of RSV against Mn-induced cognitive dysfunction have not been evaluated. We investigated the effects of RSV on Mn-induced changes in PGC-1α, microglial M1/M2 polarization, and autophagy in vivo and in vitro. Kunming mice were treated with saline, MnCl2, RSV, or MnCl2 + RSV. The results showed that RSV improved cognitive dysfunction, suppressed release of inflammatory cytokines, promoted M2 microglial polarization, and increased autophagy in the hippocampi of Mn-treated mice. Furthermore, we also showed that Mn treatment significantly decreased the expression of PGC-1α, ULK1, BDNF, and activated NF-κB signaling. These effects were reversed by RSV pretreatment. In addition, RSV inhibited STAT6 acetylation, but did not affect ULK1 acetylation. Knockdown of PGC-1α using LV-PGC-1α shRNA reversed RSV-induced increases in the expression levels of PGC-1α, ULK1, LC3-II, and mitigated the RSV-induced decrease in the expression level of p62, in Mn-treated BV2 cells. Resveratrol-induced M2 polarization and autophagic flux were abolished by LV-PGC-1α shRNA pretreatment. These results showed that RSV exerted neuroprotective effects against Mn-induced learning and memory impairment partially through PGC-1α-mediated microglial M1/M2 polarization and autophagy.


Assuntos
Microglia , Fármacos Neuroprotetores , Animais , Autofagia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Citocinas/metabolismo , Manganês/metabolismo , Camundongos , Microglia/metabolismo , NF-kappa B/metabolismo , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , RNA Interferente Pequeno/farmacologia , Resveratrol/metabolismo , Resveratrol/farmacologia
14.
Environ Sci Pollut Res Int ; 29(46): 70125-70134, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35581467

RESUMO

Parabens are widely used as preservatives, which have been found to affect thyroid function in toxicological studies. However, population studies on whether they are associated with thyroid tumors remain unclear. This study aims to investigate the relationship between environmental paraben exposure and thyroid cancer and benign nodules. We recruited participants from the Department of Thyroid and Breast Surgery at Wuhan Central Hospital, Wuhan, China. The detectable percentages of methyl paraben, ethyl paraben, and propyl paraben in the urinary samples of 425 study subjects were 99.1%, 95.3%, and 92.0%, respectively. All uncorrected and creatinine-corrected parabens were moderately correlated with one another. After adjusting for possible confounders, all three parabens were associated with an increased risk of thyroid cancer. Furthermore, the mixture pollutant analysis of parabens found positive associations with risk of thyroid cancer (OR = 0.24, 95% CI: 0.18, 0.31) and benign nodules (OR = 1.33, 95% CI: 0.86, 1.80). We observed that individual exposure to paraben mixtures may be associated with the risk of thyroid cancer and benign nodules.


Assuntos
Poluentes Ambientais , Neoplasias da Glândula Tireoide , Adulto , Creatinina/análise , Exposição Ambiental/análise , Poluentes Ambientais/análise , Humanos , Parabenos/análise , Neoplasias da Glândula Tireoide/induzido quimicamente , Neoplasias da Glândula Tireoide/epidemiologia
15.
Light Sci Appl ; 11(1): 71, 2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35322013

RESUMO

Solving the doping asymmetry issue in wide-gap semiconductors is a key difficulty and long-standing challenge for device applications. Here, a desorption-tailoring strategy is proposed to juggle the carrier concentration and transport. Specific to the p-doping issue in Al-rich AlGaN, self-assembled p-AlGaN superlattices with an average Al composition of over 50% are prepared by adopting this approach. The hole concentration as high as 8.1 × 1018 cm-3 is thus realized at room temperature, which is attributed to the significant reduction of effective Mg activation energy to 17.5 meV through modulating the activating path, as well as the highlighted Mg surface-incorporation by an intentional interruption for desorption. More importantly, benefiting from the constant ultrathin barrier thickness of only three monolayers via this approach, vertical miniband transport of holes is verified in the p-AlGaN superlattices, greatly satisfying the demand of hole injection in device application. 280 nm deep-ultraviolet light-emitting diodes are then fabricated as a demo with the desorption-tailored Al-rich p-AlGaN superlattices, which exhibit a great improvement of the carrier injection efficiency and light extraction efficiency, thus leading to a 55.7% increase of the light output power. This study provides a solution for p-type doping of Al-rich AlGaN, and also sheds light on solving the doping asymmetry issue in general for wide-gap semiconductors.

16.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(1): 17-23, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35300760

RESUMO

Objective To investigate the clinical characteristics of preadolescent and adolescent female patients with ovarian mass combined with dysplasia of secondary sexual characteristics. Methods This study retrospectively analyzed 18 cases of ovarian mass combined with dysplasia of secondary sexual characteristics aged 0-19 years admitted to Peking Union Medical College Hospital from January 2012 to November 2019.By analyzing the clinical manifestations,surgical methods,postoperative pathology,therapies and prognosis of the cases,we summarized the diagnosis and treatment ideas. Results Among the 18 cases,7(7/18,38.9%)developed secondary sex signs before puberty,including 5 cases showing precocity(including 2 cases of juvenile granulosa cell tumor,1 case of gonadoblastoma,1 case of ovarian follicular cyst,and 1 case of 46,XY simple gonadal dysplasia combined with dysgerminoma)and 2 cases presenting masculine manifestations(1 case of steroid cell tumor and 1 case of sclerosing stromal tumor).The rest 11(11/18,61.1%)cases showed abnormal development of secondary sexual characteristics during puberty,including 8 cases with masculine manifestations or abnormal menstruation after menarche(7 cases with sex cord stromal cell tumor and 1 case with cystic granulosa cell tumor),2 cases with primary amenorrhea(1 case with androgen insensitivity syndrome combined with testicular sertoli cell tumor and 1 case with endometriosis cyst combined with reproductive tract malformation),and 1 case diagnosed as 46,XX gonadal dysplasia with serous cystadenoma and no secondary sexual development during puberty. Conclusions Sex hormone levels should be actively tested in the case of prepubertal secondary sexual characteristics appearing early,pubertal secondary sexual characteristics being abnormal(underdevelopment),and/or menstrual abnormalities.Imaging examination should be performed to exclude ovarian organic lesions,and chromosome karyotype analysis should be performed if necessary.The diagnosis of ovarian mass in preadolescent and adolescent females with related symptoms should first be alerted to cord stromal cell tumor.It is recommended to rule out the possibility of combined reproductive tract malformation in the adolescent patients with primary amenorrhea.Chromosome examination should be conducted to rule out the possibility of gonadal dysplasia in the adolescent patients with primary amenorrhea and/or no development of secondary sexual characteristics.


Assuntos
Neoplasias Ovarianas , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Hiperplasia/complicações , Lactente , Recém-Nascido , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Adulto Jovem
17.
Environ Pollut ; 300: 118969, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35157934

RESUMO

Earlier studies have suggested that exposure to phthalates (PAEs) may induce spermatozoa apoptosis. Sperm protamine as a molecular biomarker during spermatozoa apoptotic processes may mediate the association between PAE exposure and spermatozoa apoptosis. This study aimed to explore whether sperm protamine mediates the association of PAE exposure with spermatozoa apoptosis. We determined sperm protamine levels, 8 PAE metabolite concentrations in seminal plasma, and 3 spermatozoa apoptosis parameters among 111 men from an infertility clinic. The associations of PAEs as individual chemicals and mixtures with sperm protamine were determined. The mediating roles of protamine in the associations between PAEs and spermatozoa apoptosis parameters were examined by mediation analysis. After adjusting for confounders, we observed positive correlations between seminal plasma concentrations of mono(2-ethylhexyl) phthalate (MEHP) and sperm protamine-1 and protamine ratio. Estimates comparing highest vs. lowest quartiles of MEHP concentration were 4.65% (95% CI: 1.47%, 7.82%) for protamine-1 and 25.86% (95% CI: 3.05%, 53.73%) for protamine ratio. The quantile g-computation models showed that the adjusted protamine-1 per quartile increase in PAE mixture was 9.42% (95% CI: 1.00, 20.92) with MEHP being the major contributor. Although the joint association between PAE mixture and protamine ratio was negligible, MEHP was still identified as the main contributor. Furthermore, we found that protamine-2 and protamine ratio levels in the highest quartiles exhibited a decrease of 43.45% (95% CI: 60.54%, -19.75%) and an increase of 122.55% (95% CI: 60.00%, 209.57%) in Annexin V+/PI- spermatozoa relative to the lowest quartiles, respectively. Mediation analysis revealed that protamine ratio significantly mediated 55.6% of the association between MEHP and Annexin V+/PI- spermatozoa elevation (5.13%; 95% CI: 0.04%, 10.52%). Our findings provided evidence that human exposure to PAEs was associated with increased protamine levels which may mediate the process of spermatozoa apoptosis.


Assuntos
Análise de Mediação , Ácidos Ftálicos , Apoptose , Humanos , Masculino , Ácidos Ftálicos/análise , Protaminas/metabolismo , Espermatozoides/metabolismo
18.
BMC Nephrol ; 22(1): 305, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496793

RESUMO

BACKGROUND: Albumin is the primary body protein, which can predict the poor prognosis of several critical diseases. However, there are a few scientific studies on the relationship between albumin and the prognosis of dialysis patients. This study aims to explore the impact of hypoalbuminemia on the prognosis of critically ill patients with acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT). METHODS: This was a secondary study. Clinical, biochemical, and 28-day and 90-day mortality rates for critical patients with AKI who received CRRT between 2009 and 2016 were searched from the database to determine the effect of hypoalbuminemia on poor outcomes by univariate, multivariate, smooth curve fitting, and subgroup analysis. RESULTS: A total of 837 participants were enrolled in this study. Multivariate Cox proportional hazard regression analysis showed that hypoalbuminemia was associated with both 28-day and 90-day mortality risks after full adjustment for confounding variables, with an adjusted hazard ratio (95% confidence interval) of 0.63 (0.50-0.80) and 0.63 (0.51-0.78), respectively for each 1 g/dL increase of albumin. Stratified analysis showed that hypoalbuminemia was not associated with poor prognosis in oliguria. CONCLUSION: Hypoalbuminemia is associated with poor prognosis in critically ill AKI patients with CRRT; therefore, measuring albumin may be helpful for predicting the prognosis. However, in those with oliguria, this conclusion is not valid.


Assuntos
Injúria Renal Aguda/terapia , Estado Terminal/terapia , Terapia de Substituição Renal , Albumina Sérica/deficiência , Injúria Renal Aguda/sangue , Injúria Renal Aguda/mortalidade , Idoso , Análise de Variância , Estado Terminal/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Albumina Sérica/análise
19.
Front Oncol ; 11: 690275, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34222018

RESUMO

Cervical cancer is the fourth most common cancer worldwide, but its incidence varies greatly in different countries. Regardless of incidence or mortality, the burden of cervical cancer in China accounts for approximately 18% of the global burden. The Chinese Cervical Cancer Clinical Study is a hospital-based multicenter open cohort. The major aims of this study include (i) to explore the associations of therapeutic strategies with complications as well as mid- and long-term clinical outcomes; (ii) to widely assess the factors which may have an influence on the prognosis of cervical cancer and then guide the treatment options, and to estimate prognosis using a prediction model for precise post-treatment care and follow-up; (iii) to develop a knowledge base of cervical clinical auxiliary diagnosis and prognosis prediction using artificial intelligence and machine learning approaches; and (iv) to roughly map the burden of cervical cancer in different districts and monitoring the trend in incidence of cervical cancer to potentially inform prevention and control strategies. Patients eligible for inclusion were those diagnosed with cervical cancer, whether during an outpatient visit or hospital admission, at 47 different types of medical institutions in 19 cities of 11 provinces across mainland China between 2004 and 2018. In a total, 63 926 patients with cervical cancer were enrolled in the cohort. Since the project inception, a large number of standardized variables have been collected, including epidemiological characteristics, cervical cancer-related symptoms, physical examination results, laboratory testing results, imaging reports, tumor biomarkers, tumor staging, tumor characteristics, comorbidities, co-infections, treatment and short-term complications. Follow-up was performed at least once every 6 months within the first 5 years after receiving treatment and then annually thereafter. At present, we are developing a cervical cancer imaging database containing Dicom files with data of computed tomography/magnetic resonance imaging examination. Additionally, we are also collecting original pathological specimens of patients with cervical cancer. Potential collaborators are welcomed to contact the corresponding authors, and anyone can submit at least one specific study proposal describing the background, objectives and methods of the study.

20.
Int Urogynecol J ; 32(8): 2149-2157, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34165615

RESUMO

INTRODUCTION AND HYPOTHESIS: This study aimed to investigate the evaluation and management of complications after pelvic floor reconstructive surgery for pelvic organ prolapse in China. METHODS: Complications of pelvic floor reconstructive surgery for pelvic organ prolapses from 27 institutions were reported from November 2017 to October 2019. All complications were coded according to the category-time-site system proposed by the International Urogynecological Association (IUGA) and the International Continence Society (ICS). The severity of the complications was graded by the Clavien-Dindo grading system. Four scales were used to evaluate patient satisfaction and quality of life after management of the complications: the Patient Global Impression of Improvement (PGI-I), the Pelvic Floor Impact Questionnaire Short Form (PFIQ-7), the Pelvic Organ Prolapse Symptom Score (POP-SS), and a 5-point Likert-type scale that evaluated the patient's choice of surgery. RESULTS: Totally, 256 cases were reported. The occurrence of complications related to transvaginal mesh (TVM) and laparoscopic sacrocolpopexy (LSC) had a significantly longer post-surgery delay than those of native tissue repair surgery (p < 0.001 and p = 0.010, respectively). Both PFIQ-7 and POP-SS score were lower after management of complications (p < 0.001). Most respondents (81.67%) selected very much better, much better, or a little better on the PGI-I scale. Only 13.3% respondents selected unlikely or highly unlikely on the 5-point Likert-type scale. CONCLUSIONS: The occurrence of complications related to TVM surgery and LSC had a longer post-surgery delay than native tissue repair surgery. Long-term regular follow-up was vital in complication management. Patient satisfaction with the management of TVM complications was acceptable.


Assuntos
Prolapso de Órgão Pélvico , Procedimentos de Cirurgia Plástica , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Humanos , Prolapso de Órgão Pélvico/cirurgia , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Procedimentos de Cirurgia Plástica/efeitos adversos , Estudos Retrospectivos , Telas Cirúrgicas/efeitos adversos , Inquéritos e Questionários , Resultado do Tratamento
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