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1.
Zhonghua Fu Chan Ke Za Zhi ; 58(11): 818-825, 2023 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-37981767

RESUMO

Objective: To investigate the clinical characteristics, diagnosis, treatment, outcomes and prognostic factors of abdominal wall endometriosis (AWE). Methods: A total of 265 AWE patients who underwent surgical treatment in The First Affiliated Hospital of Anhui Medical University from January 2010 to April 2023 were retrospectively selected, and 244 patients had complete follow-up data. According to different depth of lesions, the enrolled patients were divided into three types: type Ⅰ (subcutaneous fat layer, n=30), type Ⅱ (anterior sheath muscle layer, n=174) and type Ⅲ (peritoneum layer, n=40). The general clinical features, perioperative conditions, recurrent outcome and prognostic factors were analyzed in three types. Results: (1) Compared with type Ⅲ patients, the age of onset, parity and incidence of pelvic endometriosis were significantly decreased in type Ⅱ patients [(32.0±4.0) vs (30.0±4.6) years, 1.6±0.6 vs 1.4±0.5, 10.0% (4/40) vs 1.7% (3/174), respectively; all P<0.05], while the proportion of patients with transverse incision was significantly increased [37.5% (15/40) vs 67.3% (115/171); P<0.01]. The first symptoms of type Ⅰ and type Ⅱ were mainly palpable mass in the abdominal wall [73.3% (22/30), 63.2% (110/174), respectively], but the first symptom of type Ⅲ was pain in the abdominal wall [55.0% (22/40); all P<0.05]. (2) No matter the results of preoperative B-ultrasound or intraoperative exploration, the lesion diameters of type Ⅰ, type Ⅱ and type Ⅲ showed significant upward trends (all P<0.05). The proportions of lesion diameter≥3 cm in type Ⅱ and type Ⅲ [67.8% (118/174), 80.0% (32/40)] were significantly higher than that in type Ⅰ (all P<0.05). The median operation time and blood loss of type Ⅰ and Ⅱ were significantly lower than those of type Ⅲ (type Ⅰ vs type Ⅲ: 37.5 vs 50.0 minutes, 10 vs 20 ml, all P<0.05; type Ⅱ vs type Ⅲ: 35.0 vs 50.0 minutes, 10 vs 20 ml, all P<0.05). (3) The median follow-up time was 49 months, the overall symptom remission rate was 98.4% (240/244), and the recurrence rate was 7.0% (17/244). There were no significant differences in recurrence rate and recurrence free time among three types (all P>0.05). Multivariate regression analysis showed that the depth, number, diameter of lesions and postoperative adjuvant medication were not significant factors for postoperative recurrence (all P>0.05). Conclusions: The clinical manifestations of type Ⅲ are the most serious, including obvious abdominal pain symptoms, larger lesion diameter, prolonged operation time, increased intraoperative blood loss and increased incidence of pelvic endometriosis. Complete resection of lesions is an effective treatment for AWE, with high symptom remission rate and low recurrence rate. The depth, number, diameter of lesions and postoperative adjuvant medication are not risk factors for recurrence.


Assuntos
Parede Abdominal , Endometriose , Gravidez , Feminino , Humanos , Adulto , Endometriose/diagnóstico , Endometriose/epidemiologia , Endometriose/cirurgia , Estudos Retrospectivos , Parede Abdominal/cirurgia , Parede Abdominal/patologia , Fatores de Risco , Dor Abdominal
2.
Proc Natl Acad Sci U S A ; 120(43): e2306475120, 2023 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-37847733

RESUMO

Anxiety disorders are a major public health concern and current treatments are inadequate for many individuals. Anxiety is more common in women than men and this difference arises during puberty. Sex differences in physiological stress responses may contribute to this variability. During puberty, gonadal hormones shape brain structure and function, but the extent to which these changes affect stress sensitivity is unknown. We examined how pubertal androgens shape behavioral and neural responses to social stress in California mice (Peromyscus californicus), a model species for studying sex differences in stress responses. In adults, social defeat reduces social approach and increases social vigilance in females but not males. We show this sex difference is absent in juveniles, and that prepubertal castration sensitizes adult males to social defeat. Adult gonadectomy does not alter behavioral responses to defeat, indicating that gonadal hormones act during puberty to program behavioral responses to stress in adulthood. Calcium imaging in the medioventral bed nucleus of the stria terminalis (BNST) showed that social threats increased neural activity and that prepubertal castration generalized these responses to less threatening social contexts. These results support recent hypotheses that the BNST responds to immediate threats. Prepubertal treatment with the nonaromatizable androgen dihydrotestosterone acts in males and females to reduce the effects of defeat on social approach and vigilance in adults. These data indicate that activation of androgen receptors during puberty is critical for programming behavioral responses to stress in adulthood.


Assuntos
Núcleos Septais , Diferenciação Sexual , Adulto , Humanos , Masculino , Feminino , Androgênios/farmacologia , Hormônios Gonadais/farmacologia , Hormônios Gonadais/fisiologia , Puberdade
3.
Beijing Da Xue Xue Bao Yi Xue Ban ; 55(4): 716-720, 2023 Aug 18.
Artigo em Chinês | MEDLINE | ID: mdl-37534657

RESUMO

OBJECTIVE: To compare the clinical effects of periodontal endoscopy aiding subgingival debridement with periodontal flap surgery on residual deep pockets of chronic periodontitis. METHODS: In the single-blind randomized control clinical study, residual deep pockets of periodontitis patients were still existing when re-evaluation after receiving initial periodontal treatment.The pockets which were necessary for bone surgery or guided tissue regeneration surgery were excluded.The sites were divided into test group and control group randomly.Test group sites underwent periodontal endoscopy aiding debridement and control group sites had periodontal flap surgery.At the baseline and 3 months later, parameters, such as plaque index (PLI), bleeding index (BI), probing depth (PD), attachment loss (AL) were examined.Bone height was measured by parallelly digital X-ray dental film.Meanwhile, treatment time and comfort scale (visual analogue scale, VAS) were also recorded. RESULTS: At baseline, 41 proximal sites with residual deep pockets were enrolled (test sites=21, control sites=20).All the parameters were not significantly different between the two groups.PD decreased by (1.67±0.91) mm from (5.62±0.86) mm to (3.95±0.74) mm in test group and by (2.25±1.12) mm from (5.95±1.19) mm to (3.70±0.73) mm in control group significantly (P < 0.05).The difference between the two groups was not significant.The PD of all the sites decreased lower than 5 mm, meanwhile, 76% was lower than 4 mm in test group and 85% was lower than 4 mm in control group.The BI decreased by 0.81±0.93 in test group and 0.65±0.99 in control group significantly (P < 0.05).The difference between the two groups was not significant.The PLI showed a tendency of decrease more in test group and bone height showed a trend of decrease more in control group, however, the difference was not significant.The treatment time was almost the same.The patients felt more comfortable in the test group (VAS was 0.60±0.89) than the control group (VAS was 1.20±1.64), however, the difference was not significant. CONCLUSION: Periodontal endoscopy aiding subgingival debridement could improve periodontal status by reducing the PD and BI significantly in short term.The effect was almost the same with periodontal surgery and endoscopy treatment may decrease the necessity of surgery.Meanwhile, periodontal endoscopy has more comfortable treatment experience than flap surgery and does not need extra treatment time.


Assuntos
Periodontite Crônica , Humanos , Desbridamento , Método Simples-Cego , Resultado do Tratamento , Periodontite Crônica/cirurgia , Endoscopia , Raspagem Dentária
4.
Zhonghua Yan Ke Za Zhi ; 59(9): 702-708, 2023 Sep 11.
Artigo em Chinês | MEDLINE | ID: mdl-36822593

RESUMO

Objective: To compare the efficacy and safety of trabeculotome tunnelling trabeculoplasty and gonioscopy-assisted transluminal trabeculotomy (GATT) in the treatment of open-angle glaucoma. Methods: A prospective randomized controlled study. The patients with open-angle glaucoma diagnosed in the ophthalmology center of Beijing Tongren Hospital affiliated to Capital Medical University from January to July 2022 were collected and divided into GATT group (undergoing GATT) and 3T group (undergoing 3T operation) using a random number table. Intraocular pressure (IOP) was recorded for both groups at 1 day, 1 week, 1 month, and 3 months after the operation, and the types and quantities of anti-glaucoma drugs used, postoperative complications, and surgical success rate were compared. Normal distribution measurement data were analyzed using independent sample t-tests, non-normal distribution measurement data were analyzed using non-parametric tests, and counting data were analyzed using chi-square tests. Results: This study included 35 patients (43 eyes), consisting of 27 males and 8 females, with an average age of (43.0±14.3) years. There were 21 patients (23 eyes) in the GATT group and 19 patients (20 eyes) in the 3T group. The maximum IOP without anti-glaucoma drugs before surgery, the highest IOP with the maximum number of anti-glaucoma drugs, and the IOP at 3 months after surgery in the GATT group were (33.5±9.1), (22.2±6.1), and (16.0±3.1) mmHg (1 mmHg=0.133 kPa), respectively. The corresponding values for the 3T group were (35.2±7.8), (21.5±6.8), and (16.1±2.0) mmHg. After surgery, the IOP in both groups was lower than before surgery, with a statistically significant difference (P<0.05) and no significant difference between the two groups (P>0.05). In the 3 months following surgery, 13 eyes in the GATT group and 11 eyes in the 3T group received more than two types of anti-glaucoma drugs, with no significant difference between the two groups (P>0.05). Three months after surgery, the complete and conditional success rates of the GATT group were 14/18 and 16/18, respectively, and those of the 3T group were 12/15 and 13/15, respectively, with no significant difference between the two groups (P>0.05). The incidence of hyphema, ciliary detachment, and shallow anterior chamber 1 day after surgery was 91%(21/23), 35%(8/23), and 30%(7/23), respectively, in the GATT group and 55%(11/20), 5%(1/20), and 0 in the 3T group, with a statistically significant difference between the two groups (P<0.05). Conclusion: 3T and GATT have similar success rates in the treatment of open-angle glaucoma. However, compared with GATT, 3T has fewer complications and is considered to be safer. (This article was published ahead of print on the Online-First Publishing Platform for Excellent Scientific Researches of Chinese Medical Association Publishing House on February 28, 2023).


Assuntos
Glaucoma de Ângulo Aberto , Trabeculectomia , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Glaucoma de Ângulo Aberto/diagnóstico , Estudos Prospectivos , Agentes Antiglaucoma , Seguimentos , Estudos Retrospectivos , Pressão Intraocular , Gonioscopia , Resultado do Tratamento
5.
Beijing Da Xue Xue Bao Yi Xue Ban ; 55(1): 70-77, 2023 Feb 18.
Artigo em Chinês | MEDLINE | ID: mdl-36718691

RESUMO

OBJECTIVE: To evaluate the characteristics of severe periodontitis with various number of tooth loss during 4-year natural progression, and to analyze the factors related to higher rate of tooth loss. METHODS: A total of 217 patients aged 15 to 44 years with severe periodontitis were included, who participated in a 4-year natural progression research. Data obtained from questionnaire survey, clinical examination and radiographic measurement. Tooth loss during 4-year natural progression was evaluated. The baseline periodontal disease related and caries related factors were calculated, including number of teeth with bone loss > 50%, number of missing molars, number of teeth with widened periodontal ligament space (WPDL), number of teeth with periapical lesions and etc. Characteristics of populations with various number of tooth loss and the related factors that affected higher rate of tooth loss were analyzed. RESULTS: In 4 years of natural progression, 103 teeth were lost, and annual tooth loss per person was 0.12±0.38. Nine patients lost 3 or more teeth. Thirty-four patients lost 1 or 2 teeth, and 174 patients were absent of tooth loss. Molars were mostly frequent to lose, and canines presented a minimum loss. The number of teeth with WPDL, with periapical lesions, with intrabony defects, with probing depth (PD)≥7 mm, with PD≥5 mm, with clinical attachment loss≥5 mm, with bone loss > 50% and with bone loss > 65% were positively correlated to number of tooth loss. Results from orderly multivariate Logistic regression showd that the number of teeth with bone loss > 50% OR=1.550), baseline number of molars lost (OR=1.774), number of teeth with WPDL (1 to 2: OR=1.415; ≥3: OR=13.105), number of teeth with periapical lesions (1 to 2: OR=4.393; ≥3: OR=9.526) and number of teeth with caries/residual roots (OR=3.028) were significant risk factors related to higher likelihood of tooth loss and multiple tooth loss. CONCLUSION: In 4 years of natural progression, the number of teeth with bone loss > 50%, baseline number of missing molars, number of teeth with WPDL, baseline number of teeth with periapical lesions and number of teeth with caries/residual roots were significantly related to higher risk of tooth loss and multiple tooth loss among Chinese young and middle-aged patients with severe periodontitis in rural areas.


Assuntos
Doenças Periodontais , Periodontite , Perda de Dente , Dente , Humanos , Perda de Dente/epidemiologia , Perda de Dente/etiologia , Periodontite/complicações , Dente Molar
6.
Physiol Res ; 72(6): 753-765, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38215062

RESUMO

Although cisplatin is an effective chemotherapy drug for the treatment of various cancers, its clinical use is limited due to its side effects, especially nephrotoxicity. Unfortunately, acute kidney injury (AKI) caused by cisplatin remains one of the main challenges in effective cancer treatment. Evidence increasingly suggests that renal inflammation and pyroptotic inflammatory cell death of renal tubular epithelial cells (RTECs) mainly determine the progression and outcome of cisplatin-induced AKI. However, it is not clear how cisplatin regulates the pyroptosis of RTECs cells in AKI. The current study aimed to determine the regulation mechanism of AKI induced by cisplatin. We used cisplatin to induce AKI in vivo. We performed H&E staining of mouse kidney tissue sections and evaluated serological indicators of kidney injury (including blood urea nitrogen (BUN), serum creatinine, and tumor necrosis factor-alpha (TNF-alpha)). We used immunohistochemistry and western blot to detect the important substrate protein gasdermin D (GSDMD) and key target caspase-1 of pyroptosis, respectively. Cisplatin induced mouse AKI and RTECs pyroptosis. HK2 cell-derived exosomes treated with cisplatin influenced pyroptosis of the surrounding HK2 cells. Cisplatin-treated HK2 cells exosome-derived miR-122 regulated pyroptosis in the surrounding cells. Exosome-derived miR-122 affected cisplatin-induced AKI and HK2 cells pyroptosis by regulating the expression of embryonic lethal abnormal vision (ELAVL1). These results suggest that exosome miR-122 inhibited pyroptosis and AKI by targeting ELAVL1 under cisplatin treatment, and this offers a potential target for the treatment of AKI.


Assuntos
Injúria Renal Aguda , Exossomos , MicroRNAs , Camundongos , Animais , Cisplatino/toxicidade , Piroptose , Exossomos/metabolismo , Exossomos/patologia , Injúria Renal Aguda/induzido quimicamente , MicroRNAs/metabolismo
7.
Biol Psychiatry ; 92(12): 942-951, 2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-36075764

RESUMO

BACKGROUND: Major depressive disorder is one of the most commonly diagnosed mental illnesses worldwide, with a higher prevalence in women than in men. Although currently available pharmacological therapeutics help many individuals, they are not effective for most. Animal models have been important for the discovery of molecular alterations in stress and depression, but difficulties in adapting animal models of depression for females has impeded progress in developing novel therapeutic treatments that may be more efficacious for women. METHODS: Using the California mouse social defeat model, we took a multidisciplinary approach to identify stress-sensitive molecular targets that have translational relevance for women. We determined the impact of stress on transcriptional profiles in male and female California mouse nucleus accumbens (NAc) and compared these results with data from postmortem samples of the NAc from men and women diagnosed with major depressive disorder. RESULTS: Our cross-species computational analyses identified Rgs2 (regulator of G protein signaling 2) as a transcript downregulated by social defeat stress in female California mice and in women with major depressive disorder. RGS2 plays a key role in signal regulation of neuropeptide and neurotransmitter receptors. Viral vector-mediated overexpression of Rgs2 in the NAc restored social approach and sucrose preference in stressed female California mice. CONCLUSIONS: These studies show that Rgs2 acting in the NAc has functional properties that translate to changes in anxiety- and depression-related behavior. Future studies should investigate whether targeting Rgs2 represents a novel target for treatment-resistant depression in women.


Assuntos
Transtorno Depressivo Maior , Núcleo Accumbens , Animais , Feminino , Masculino , Camundongos , Depressão/tratamento farmacológico , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/metabolismo , Estresse Psicológico , Modelos Animais de Doenças , Comportamento Animal , Comportamento Social , Camundongos Endogâmicos C57BL
8.
Hum Exp Toxicol ; 41: 9603271221129852, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36137816

RESUMO

Lipid metabolism is an important biochemical process in the body. Recent studies have found that environmental endocrine disruptors play an important role in the regulation of lipid metabolism. Bisphenol A (BPA), a common environmental endocrine disruptor, has adverse effects on lipid metabolism, but the mechanism is still unclear. This study aimed to investigate the effects of gestational BPA exposure on hepatic lipid metabolism and its possible mechanism in male offspring. The pregnant Sprague-Dawley rats were exposed to BPA (0, 0.05, 0.5, 5 mg/kg/day) from day 5 to day 19 of gestation to investigate the levels of triglyceride (TG) and total cholesterol (TC), and the expression of liver lipid metabolism-related genes in male offspring rats. The results showed that compared with the control group, the TG and TC levels in serum and liver in BPA-exposed groups was increased. And the expressions of liver fatty acid oxidation related genes, such as peroxisome proliferators-activated receptor α (PPARα) and carnitine palmitoyl transferase 1α (CPT1α), were down-regulated. However, the expressions of fatty acid synthesis related genes, such as sterol regulatory element binding proteins 1 (SREBP-1), acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD-1), were up-regulated. The increased protein levels of mTOR and p-CRTC2 suggested that CREB-regulated transcription coactivator 2 (CRTC2) might be an important mediator in the mTOR/SREBP-1 pathway. In conclusion, these results demonstrated that mTOR/CRTC2/SREBP-1 could be affected by gestational BPA exposure, which may involve in the lipid metabolic disorders in later life.


Assuntos
Disruptores Endócrinos , Metabolismo dos Lipídeos , Acetil-CoA Carboxilase/metabolismo , Acetil-CoA Carboxilase/farmacologia , Animais , Compostos Benzidrílicos , Carnitina/farmacologia , Colesterol , Disruptores Endócrinos/toxicidade , Ácido Graxo Sintases/metabolismo , Ácido Graxo Sintases/farmacologia , Ácidos Graxos/farmacologia , Feminino , Fígado , Masculino , PPAR alfa/metabolismo , Proliferadores de Peroxissomos/metabolismo , Proliferadores de Peroxissomos/farmacologia , Fenóis , Gravidez , Ratos , Ratos Sprague-Dawley , Estearoil-CoA Dessaturase/metabolismo , Estearoil-CoA Dessaturase/farmacologia , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Transferases/metabolismo , Transferases/farmacologia , Triglicerídeos
9.
Ann Oncol ; 33(12): 1284-1295, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36089134

RESUMO

BACKGROUND: Studies of targeted therapy resistance in lung cancer have primarily focused on single-gene alterations. Based on prior work implicating apolipoprotein b mRNA-editing enzyme, catalytic polypeptide-like (APOBEC) mutagenesis in histological transformation of epidermal growth factor receptor (EGFR)-mutant lung cancers, we hypothesized that mutational signature analysis may help elucidate acquired resistance to targeted therapies. PATIENTS AND METHODS: APOBEC mutational signatures derived from an Food and Drug Administration-cleared multigene panel [Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT)] using the Signature Multivariate Analysis (SigMA) algorithm were validated against the gold standard of mutational signatures derived from whole-exome sequencing. Mutational signatures were decomposed in 3276 unique lung adenocarcinomas (LUADs), including 93 paired osimertinib-naïve and -resistant EGFR-mutant tumors. Associations between APOBEC and mechanisms of resistance to osimertinib were investigated. Whole-genome sequencing was carried out on available EGFR-mutant lung cancer samples (10 paired, 17 unpaired) to investigate large-scale genomic alterations potentially contributing to osimertinib resistance. RESULTS: APOBEC mutational signatures were more frequent in receptor tyrosine kinase (RTK)-driven lung cancers (EGFR, ALK, RET, and ROS1; 25%) compared to LUADs at large (20%, P < 0.001); across all subtypes, APOBEC mutational signatures were enriched in subclonal mutations (P < 0.001). In EGFR-mutant lung cancers, osimertinib-resistant samples more frequently displayed an APOBEC-dominant mutational signature compared to osimertinib-naïve samples (28% versus 14%, P = 0.03). Specifically, mutations detected in osimertinib-resistant tumors but not in pre-treatment samples significantly more frequently displayed an APOBEC-dominant mutational signature (44% versus 23%, P < 0.001). EGFR-mutant samples with APOBEC-dominant signatures had enrichment of large-scale genomic rearrangements (P = 0.01) and kataegis (P = 0.03) in areas of APOBEC mutagenesis. CONCLUSIONS: APOBEC mutational signatures are frequent in RTK-driven LUADs and increase under the selective pressure of osimertinib in EGFR-mutant lung cancer. APOBEC mutational signature enrichment in subclonal mutations, private mutations acquired after osimertinib treatment, and areas of large-scale genomic rearrangements highlights a potentially fundamental role for APOBEC mutagenesis in the development of resistance to targeted therapies, which may be potentially exploited to overcome such resistance.


Assuntos
Adenocarcinoma de Pulmão , Cromotripsia , Neoplasias Pulmonares , Humanos , Proteínas Tirosina Quinases/genética , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas Proto-Oncogênicas/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Compostos de Anilina/farmacologia , Compostos de Anilina/uso terapêutico , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Receptores Proteína Tirosina Quinases/genética , Mutagênese , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico
10.
Horm Behav ; 143: 105203, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35636023

RESUMO

Oxytocin is a neuropeptide that can produce anxiolytic effects and promote social approach. However, emerging evidence shows that under some conditions, oxytocin can instead induce anxiety-related behaviors. These diverse effects of oxytocin appear to be mediated by circuit-specific actions. Recent data showed that inhibition of oxytocin receptors (OTRs) in the bed nucleus of the stria terminalis (BNST) was sufficient to increase social approach and decrease social vigilance in female California mice (Peromyscus californicus) exposed to social defeat stress. As a member of the G-protein coupled receptor family, OTRs can induce distinct downstream pathways by coupling to different G-protein isoforms. We show that infusion of carbetocin, a biased OTR-Gq agonist, in the BNST reduced social approach in both female and male California mice. In both females and males, carbetocin also increased social vigilance. To gain insight into cell types that could be mediating this effect, we analyzed previously published single-cell RNAseq data from the BNST and nucleus accumbens (NAc). In the NAc, we and others showed that OTR activation promotes social approach behaviors. In the BNST, Oxtr was expressed in over 40 cell types, that span both posterior and anterior subregions of the BNST. The majority of Oxtr-expressing neurons were GABAergic. In the anterior regions of BNST targeted in our carbetocin experiments, Cyp26b1-expressing neurons had high average Oxtr expression. In the NAc, most Oxtr+ cells were D1 dopamine receptor-expressing neurons and interneurons. These differences in Oxtr cell type distribution may help explain how activation of OTR in BNST versus NAc can have different effects on social approach and social vigilance.


Assuntos
Núcleos Septais , Animais , Feminino , Masculino , Núcleo Accumbens/metabolismo , Ocitocina/metabolismo , Ocitocina/farmacologia , Receptores de Dopamina D1/metabolismo , Receptores de Ocitocina/metabolismo , Núcleos Septais/metabolismo , Comportamento Social
11.
Sci Rep ; 12(1): 4114, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35260773

RESUMO

Polymer composites are gradually replacing traditional metal materials in the fields of aviation, aerospace, automotive and medicine due to their corrosion resistance, light weight and high strength. Moulding technology and organization morphology of polymer composite are key elements affecting the quality of products and their application, so a vacuum hot pressing process for graphenex/poly(ether ketone ketone) (PEKK) (x = 0%, 2%, 3%, 4%, 5%, 6%) composite powders is explored with particularly designed moulding parameters to achieve high conductive properties and good mechanical properties in graphene/PEKK composite sheet with thickness of 1.25 mm and diameter of 80 mm. The vacuum environment ensures that the graphene is not oxidized by air during hot pressing molding, which is essential for achieving conductive property in the graphene/PEKK composite; The hot pressing temperature of each graphene/PEKK composite powder is higher than glass transition temperature but lower than melting temperature, which ensures the graphene/PEKK composite powders is fully compacted and then graphene is fully lapped in the composite sheet. In addition, the graphene/PEKK composite sheet shows conductive property when the graphene content increases to 3wt%, and then the conductivity of the composites increases and then decreases with a peak value at 5wt% with increasing graphene content. By comparing the mechanical properties and microstructure morphology of the graphene/PEKK composite sheets, it was obtained that graphene content has an obvious effect on the mechanical properties of the composites, e.g., the mechanical properties will be increased as the graphene content increasing when graphene content is more than 3%. The graphene distribution law of the composite material with different graphene contents is analysed using a scanning electron microscope (SEM).

13.
Nat Commun ; 12(1): 4791, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373452

RESUMO

Classical dendritic cells (cDC) are professional antigen-presenting cells (APC) that regulate immunity and tolerance. Neutrophil-derived cells with properties of DCs (nAPC) are observed in human diseases and after culture of neutrophils with cytokines. Here we show that FcγR-mediated endocytosis of antibody-antigen complexes or an anti-FcγRIIIB-antigen conjugate converts neutrophils into nAPCs that, in contrast to those generated with cytokines alone, activate T cells to levels observed with cDCs and elicit CD8+ T cell-dependent anti-tumor immunity in mice. Single cell transcript analyses and validation studies implicate the transcription factor PU.1 in neutrophil to nAPC conversion. In humans, blood nAPC frequency in lupus patients correlates with disease. Moreover, anti-FcγRIIIB-antigen conjugate treatment induces nAPCs that can activate autologous T cells when using neutrophils from individuals with myeloid neoplasms that harbor neoantigens or those vaccinated against bacterial toxins. Thus, anti-FcγRIIIB-antigen conjugate-induced conversion of neutrophils to immunogenic nAPCs may represent a possible immunotherapy for cancer and infectious diseases.


Assuntos
Antígenos de Neoplasias/imunologia , Neoplasias/imunologia , Neutrófilos/imunologia , Receptores de IgG/genética , Receptores de IgG/imunologia , Proteínas Adaptadoras de Transporte Vesicular/genética , Animais , Apresentação de Antígeno/imunologia , Complexo Antígeno-Anticorpo , Medula Óssea , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Movimento Celular , Proliferação de Células , Citocinas/imunologia , Células Dendríticas/imunologia , Endocitose , Humanos , Imunidade Inata , Imunoterapia , Linfonodos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/genética , Espécies Reativas de Oxigênio , Transcriptoma
14.
Zhonghua Xue Ye Xue Za Zhi ; 42(6): 452-458, 2021 Jun 14.
Artigo em Chinês | MEDLINE | ID: mdl-34384150

RESUMO

Objectives: To verify the effects and mechanisms of natural MSC-exosome in treating acute GVHD in mice, explore and establish a method for targeted modification of MSC-exosome, and verify the functions of the modified MSC-exosome. Methods: In different doses of MSC-exosome groups and MSC group, weight loss in acute GVHD mice was observed; then the proliferation levels of activated T cells were measured through T cell activation experiment in vitro and OVA antigen-specific T cell activation experiment in vivo. AAV2YF3 mutants carrying PD-L1 and PD-L1-ITGB1 were obtained after the construction of recombinant expression vectors and were then applied to infect human MSC to modify their exosome. The immunoregulatory functions of the modified MSC-exosome were measured with the abovementioned methods. Results: ①Mouse MSC-exosome (300 µg×3 times) and MSC (1×10(6)×3 times) effectively alleviated the weight loss in acute GVHD mice. ②Compared with IL-2, 10, 25 and 50 µg human MSC-exosome inhibited the proliferation of activated T cells in vitro, respectively, 86.0% (IL-2) , 40.0%, 39.6%, and 42.8%; compared with PBS, 50, 100 and 200 µg mouse MSC-exosome inhibited the proliferation of antigen-specific activated OT-1 cells in vivo, respectively, 42.6%, 33.1%, 14.2%, and 10.6%. ③After the infection of AAV2YF3 mutant carrying PD-L1 or PD-L1-ITGB1, the positive proportion of MSC-exosome exceeds 40% and 60%, respectively. ④Compared with the natural state, MSC-exosome modified by PD-L1 or PD-L1-ITGB1 showed better proliferation inhibitory effect in vivo and increased the proportion of Treg cells in vitro. Conclusions: MSC-exosome exhibited similar immunomodulatory effects with MSC. MSC-exosome after PD-L1 and PD-L1-ITGB1-targeted modification effectively inhibited the proliferation of activated T cells and increased the proportion of Treg cells.


Assuntos
Exossomos , Doença Enxerto-Hospedeiro , Células-Tronco Mesenquimais , Animais , Dependovirus/genética , Humanos , Camundongos , Linfócitos T Reguladores
15.
Behav Brain Res ; 401: 113084, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33358922

RESUMO

Women are more likely to suffer from stress-related affective disorders than men, but the underlying mechanisms of sex differences remain unclear. Previous works show that microRNA (miRNA) profiles are altered in stressed animals and patients with depression and anxiety disorders. In this study, we investigated how miRNA expression in the anterior bed nucleus of stria terminalis (BNST) was affected by social defeat stress in female and male California mice (Peromyscus californicus). We performed sequencing to identify miRNA transcripts in the whole brain and anterior BNST followed by qPCR analysis to compare miRNA expression between control and stressed animals. The results showed that social defeat stress induced sex-specific miRNA expression changes in the anterior BNST. Let-7a, let-7f and miR-181a-5p were upregulated in stressed female but not male mice. Our study provided evidence that social stress produces distinct molecular responses in the BNST of males and females.


Assuntos
Comportamento Animal/fisiologia , MicroRNAs/metabolismo , Núcleos Septais/metabolismo , Caracteres Sexuais , Derrota Social , Estresse Psicológico/metabolismo , Animais , Feminino , Masculino , Peromyscus , Análise de Sequência de RNA , Regulação para Cima
16.
Nature ; 586(7831): 693-696, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33116290

RESUMO

Fast radio bursts (FRBs) are millisecond-duration radio transients1,2 of unknown origin. Two possible mechanisms that could generate extremely coherent emission from FRBs invoke neutron star magnetospheres3-5 or relativistic shocks far from the central energy source6-8. Detailed polarization observations may help us to understand the emission mechanism. However, the available FRB polarization data have been perplexing, because they show a host of polarimetric properties, including either a constant polarization angle during each burst for some repeaters9,10 or variable polarization angles in some other apparently one-off events11,12. Here we report observations of 15 bursts from FRB 180301 and find various polarization angle swings in seven of them. The diversity of the polarization angle features of these bursts is consistent with a magnetospheric origin of the radio emission, and disfavours the radiation models invoking relativistic shocks.

17.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(5): 586-592, 2020 May 06.
Artigo em Chinês | MEDLINE | ID: mdl-32388965

RESUMO

As an important method to study the phenotype and function of organisms, transcriptome has become one of hot topics in current research. The transcriptomics research usually accompanies with massive data. With the increase of the amount of data, the rules and features hidden in it are not easy to be found. Transforming big data into visual graphics is the most undoubtedly intuitive way to display the hidden information of big data. Several graphs commonly used in transcriptome study were introduced in this paper, such as Venn diagram, heat map, principal component analysis scatter plot, enrichment analysis plot, and time series analysis plot, in order to help readers to choose suitable graphics in future studies.


Assuntos
Biologia Computacional , Gráficos por Computador , Transcriptoma , Big Data , Software
18.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(2): 175-180, 2020 Feb 06.
Artigo em Chinês | MEDLINE | ID: mdl-32074706

RESUMO

Objective: To analyze the molecular characteristics of Listeria monocytogenes strains from ready-to eat food in China. Methods: A total of 239 Listeria monocytogenes strains isolated from ready-to-eat food in 2017, all strains underwent whole-genome sequencing (WGS) , and comparisons uncovered population structure derived from lineages, clonal complex, serogroups, antimicrobial susceptibility and virulence, which were inferred in silico from the WGS data. Core genome multilocus sequence typing was used to subtype isolates. Results: All strains were categorized into three different lineages, lineage Ⅱ was the predominant types in food, and IIa was the main serogroups. CC8, CC101 and CC87 were the first three prevalent CCs among 23 detected CCs, accounting for 49.4%. Only 4.6% (11 isolates) of tested strains harbored antibiotic resistance genes, which were mostly trimethoprim genes (7 isolates, 2.9%). All strains were positive for LIPI-1, and only a part of strains harbored LIPI-3 and LIPI-4, accounting for 13.8% (33 isolates) and 14.2% (34 isolates), respectively. ST619 carried both LIPI-3 and LIPI-4. 51.5% (123 isolates) of strains carried SSI-1, and all CC121 strains harbored SSI-2. Different lineages, serogroups and CCs can be separated obviously through cgMLST analysis, and 24 sublineages were highly concordant with CCs. Conclusion: Ⅱa was the main serogroups in ready-to-eat food isolates in China; CC8, CC101 and CC87 were the prevalent CCs, and CC87 isolates was hypervirulent isolates, cgMLST method can be adopted for prospective foodborne disease surveillance and outbreaks detection.


Assuntos
Microbiologia de Alimentos , Listeria monocytogenes/isolamento & purificação , Listeriose/microbiologia , China/epidemiologia , Humanos , Listeriose/epidemiologia
19.
Public Health ; 175: 54-59, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31398517

RESUMO

OBJECTIVES: The objective of this study to determine whether body mass index (BMI) in different genders and age groups need different thresholds when predicting chronic non-communicable diseases (CNCDs). STUDY DESIGN: This is a cross-sectional study. METHODS: Data were obtained from the China Health and Nutrition Survey conducted in 2009. Sequential sample cluster analysis was used to group age according to BMI. Propensity score matching was used to eliminate the influence of age. Receiver operating characteristic curve based on gender and age group was used to evaluate the cut-off values and efficiency of BMI in each group. RESULTS: A total of 8469 individuals were enrolled in this study. Results of sequential sample cluster analyses showed age was divided into three groups: 18-39, 40-59 and 60-99 years. There were significant differences in the distribution of BMI among the three groups for both males and females (P < 0.001). Statistical differences were observed in the distribution of BMI between genders in the 18-39- and 60-99-year-old age groups (P < 0.001). For men, the cut-off values of BMI were ≥25 kg/m2, ≥24 kg/m2 and ≥23 kg/m2 in the 18-39, 40-59 and 60-99 years old groups, respectively; for women, the corresponding cut-off points were ≥25 kg/m2, ≥23 kg/m2 and ≥25 kg/m2 in groups. CONCLUSIONS: The thresholds for BMI might be different between gender and age group. In addition, it might not be suitable to determine cut-off values of BMI to predict CNCDs for people aged ≥60 years.


Assuntos
Índice de Massa Corporal , Doença Crônica/epidemiologia , Doenças não Transmissíveis/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Valores de Referência , Distribuição por Sexo , Adulto Jovem
20.
Development ; 146(5)2019 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-30846463

RESUMO

Kidney organoids have potential uses in disease modelling, drug screening and regenerative medicine. However, novel cost-effective techniques are needed to enable scaled-up production of kidney cell types in vitro We describe here a modified suspension culture method for the generation of kidney micro-organoids from human pluripotent stem cells. Optimisation of differentiation conditions allowed the formation of micro-organoids, each containing six to ten nephrons that were surrounded by endothelial and stromal populations. Single cell transcriptional profiling confirmed the presence and transcriptional equivalence of all anticipated renal cell types consistent with a previous organoid culture method. This suspension culture micro-organoid methodology resulted in a three- to fourfold increase in final cell yield compared with static culture, thereby representing an economical approach to the production of kidney cells for various biological applications.


Assuntos
Técnicas de Cultura de Células , Regulação da Expressão Gênica no Desenvolvimento , Rim/citologia , Células-Tronco Pluripotentes/citologia , Albuminas/metabolismo , Diferenciação Celular , Células Cultivadas , Doxorrubicina/farmacologia , Humanos , Néfrons/metabolismo , Organoides , Transdução de Sinais , Transcrição Gênica , Proteínas Wnt/metabolismo
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