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Objective:To investigate the role of immunoglobulin-like domain-containing receptor 2 (Ildr2) in renal fibrosis induced by ischemia-reperfusion.Methods:Ildr2 knockout mice (KO group) were constructed using CRISPR/Cas9 technology, and wild-type mice were as the control group (WT group). The unilateral renal ischemia-reperfusion (UIR) model (UIR group) was constructed by clamping the left renal pedicle, and was divided into KO-UIR group and WT-UIR group after modeling. Sham operation mice (sham group) were not treated with ischemia. Serum creatinine was measured by creatinine oxidase method. Blood urea nitrogen was detected by the diacetyloxime colorimetric method. The urinary albumin level was measured by enzyme-linked immunosorbent assay, and urinary albumin/creatinine ratio was calculated. HE, PAS and MASSON staining were used to detect the infiltration of inflammatory cells and the degree of fibrosis in renal tissues. The mRNA expression levels of Ildr2, kidney injury-associated molecules neutrophil gelatinase-associated lipocalin ( NGAL) and kidney injury molecule-1 ( KIM-1), fibrosis markers typeⅠcollagen α 1 ( Col1α1), fibronectin 1 ( Fn1), α-smooth muscle actin ( α-SMA) and connective tissue growth factor ( CTGF), as well as inflammation-related molecules macrophage marker F4/80 and monocyte chemoattractant protein-1 ( MCP-1) were detected by real time quantitative PCR (qRT-PCR). The protein levels of Ildr2, α-SMA and Col1α1 were detected by immunofluorescence and Western blotting. Results:(1) qRT-PCR and Western blotting showed that the expression levels of Ildr2 mRNA and protein in UIR group were significantly lower than those in sham group (both P<0.05). (2) There were no significant differences in body weight, serum creatinine, blood urea nitrogen, total cholesterol, low density lipoprotein, high density lipoprotein and triglyceride between KO group and WT group (all P>0.05). qRT-PCR results showed that there were no significant differences in the mRNA expression levels of NGAL, KIM-1, α-SMA, Col1α1, CTGF, Fn1, MCP-1 and F4/80 between KO group and WT group (all P>0.05). Histological staining showed no abnormal inflammatory cell infiltration and interstitial fibrosis between KO group and WT group. (3) Compared with the WT-UIR group, serum creatinine and blood urea nitrogen in the KO-UIR group were significantly higher (both P<0.05). qRT-PCR results showed that the mRNA expression levels of NGAL, F4/80, MCP-1, Col1α1, α-SMA, and CTGF in the KO-UIR group were significantly higher than those in the WT-UIR group (all P<0.05). Immunofluorescence and Western blotting results also showed that the protein expression levels of Col1α1 and α-SMA in the KO-UIR group were significantly higher than those in the WT-UIR group (all P<0.05). Histological staining showed that, compare with WT-UIR group, KO-UIR group had more severe inflammatory infiltration and more collagen fiber deposition. Conclusion:Ildr2 knockout does not cause phenotypic changes in mice under normal physiological conditions. Ildr2 plays a regulatory role in UIR injury, and Ildr2 deletion aggravates the degree of renal fibrosis induced by UIR.
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Parkinsonism is a clinical syndrome caused by many reasons, mainly manifested as bradykinesia, stiffness, static tremor and postural instability. Common disease development patterns include occult onset, gradual development, and little natural remission. However, clinically there are some Parkinsonism that will improve, naturally alleviate or "cure", called reversible parkinsonism (RP). By searching the relevant literature, RP was classified into 12 different types: drugs induced, poisoning induced, infection induced, intracranial vascular induced, structural encephalopathy related, changes in intracranial pressure related, imbalance of internal environment induced, visceral diseases related, alcohol withdrawal related, surgery related, immunization and radiotherapy induced RP. This article aims to provide clinicians with more ideas for the clinical diagnosis and treatment of parkinsonism, so as to promote clinicians to make reasonable identification and diagnosis and treatment of parkinsonism as soon as possible.
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Objective:To explore the efficiency of MR psychoradiology examination in screening and classification of psychiatric disorders as well as its potential clinical application.Methods:Retrospective study was conducted for 144 patients with MR psychoradiology examination, who were diagnosed mental disorders based on International Statistical Classification of Diseases and Related Health Problems Tenth Revision (ICD-10) from September 2018 to July 2020 in West China Hospital of Sichuan University. As our previous studies, imaging diagnostic models were constructed based on gray matter volume (GMV) analysis for four kinds of psychiatric disorders, including depression, anxiety disorder, bipolar disorder and schizophrenia. For 120 patients with psychiatric disorders, the GMV change pattern of brain regions was detected and subtyped by MR psychoradiology examination with 50% similarity threshold of the above imaging diagnostic models. The diagnostic efficiency of MR psychoradiology examination was evaluated with references of clinical diagnose. For 24 patients with dementia, brain atrophy was additionally measured by conventional MR examination and MR psychoradiology examination respectively.Results:The sensitivity, specificity, Youden index and accuracy of MR psychoradiology in identifying the four psychiatric disorders were 86.6% (84/97), 69.6% (16/23), 0.56 and 83.3% (100/120), including depression [77.8% (28/36), 69.0% (58/84), 0.47, 71.7% (86/120)], schizophrenia [58.8% (10/17), 91.3% (94/103), 0.50, 86.7% (104/120)], bipolar disorder [42.1% (8/19), 96.0% (97/101), 0.38, 87.5% (105/120)] and anxiety disorder [24.0% (6/25), 100% (95/95), 0.24, 84.2% (101/120)]. As for 24 patients with dementia, 58.3% (14/24) were detected with brain atrophy by conventional MR examination, while 91.7% (22/24) were detected by MR psychoradiology examination.Conclusions:MR psychoradiology can detect the subtle brain structural abnormalities of patients with mental disorders. Although it can′t be used as an independent biomarker for disease diagnosis till now, it is of great help in improving the accuracy and objectivity of diagnosis.
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Small cell lung cancer (SCLC) is a highly aggressive and fatal malignant tumor. It has the characteristics of complex etiology, low differentiation, high malignancy, fast growth, strong invasiveness, early metastasis and acquired drug resistance, resulting in poor prognosis. In recent years, with the gradual deepening understanding on the molecular mechanism of SCLC and multi-omics data, it is proposed that molecular typing can be carried out according to the differential expression of key transcription factors, including SCLC-A, SCLC-N, SCLC-P and SCLC-I subtypes. Molecular typing of SCLC and its clinical application will help doctors to further optimize the detailed diagnosis and treatment plan of SCLC patients, so as to prolong the survival time and improve the quality of life of patients. .
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Humanos , Neoplasias Pulmonares/genética , Tipificación Molecular , Calidad de Vida , Carcinoma Pulmonar de Células Pequeñas/genética , Factores de TranscripciónRESUMEN
Clinical scales and external devices are two important ways to quantify the severity of motor symptoms for Parkinson′s disease (PD). As one representative of scales, the Unified Parkinson′s Disease Rating Scale is considered the "gold standard" in the comprehensive assessment of PD. External devices are divided into electrophysiological and mechanical devices based on the type of sensors. Both sides can monitor the PD motor symptoms objectively. Currently, numerous and ununified parameters of devices make the clinical quantification of PD symptoms still rely on scales. This article reviewed the progress on quantitative assessments of motor symptoms for Parkinson′s disease.
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Oral medicine and deep brain stimulation are two main treatments for Parkinson's disease (PD).But their long-term efficacies are decreasing,which limit the choice of patients in advanced stage.As a special way of sensory intervention,rhythmic cueing can improve gait parameters,reduce freezing of gait severity and improve gait-related mobility by activating the motor pathway directly,repairing internal clock,promoting internal dopamine release and improving cognitive function to maintain gait stability.Rhythmic auditory and visual cueing has a potential in PD treatment.
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Oral medicine and deep brain stimulation are two main treatments for Parkinson′s disease (PD). But their long-term efficacies are decreasing, which limit the choice of patients in advanced stage. As a special way of sensory intervention, rhythmic cueing can improve gait parameters, reduce freezing of gait severity and improve gait-related mobility by activating the motor pathway directly, repairing internal clock, promoting internal dopamine release and improving cognitive function to maintain gait stability. Rhythmic auditory and visual cueing has a potential in PD treatment.
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Maple syrup disease (MSUD) is a rare autosomal recessive disorder caused primarily by mutations of branched-chain keto acid dehydrogenase complex (BCKDC). BCKDC includes at least four pathogenic genes of BCKDHA, BCKDHB, DLD and DBT. The clinical manifestations of MSUD are complex, and the main symptoms at the early stage include difficulty in feeding, drowsiness, change in muscle tone and special urine flavor of maple syrup. As the disease progresses, convulsion, hypoglycemia, coma and systemic failure may occur. MSUD is easily missed or misdiagnosed during the neonatal period. This paper provides a review for recent progress made in research on MSUD including etiology, physiopathology, clinical manifestation, auxiliary examination and treatment, with a particular emphasis on genetic testing and treatment.