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1.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1010279

RESUMO

Diabetic kidney disease (DKD) is the primary cause of mortality among diabetic patients. With the increasing prevalence of diabetes, it has become a major concern around the world. The therapeutic effect of clinical use of drugs is far from expected, and therapy choices to slow the progression of DKD remain restricted. Therefore, research on new drugs and treatments for DKD has been a hot topic in the medical field. It has been found that rhein has the potential to target the pathogenesis of DKD and has a wide range of pharmacological effects on DKD, such as anti-nephritis, decreasing blood glucose, controlling blood lipids and renal protection. In recent years, the medical value of rhein in the treatment of diabetes, DKD and renal disease has gradually attracted worldwide attention, especially its potential in the treatment of DKD. Currently, DKD can only be treated with medications from a single symptom and are accompanied by adverse effects, while rhein improves DKD with a multi-pathway and multi-target approach. Therefore, this paper reviews the therapeutic effects of rhein on DKD, and proposes solutions to the limitations of rhein itself, in order to provide valuable references for the clinical application of rhein in DKD and the development of new drugs.


Assuntos
Humanos , Nefropatias Diabéticas/tratamento farmacológico , Rim/patologia , Antraquinonas/uso terapêutico , Diabetes Mellitus
2.
Chinese Medical Journal ; (24): 295-304, 2023.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-970073

RESUMO

Estrogen impacts neural development; meanwhile, it has a protective effect on the brain. Bisphenols, primarily bisphenol A (BPA), can exert estrogen-like or estrogen-interfering effects by binding with estrogen receptors. Extensive studies have suggested that neurobehavioral problems, such as anxiety and depression, can be caused by exposure to BPA during neural development. Increasing attention has been paid to the effects on learning and memory of BPA exposure at different developmental stages and in adulthood. Further research is required to elucidate whether BPA increases the risk of neurodegenerative diseases and the underlying mechanisms, as well as to assess whether BPA analogs, such as bisphenol S and bisphenol F, influence the nervous system.


Assuntos
Receptores de Estrogênio/metabolismo , Estrogênios , Compostos Benzidrílicos/farmacologia , Sistema Nervoso/metabolismo
3.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-978471

RESUMO

Diabetic cardiomyopathy (DCM) is one of the complications of diabetes. It refers to a specific type of idiopathic cardiomyopathy that occurs in individuals with diabetes, distinct from other cardiovascular diseases such as coronary heart disease, valvular heart disease, or congenital heart disease. It has also been identified as one of the leading causes of death in diabetic patients for many years. Research has shown that the pathogenesis of DCM is closely associated with insulin resistance, activation of various inflammatory responses, increased oxidative stress, impaired coronary microcirculation, and accumulation of advanced glycation end products (AGEs). Among various inflammatory responses, the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome can induce the secretion of a large amount of pro-inflammatory cytokines through the cascade reaction of inflammation, subsequently mediating cellular pyroptosis and promoting myocardial damage. Currently, extensive experimental studies on traditional Chinese medicine (TCM) have been conducted in China and abroad based on the significant role of the NLRP3 inflammasome in the prevention and treatment of DCM. These studies have demonstrated that Chinese medicinal extracts, such as Astragalus polysaccharide and ginsenoside Rb1, single drugs like Coriolus and Cordyceps, and Chinese medicinal formulas like Didangtang and modified Taohe Chengqitang, as well as acupuncture and TCM exercise therapy, can regulate the relevant pathways of the NLRP3 inflammasome to inhibit its assembly or activation, reduce inflammatory responses, inhibit myocardial remodeling in DCM, and improve cardiac function. This article reviewed the relationship between the NLRP3 inflammasome and DCM, as well as the research progress on TCM in exerting anti-inflammatory effects in this field, aiming to provide new insights for the development of therapeutic approaches for DCM.

4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-993165

RESUMO

Objective:To develop the real-time radiotherapy monitoring system of three-dimensional (3D) point cloud by using depth camera and verify its feasibility.Methods:Taking the depth camera coordinate system as the world coordinate system, the conversion relationship between the simulation CT coordinate system and the world coordinate system was obtained from the calibration module. The patient's simulation CT point cloud was transformed into the world coordinate system through the above relationship, and registered with the patient's surface point cloud obtained in real-time manner by the depth camera to calculate the six-dimensional (6D) error, and complete the positioning verification and fractional internal position error monitoring in radiotherapy. Mean and standard deviation of 6D calculation error, Hausdorff distance of point cloud after registration and the running time of each part of the program were calculated to verify the feasibility of the system. Fifteen real patients were selected to calculate the 6D error between the system and cone beam CT (CBCT).Results:In the phantom experiment, the errors of the system in the x, y and z axes were (1.292±0.880)mm, (1.963±1.115)mm, (1.496±1.045)mm, respectively, and the errors in the rotation, pitch and roll directions were 0.201°±0.181°, 0.286°±0.326°, 0.181°±0.192°, respectively. For real patients, the translational error of the system was within 2.6 mm, the rotational error was approximately 1°, and the program run at 1-2 frames/s. The precision and speed met the radiotherapy requirement. Conclusion:The 3D point cloud radiotherapy real-time monitoring system based on depth camera can automatically complete the positioning verification before radiotherapy, real-time monitoring of body position during radiotherapy, and provide error visual feedback, which has potential clinical application value.

5.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-993054

RESUMO

Image-guided radiation therapy (IGRT) is a visual image-guided radiotherapy technique that has many advantages such as increasing the dose of tumor target area and reducing the dose of normal organ exposure. Cone beam CT (CBCT) is one of the most commonly used medical images in IGRT, and the rapid and accurate targeting of CBCT and the segmentation of dangerous organs are of great significance for radiotherapy. The current research method mainly includes partitioning method based on registration and segmentation method based on deep learning. This study reviews the CBCT image segmentation method, existing problems and development directions.

6.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-990235

RESUMO

Objective:To explore the clinical effectiveness of hemostatic bandage on wound safety and comfort after transradial coronary angiography and/or interventional therapy.Methods:This was a experimental study. A total of 400 consecutive patients who underwent transradial coronary angiography and/or interventional therapy in the Department of Cardiology, Peking University Third Hospital from July to October 2022 were enrolled and randomly divided into the hemostatic bandage group and the hemostatic balloon compressor group by the envelope method with 200 cases in each group. The hemostatic bandage group and the hemostatic balloon compressor group were treated with hemostatic bandage and hemostatic balloon compressor as transradial artery hemostatic device, respectively, to observe and compare postoperative hemostatic effect, hemostat use time, complication rate, postoperative pain, the degree of numbness in the finger on the operated side and wristband comfort between the two groups.Results:The hemostatic success rate was 98.5% (197/200) and 99.0% (198/200) in the hemostatic bandage and the hemostatic balloon compressor group, respectively, with no statistical difference ( χ2=0.20, P>0.05). The hemostat use time in the hemostatic bandage group and the hemostatic balloon compressor group was (6.23 ± 0.47) h and (17.01 ± 7.74) h, respectively, and the difference was statistically significant ( t=-19.66, P<0.01). The incidence of complications in the hemostatic bandage group and the hemostatic balloon compressor group was 13.5%(27/200) and 29.5%(59/200), respectively, and the difference was statistically significant ( χ2=8.01, P<0.05). Among the complications, swelling occurred in 21 individuals of the hemostatic bandage group and 54 individuals of the hemostatic balloon compressor group with statistically significant differences ( U=16 689.50, P<0.01). Besides, the hemostatic bandage group was significantly better than the hemostatic balloon compressor group with statistically significant differences in wound pain at immediate postoperative ( U=13 669.50, P<0.01), in finger numbness at immediate postoperative and 1-hour postoperative (immediate postoperative: U=17 838.00, P<0.05; 1-hour postoperative: U=13 342.50, P<0.01), in comfort at immediate postoperative, 4-hours, 8-hours and 12-hour postoperative(immediate postoperative: U=9 966.50, P<0.01; 4-hour postoperative: U=12 851, P<0.01; 8-hour postoperative: U=14 900, P<0.01; 12-hour postoperative: U=15 920, P<0.01). Conclusions:The hemostatic bandage shows better hemostatic effect, shorter compression time, lower complication rate, less wound pain, less numbness of the finger on the operation side, and higher comfort of the wrist band compared to hemostatic balloon compressor after transradial coronary angiography and/or interventional therapy, which is worthy of clinical promotion.

7.
Acta Physiologica Sinica ; (6): 503-511, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1007765

RESUMO

In this study, we investigated the effects of Panax notoginseng saponins (PNS) on pulmonary vascular remodeling and ADAM10/Notch3 pathway in pulmonary arterial hypertension (PAH). PAH rat model was established, and male Sprague Dawley (SD) rats were randomly divided into control group, monocrotaline (MCT) group and MCT+PNS group, with 10 rats in each group. Rats in the control group were intraperitoneally injected with equal volume of normal saline. Rats in the MCT group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with the same volume of normal saline every day. Rats in the MCT+PNS group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with 50 mg/kg PNS every day. The modeling time of each group lasted for 21 days. After the model was established, the mean pulmonary artery pressure (mPAP) was measured by right heart catheterization technique, the right ventricular hypertrophy index (RVHI) was calculated, the microscopic morphology and changes of pulmonary vascular wall were observed by HE and Masson staining, and the expressions of ADAM10, Notch3, Hes-1, P27, PCNA, Caspase-3 proteins and mRNA in pulmonary vascular tissue of rats were detected by Western blot and qPCR. The expression and localization of Notch3 and α-SMA were detected by immunofluorescence staining. The protein expression of ADAM10 was detected by immunohistochemical staining. The results showed that compared with the control group, mPAP, RVHI, pulmonary vessels and collagen fibers in the MCT group were significantly increased, the expressions of ADAM10, Notch3, Hes-1, and PCNA protein and mRNA were significantly increased, while the expressions of P27 and Caspase-3 protein and mRNA were decreased significantly. Compared with the MCT group, mPAP and RVHI were significantly decreased, pulmonary vessels were significantly improved and collagen fibers were significantly reduced, the expressions of protein and mRNA of ADAM10, Notch3, Hes-1, and PCNA were decreased in MCT+PNS group, but the expressions of protein and mRNA of P27 and Caspase-3 were increased slightly. The results of immunofluorescence showed that Notch3 and α-SMA staining could overlap, which proved that Notch3 was expressed in smooth muscle cells. The expression of Notch3 in the MCT group was increased significantly compared with that in the control group, while PNS intervention decreased the expression of Notch3. Immunohistochemical staining showed that compared with the control group, the amount of ADAM10 in the MCT group was increased significantly, and the expression of ADAM10 in the MCT+PNS group was decreased compared with the MCT group. These results indicate that PNS can improve the PAH induced by MCT in rats by inhibiting ADAM10/Notch3 signaling pathway.


Assuntos
Animais , Masculino , Ratos , Caspase 3/metabolismo , Colágeno , Modelos Animais de Doenças , Hipertensão Pulmonar/tratamento farmacológico , Monocrotalina/efeitos adversos , Panax notoginseng/química , Antígeno Nuclear de Célula em Proliferação/farmacologia , Hipertensão Arterial Pulmonar , Artéria Pulmonar/metabolismo , Ratos Sprague-Dawley , Receptor Notch3/genética , RNA Mensageiro , Solução Salina , Transdução de Sinais , Saponinas/farmacologia
8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-985447

RESUMO

Polycystic ovary syndrome (PCOS) is a common endocrine disease in women of childbearing age, which seriously affects women's reproductive health. In recent years, more and more studies have found that serum anti-Müllerian hormone (AMH) has certain significance in the diagnosis and treatment evaluation of PCOS. In addition, with the improvement of detection methods, more attention has been paid to the significance of female androgens and AMH in the evaluation of PCOS. This article reviews the recent research progress of serum AMH and androgens in the evaluation of PCOS.


Assuntos
Feminino , Humanos , Síndrome do Ovário Policístico/diagnóstico , Androgênios , Hormônio Antimülleriano
9.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-483172

RESUMO

New therapeutic targets are a valuable resource in the struggle to reduce the morbidity and mortality associated with the COVID-19 pandemic, caused by the SARS-CoV-2 virus. Genome-wide association studies (GWAS) have identified risk loci, but some loci are associated with co-morbidities and are not specific to host-virus interactions. Here, we identify and experimentally validate a link between reduced expression of EXOSC2 and reduced SARS-CoV-2 replication. EXOSC2 was one of 332 host proteins examined, all of which interact directly with SARS-CoV-2 proteins; EXOSC2 interacts with Nsp8 which forms part of the viral RNA polymerase. Lung-specific eQTLs were identified from GTEx (v7) for each of the 332 host proteins. Aggregating COVID-19 GWAS statistics for gene-specific eQTLs revealed an association between increased expression of EXOSC2 and higher risk of clinical COVID-19 which survived stringent multiple testing correction. EXOSC2 is a component of the RNA exosome and indeed, LC-MS/MS analysis of protein pulldowns demonstrated an interaction between the SARS-CoV-2 RNA polymerase and the majority of human RNA exosome components. CRISPR/Cas9 introduction of nonsense mutations within EXOSC2 in Calu-3 cells reduced EXOSC2 protein expression, impeded SARS-CoV-2 replication and upregulated oligoadenylate synthase (OAS) genes, which have been linked to a successful immune response against SARS-CoV-2. Reduced EXOSC2 expression did not reduce cellular viability. OAS gene expression changes occurred independent of infection and in the absence of significant upregulation of other interferon-stimulated genes (ISGs). Targeted depletion or functional inhibition of EXOSC2 may be a safe and effective strategy to protect at-risk individuals against clinical COVID-19.

10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-930935

RESUMO

Objective:To investigate the clinical efficacy of avatrombopag combined with recombinant human thrombopoietin (rhTPO) versus avatrombopag in the treatment of severe thrombocytopenia associated with chronic liver disease.Methods:The retrospective cohort study was conducted. The clinical data of 56 patients with severe thrombocytopenia associated with chronic liver disease who were admitted to the First Affiliated Hospital of University of Science and Technology of China from May 2020 to October 2021 were collected. There were 36 males and 20 females, aged from 33 to 74 years, with a median age of 54 years. Of 56 patients, 21 cases undergoing treatment of avatrombopag combined with rhTPO were allocated into the combined treatment group and 35 cases undergoing treatment of avatrombopag were allocated into the monotherapy group. Observation indicators: (1) changes of platelet after treatment; (2) adverse drug reaction. Follow-up was conducted using outpatient examination and telephone interview to detect changes of platelet and effects of treatment within 2 weeks after treatment. The follow-up was up to October 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and compari-son between groups was analyzed using the chi-square test or Fisher exact probability. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Changes of platelet after treatment. The platelet level within 1 to 5 days and 6 to 10 days after treatment in the combined treatment group were (35±19)×10 9/L and (73±41)×10 9/L, respectively. The above indicators of the monotherapy group were (40±30)×10 9/L and (70±51)×10 9/L, respectively. There was no significant difference in change trends of platelet before and after treatment between the two groups ( Fgroup=0.30, P>0.05). There was a significant difference in platelet count before and after treatment between the two groups ( Ftime=59.96, P<0.05). There was no interaction effect in change trends of platelet between the two groups ( Finteraction=0.40, P>0.05). The effective rates were 66.67%(14/21) in the combination therapy group and 54.29%(19/35) in the monotherapy group. There was no significant difference in the effective rate between the two groups ( χ2=0.83, P>0.05). (2) Adverse drug reaction. Cases with headache, dizziness, blood transfusion reaction, hematuria, proteinuria, fever, abdominal pain, diarrhea, dyspepsia, fatigue, nausea or peripheral tissue edema were 2, 4, 1, 2, 2, 7, 10, 6, 8, 14, 12, 5 in the combined treatment group, versus 5, 8, 1, 3, 5, 7, 19, 11,20, 19, 14, 5 in the monotherapy group, respectively. There was no significant difference in cases with headache, dizziness, blood transfusion reaction, hematuria, proteinuria between the two groups ( P>0.05), and there was no significant difference in cases with fever, abdominal pain, diarrhea, dyspepsia, fatigue, nausea, peripheral tissue edema between the two groups ( χ2=1.24, 0.23, 0.05, 1.91, 0.83, 2.04, 0.81, P>0.05). Conclusion:Both of avatrombopag combined with rhTPO and monotherapy of avatrom-bopag can be used to promote the platelet level in patients with severe thrombocytopenia associated with chronic liver disease, and avatrombopag combined with rhTPO does not provide better clinical benefits compared with monotherapy avatrombopag.

11.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-957000

RESUMO

Objective:To investigate the protective effect of IL-22 on rat liver ischemia reperfusion injury (IRI) and the potential mechanisms.Methods:Eighteen male specific pathogen free SD rats (7-8 weeks, about 250g) were randomly divided into three groups: Sham group (Sham), hepatic ischemia reperfusion (IRI) and IL-22 preconditioning group (IL-22+ IRI), respectively. The liver IRI model of 70% rats was established. The IL-22+ IRI group was intraperitoneally injected with rcIL-22 (50 mg/kg) 1 hour before surgery, and the Sham group and IRI group were injected with the same dose of normal saline 1 hour before surgery. After 1 h ischemia and 6 h reperfusion, blood was collected from the abdominal aorta, then liver tissue, serum aspartate transaminase (AST) and alanine aminotransfease (ALT) levels were measured. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in liver tissue were detected. The expression of signal transducer and activator of transcription 3 (STAT3), p-STAT3, nuclear factor erythorid-2 related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) were detected by Western blot. Results:Compared with Sham group, serum AST [(1 923.50±92.63) U/L, (1 004.25±65.05) U/L)] and ALT [(1 172.51±180.31) U/L, (583.50±164.75) U/L] levels were increased in IRI group and IL-22+ IRI group (AST: F=293.62; ALT: F=30.33, P<0.05). The levels of MDA in IRI group and IL-22+ IRI group [(1.72±0.12) μmol/mg, (0.98±0.05) μmol/mg] in liver tissue were higher than those in Sham group (0.58±0.14) μmol/mg protein ( F=186.73, P<0.05), and the expression of p-STAT3, Nrf2 and HO-1 was increased. SOD level in IRI group (28.51±3.85) U/mg was lower than that in Sham group (70.25±5.64) U/mg protein ( F=203.41, P<0.05). Compared with IRI group, serum AST and ALT levels in IL-22+ IRI group were decreased, SOD activity in liver tissue was increased, MDA level was decreased, and p-STAT3, Nrf2 and HO-1 expression was increased (all P<0.05). Conclusion:IL-22 could alleviate liver IRI in rats, and the mechanism may be related to the activation of STAT3 and Nrf2/HO-1 signaling pathway and anti-oxidative stress.

12.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-939793

RESUMO

BACKGROUND@#Corona virus disease 2019 (COVID-19) has spread around the world since its outbreak, and there is no ascertained effective drug up to now. Lianhua Qingwen (LHQW) has been widely used in China and overseas Chinese, which had some advantages in the treatment of COVID-19.@*OBJECTIVE@#To evaluate the efficacy and safety of LHQW for COVID-19 by conducting a systematic review with meta-analysis.@*METHODS@#A comprehensive literature search was conducted in 12 electronic databases from their establishment to October 30, 2021. Note Express 3.2.0 was used for screening of trials, and the data was independently extracted in duplicate by 2 researchers. The risk of bias of randomized controlled trials (RCTs) and retrospective studies were assessed by using the Cochrane collaboration tool and Newcastle Ottawa Scale, respectively, followed by data analysis using RevMan 5.3. The RCTs or retrospective studies to treat COVID-19 using LHQW were included. The intervention measures in the experimental group were LHQW alone or combined with chemical drugs (LCWC), and that in the control group were chemical drugs (CDs). Outcome measures included computed tomography (CT) recovery rate, disappearance rates of primary (fever, cough, fatigue), respiratory, gastrointestinal and other symptoms, exacerbation rate and adverse reaction. Subgroup analysis was conducted according to whether LHQW was combined with CDs and the different treatment methods in the control group.@*RESULTS@#Nine trials with 1,152 participants with COVID-19 were included. The CT recovery rates of LHQW and LCWC were 1.36 and 1.32 times of CDs, respectively (P<0.05). Compared with CDs, LCWC remarkably increased the disappearance rates of fever, cough, fatigue, expectoration, shortness of breath, and muscle soreness (P<0.05). LHQW also obviously decreased the exacerbation rate, which was 0.45 times of CDs alone (P<0.05). There was no obvious difference between LCWC and CDs in adverse reaction (P>0.05).@*CONCLUSIONS@#LHQW was more suitable for treating COVID-19 patients with obvious expectoration, shortness of breath and muscle soreness. LHQW had advantages in treating COVID-19 with no obvious exacerbation. (PROSPERO No. CRD42021235937).


Assuntos
Humanos , COVID-19/tratamento farmacológico , Tosse/tratamento farmacológico , Medicamentos de Ervas Chinesas/efeitos adversos , Dispneia/tratamento farmacológico , Fadiga/tratamento farmacológico , Mialgia/tratamento farmacológico
13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-965551

RESUMO

@#<b>Objective</b> To investigate the dosimetric effect of truncated regions in computed tomography (CT) images on the targets and organs at risk in volumetric modulated arc therapy (VMAT) for middle thoracic esophageal cancer. <b>Methods</b> CT images of 15 patients with middle thoracic esophageal cancer were selected. Circle masks were used to make the volume of the truncated region account for 10%, 20%, 30%, and 40% of the arm volume, and the corresponding truncated CT images were obtained. The real CT was denoted as CT0. Two radiotherapy plans were made on CT0. One plan was VMAT_1F with full arcs, and the other one was VMAT_3F with arm avoidance. The plans were transplanted to four truncated CT, respectively, and the dosimetric differences between different plans were compared using Wilcoxon signed-rank test. <b>Results</b> Compared with VMAT_1F in CT0, <i>D</i><sub>mean</sub> and <i>V</i><sub>5</sub> of the lung decreased in VMAT_3F, but <i>D</i><sub>max</sub> of the spinal cord, <i>D</i><sub>mean</sub> of the heart, and <i>V</i><sub>20</sub> of the lung increased. In VMAT_3F, there was no statistically significant difference between the dosimetric parameters in the four truncated CT and those in CT0 (all <i>P</i> > 0.05). In VMAT_1F, except for homogeneity index and <i>D</i><sub>max</sub> of the spinal cord, the dosimetric parameters in four truncated CT were significantly different from those in CT0 (<i>P</i> < 0.05). The dosimetric difference increased with the increase in truncated region-to-volume ratio. <b>Conclusion</b> Complete CT data should be collected in clinical practice, and the radiation field avoiding the truncated regionshould be set if necessary to reduce the influence of the truncated region on dosimetry.

14.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-973420

RESUMO

Surface guided radiation therapy (SGRT) is a method of radiation therapy with non-invasive and non-radiation image guidance technology, which uses continuous real-time imaging to monitor the whole course of treatment. This paper summarizes the characteristics, representative products, application in clinical research and treatment, and quality control of SGRT. This emerging technology plays an increasingly important role in delivering more precise, safe, and comfortable radiotherapy to patients.

15.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21258703

RESUMO

The determinants of severe COVID-19 in non-elderly adults are poorly understood, which limits opportunities for early intervention and treatment. Here we present novel machine learning frameworks for identifying common and rare disease-associated genetic variation, which outperform conventional approaches. By integrating single-cell multiomics profiling of human lungs to link genetic signals to cell-type-specific functions, we have discovered and validated over 1,000 risk genes underlying severe COVID-19 across 19 cell types. Identified risk genes are overexpressed in healthy lungs but relatively downregulated in severely diseased lungs. Genetic risk for severe COVID-19, within both common and rare variants, is particularly enriched in natural killer (NK) cells, which places these immune cells upstream in the pathogenesis of severe disease. Mendelian randomization indicates that failed NKG2D-mediated activation of NK cells leads to critical illness. Network analysis further links multiple pathways associated with NK cell activation, including type-I-interferon-mediated signalling, to severe COVID-19. Our rare variant model, PULSE, enables sensitive prediction of severe disease in non-elderly patients based on whole-exome sequencing; individualized predictions are accurate independent of age and sex, and are consistent across multiple populations and cohorts. Risk stratification based on exome sequencing has the potential to facilitate post-exposure prophylaxis in at-risk individuals, potentially based around augmentation of NK cell function. Overall, our study characterizes a comprehensive genetic landscape of COVID-19 severity and provides novel insights into the molecular mechanisms of severe disease, leading to new therapeutic targets and sensitive detection of at-risk individuals.

16.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-880568

RESUMO

OBJECTIVE@#To investigate whether blood-brain barrier (BBB) served a key role in the edema-relief effect of bloodletting puncture at hand twelve Jing-well points (HTWP) in traumatic brain injury (TBI) and the potential molecular signaling pathways.@*METHODS@#Adult male Sprague-Dawley rats were assigned to the sham-operated (sham), TBI, and bloodletting puncture (bloodletting) groups (n=24 per group) using a randomized number table. The TBI model rats were induced by cortical contusion and then bloodletting puncture were performed at HTWP twice a day for 2 days. The neurological function and cerebral edema were evaluated by modified neurological severity score (mNSS), cerebral water content, magnetic resonance imaging and hematoxylin and eosin staining. Cerebral blood flow was measured by laser speckles. The protein levels of aquaporin 4 (AQP4), matrix metalloproteinases 9 (MMP9) and mitogen-activated protein kinase pathway (MAPK) signaling were detected by immunofluorescence staining and Western blot.@*RESULTS@#Compared with TBI group, bloodletting puncture improved neurological function at 24 and 48 h, alleviated cerebral edema at 48 h, and reduced the permeability of BBB induced by TBI (all P<0.05). The AQP4 and MMP9 which would disrupt the integrity of BBB were downregulated by bloodletting puncture (P<0.05 or P<0.01). In addition, the extracellular signal-regulated kinase (ERK) and p38 signaling pathways were inhibited by bloodletting puncture (P<0.05).@*CONCLUSIONS@#Bloodletting puncture at HTWP might play a significant role in protecting BBB through regulating the expressions of MMP9 and AQP4 as well as corresponding regulatory upstream ERK and p38 signaling pathways. Therefore, bloodletting puncture at HTWP may be a promising therapeutic strategy for TBI-induced cerebral edema.

17.
J Surg Oncol ; 122(4): 817, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38031369

RESUMO

Long-term outcomes of 530 esophageal squamous cell carcinoma patients with minimally invasive Ivor Lewis esophagectomy. J Surg Oncol. 2018; 117:957-969. https://doi.org/10.1002/jso.24997 The above article, published online on May 30, 2018 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors and the Journal Editor in Chief Dr. Stephen Sener and Wiley Periodicals, Inc. The retraction has been agreed following concerns raised that the number of patients operated on was considerably lower than the number of patients reported in the article. When asked to provide documentary evidence of the operations performed, the authors confirmed the reported discrepancy and requested to retract their article.

18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-867126

RESUMO

Objective:To investigate the characteristics of serum cytokine IL-4 and IFN- γ levels in patients with chronic insomnia with mild cognitive impairment (MCI), and to further explore the relationship between cognitive function and IL-4 and IFN-γ in patients with chronic insomnia.Methods:Sixty-two patients with chronic insomnia were divided into MCI group( n=30) and non-MCI group( n=32) according to the scores of Montreal cognitive assessment(MoCA), mini-mental state examination(MMSE) score and chief complaint of cognitive decline. Pittsburgh sleep quality index(PSQI), Hamilton depression scale(HAMD 24) and Hamilton anxiety scale 14 item(HAMA 14) were evaluated. Serum IL-4 and IFN-γ were detected by flow fluorescence, correlation analysis and regression analysis were carried out. Results:The levels of IL-4 and IFN-γ in MCI group were significantly lower than those in non-MCI group (IL-4: 0.875(0.143, 1.655)μg/L, 1.855(0.813, 2.723)μg/L; IFN-γ: 0.450(0.173, 1.163)μg/L, 1.160(0.483, 3.075)μg/L, all P<0.05). There was no significant difference in IFN- γ/IL-4, PSQI, HAMA 14 and HAMD 24 scores between MCI group and non-MCI group. IL-4 was positively correlated with the total score of MoCA( r=0.318, P<0.05), orientation( r=0.324, P<0.05)and delayed recall( r=0.368, P<0.01). The results of multivariate regression showed that IL-4 had significant effects on MCI in patients with chronic insomnia( B=2.161, OR=8.682, 95% CI=2.058~36.633, P=0.003). Conclusion:The cognitive function of chronic insomnia is closely related to serum IL-4 and IFN-γ, and serum IL-4 has a protective effect on cognition in chronic insomnia patients. Therefore, it can be speculated that cytokines may be an important pathophysiological link of cognitive change in chronic insomnia patients.

19.
Chinese Journal of Geriatrics ; (12): 1151-1154, 2020.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-869548

RESUMO

Objective:To investigate clinical significance of the detection of bone mineral density(BMD)and serum levels of vitamin D in elderly patients with Parkinson's disease(PD).Methods:Sixty elderly patients with PD(the PD group)admitted in our hospital from June 2016 to December 2018 were enrolled in this retrospective study.And 60 healthy persons confirmed by annual health check-up matched for age and sex during the same period were included as the control group.PD patients were divided into the osteoporosis group(n=23)and the non-osteoporosis group(n=37). The clinical data, bone mineral density and serum vitamin D level were compared between the two groups.Multivariate Logistic regression method was used to analyze related factors for osteoporosis in PD patients.Results:The incidences of osteoporosis and vitamin D deficiency were higher in PD group than in control group[23 cases(38.3%) vs.13 cases(21.7%)、35 cases(58.3%) vs.21 cases(35.0%), all P<0.05]. Bone mineral density and serum 25-(OH)D level were lower in PD group than in control group[(0.77±0.08)g/m 2vs.(0.83±0.09)g/m 2, (25.65±8.65)nmol/L vs.(39.80±10.74)nmol/L, t=4.381 and 8.439, P<0.05]. The age, course of disease and H-Y grade were higher and serum level of 25-(OH)D was lower in the osteoporosis group than in the control group( P<0.05). Spearman correlation analysis showed that BMD and 25-(OH)D were negatively correlated with age, course of disease and H-Y stage, respectively, and BMD was positively correlated with 25-(OH)D( r=0.396, P<0.05). Multivariate Logistic regression analysis showed that vitamin D deficiency was an independent risk factor for osteoporosis in elderly PD patients( OR=2.332, 95% CI: 1.772-8.224, P<0.01). Conclusions:The incidence of osteoporosis is high in elderly PD patients, and vitamin D deficiency is often present.Vitamin D deficiency may be an independent risk factor for osteoporosis.

20.
International Eye Science ; (12): 164-167, 2020.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-777822

RESUMO

@#AIM: To investigate the Demodex infection in patients with recurrent chalazion and the possible related factors for Demodex infection.<p>METHODS: Patients diagnosed with "chalazion" in our ocular surface and cornea department from January 2019 to May 2019 were collected. 32 eyes in group A were patients with recurrent chalazion, 30 eyes in group B were patients with primary chalazion, and 35 eyes in group C were patients without eye disease. The positive infection rate of the roots of Demodex lashes was observed by biological optical microscopy. The infection of Demodex in the roots of the eyelashes and the opening of the meibomian glands was observed by vivo laser scanning confocal microscopy.<p>RESULTS: Observations by biological optical microscope: the detection rate of Demodex in the eyelashes of group A was 78%, which was significantly higher than that of group B(57%)and group C(34%). Observations by confocal microscopy: the detection rate of Demodex in the eyelashes of group A was 88%, which was significantly higher than that of group B(67%)and group C(37%). The detection rate of Demodex in the meibomian gland opening of group A was 69%, which was significantly higher than that of group B(23%)and group C(14%).<p>CONCLUSION: The rate of Demodex infection in patients with recurrent chalazion is obviously higher. Demodex infection may be one of the pathogenic reasons for recurrent chalazion.

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