Parkinson’s disease (PD) is a complex, chronic, and progressive neurodegenerative disease that is characterized by irreversible dopaminergic neuronal loss in the substantia nigra. Alpha-synuclein is normally a synaptic protein that plays a key role in PD due to pathological accumulation as oligomers or fibrils. Clustered alpha-synuclein binds to the Toll-like receptors and activates the microglia, which initiates a process that continues with pro-inflammatory cytokine production and secretion. Pro-inflammatory cytokine overproduction and secretion induce cell death and accelerate PD progression. Microglia are found in a resting state in physiological conditions. Microglia became activated by stimulating Toll-like receptors on it under pathological conditions, such as alpha-synuclein aggregation, environmental toxins, or oxidative stress. The interaction between Toll-like receptors and its downstream pathway triggers an activation series, leads to nuclear factor-kappa B activation, initiates the inflammasome formation, and increases cytokine levels. This consecutive inflammatory process leads to dopaminergic cell damage and cell death. Microglia become overactive in response to chronic inflammation, which is observed in PD and causes excessive cytotoxic factor production, such as reactive oxidase, nitric oxide, and tumor necrosis factor-alpha. This inflammatory process contributes to the exacerbation of pathology by triggering neuronal damage or death. Current treatments, such as dopaminergic agonists, anticholinergics, or monoamine oxidase inhibitors alleviate PD symptoms, but they can not stop the disease progression. Finding a radical treatment option or stopping the progression is essential when considering that PD is the second most reported neurodegenerative disorder. Many cytokines are released during inflammation, and they can start the phagocytic process, which caused the degradation of infected cells along with healthy ones. Therefore, targeting the pathological mechanisms, such as microglial activation, mitochondrial dysfunction, and oxidative stress, that should be involved in the treatment program is important. Neuroinflammation is one of the key factors involved in PD pathogenesis as well as alpha-synuclein accumulation, synaptic dysfunction, or dopaminergic neuronal loss, especially in the substantia nigra. Therefore, evaluating the therapeutic efficiency of the mechanisms is important, such as microglial activation and nuclear factor-kappa B pathway or inflammasome formation inhibition, and cytokine release interruption against neuroinflammation may create new treatment possibilities for PD. This study examined the pathological relation between PD and neuroinflammation, and targeting neuroinflammation as an opportunity for PD treatments, such as Toll-like receptor antagonists, NOD-like receptor family pyrin domain containing-3 inflammasome inhibitors, cytokine inhibitors, peroxisome proliferator-activated receptor-γ agonists, reactive oxygen species inhibitors, and nonsteroidal anti-inflammatory drugs.

Aims:To evaluate the clinical, pathological, and genetic features of patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD).Methods:Thirty-one patients with RR-MADD admitted to our hospital from January 2005 to November 2020 were enrolled, and their clinical data were collected. Pathological characteristics of the muscle tissue and possible pathogenic gene mutations were analyzed.Results:The most common clinical features in all patients were symmetrical proximal muscle weakness. Laboratory examination revealed elevated levels of creatine kinase, homocysteine, and uric acid, acylcarnitines, and organic acid. The muscle biopsy revealed typical pathological changes like lipid deposition. Genetic analysis identified ETFDH mutations in 29 patients, among which one had homozygotes, 19 had compound heterozygotes, 7 had heterozygous mutations, and 2 had heterozygous mutations of both ETFDH and ETFA. Two patients had no pathogenic gene mutations. All patients were treated with riboflavin, and their symptoms improved, which was consistent with the diagnosis of RR-MADD.Conclusion:The clinical manifestations and genetic test results of patients with RR-MADD are heterogeneous. Therefore, a comprehensive analysis of clinical, pathological, and genetic testing is essential for the early diagnosis of RR-MADD.

A 29-year-old woman diagnosed with chronic sinusitis was referred to the ENT department of our hospital due to repeated nasal discharge without obvious incentives.Her vital signs were stable, and she had no other clinical symptoms.Two previous cardiac echocardiograms revealed no cardiovascular system diseases.In addition, the patient's medical history, physical examination, and relevant medical test verification did not reveal any other congenital anomalies.Noncontrast computed tomography (CT) revealed an abnormally tortuous aortic arch with local dilation.An emergency bedside ultrasound revealed that the highly tortuous aortic arch was accompanied by local cystic dilation.The patient was finally diagnosed with an aortic arch malformation with an aneurysm (Type D) (Figure 1a, suprasternal notch view; Videos 1 and 2).To confirm the diagnosis, emergency CT angiography was performed, which revealed that the cervical aortic arch had an aortic arch aneurysm and anomalous expansion of both the innominate artery and proximal right subclavian artery (Figure 1b; Video 3) along with atherosclerotic plaques of the descending thoracic aorta.Thereafter, cardiothoracic surgery was performed.During the operation, the aortic arch structure was found to be very tortuous with local expansion and aneurysm formation (Figure 1c).At present, the patient's condition is stable after artificial vessel placement (Figure 1d), and her outcome is under follow-up.

Background:MiR-196a is particularly noticeable in the development of liver cancer. However, the rapid degradation by ribonuclease (RNase) imposes a limit on the miRNA gene therapy applications.Aims:To design a novel gene-targeting nano system for liver cancer treatment.Study Design:Cell culture study and animal experimentation.Methods:Deacetylated (DEAC)-poly-N-acetylglucosamine (PNAG)-folic acid (FA) was prepared via ethyl (dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide reaction, and miR-196a inhibitor (miR-196a I)/DEAC-PNAG-FA was prepared through self-assembly. The characterization and nucleic acid protection of the self-assembly system were also determined. The biological function and related mechanism of the prepared system were studied at cellular and molecular levels. Mice were established as a xenotransplantation model to evaluate the anticancer capacity of miR-196a I/DEAC-PNAG-FA in vivo.Results:The morphology of miR-196a I/DEAC-PNAG-FA was uniform, and its particle size was approximately 70–100 nm. A nanocarrier with an N/P ratio of 200:1 can maximize the nucleic acid carrying capacity of the self-assembly system. The nanosystem can protect miRNA from RNase degradation and could be internalized rapidly within 4 h. The self-assembly system significantly enhanced the apoptosis-inducing effect of miR-196a I on HepG2 cells (P = 0.003). Molecular biological analyses confirmed that the apoptosis-inducing effect of the nanosystem was due to the inhibition of miR-196a gene expression in HepG2 cells, which upregulate the expression of pro-apoptotic proteins FOXO1 (P < 0.001), Bax (P < 0.001), Ki67 (P < 0.001), and proliferating cell nuclear antigen (P < 0.001), and inhibit the expression of apoptosis inhibitory protein Bcl-2 (P < 0.001). Moreover, compared with free miR-196a inhibitor or miR-196a I/DEAC-PNAG, miR-196a I/DEAC-PNAG-FA can more effectively inhibit tumor growth in vivo (P = 0.026).Conclusion:The newly prepared self-assembly targeting system can effectively induce apoptosis and abrogate tumor growth, which may open a new approach for liver cancer treatment.

Background:Nck1 is an important molecule that participates in many cellular processes, including neurite outgrowth, synaptic plasticity, and apoptosis. However, the expression and function of Nck1 in the spinal cord and spinal cord injury remain unknown.Aims:To investigate the role of Nck1 in spinal cord injury.Study Design:Animal experimentation.Methods:Adult Sprague–Dawley rats were used to establish an acute spinal cord injury model. Double immunofluorescence staining, Western blot, and quantitative reverse transcription polymerase chain reaction analysis were used to investigate the distribution, cellular localization, and expression of Nck1 in spinal cord injury processes. Short interfering RNA was used to silence Nck1 expression in VSC4.1 cells. The Shapiro–Wilk test was used for the normality distribution analysis; the Student’s unpaired t-test, 1-way analysis of variance followed by post hoc Tukey’s test were used for data analysis. Finally, RNA sequencing technology and gene ontology analysis were used to analyze the changes in Nck1-associated genes expression after spinal cord injury.Results:Colabeled staining demonstrated that Nck1 was especially distributed in neurons. Western blot, quantitative reverse transcription polymerase chain reaction, and statistical analysis revealed that Nck1 expression reduced to the lowest levels at 1 day after nerve injury, and slowly increased to a stable level in 21 days (P < .05). Nck1-specific short interfering RNA transfection significantly reduced cell viability and neurite development in neurons. Bioinformatic analysis indicated that Nck1 participates in multiple pathological processes of spinal cord injury, and many Nck1-associated genes exhibited differential expression levels.Conclusion:Nck1 is a vital protein in spinal cord injury processes and, therefore, further studies should be conducted to explore its potential functions and molecular mechanisms in spinal cord injury repair.

The new scientific developments and technological opportunities that have led to significant changes all build up the digital era. In medicine, the use of new technologies in patient diagnosis and treatment processes has opened new horizons for physicians and patients. As considering for the medical training, 3-dimensional modeling opportunities, virtual reality, augmented reality, and various simulators offered by the new technologies of the digital era have become a new hope. The 3-dimensional scanning and modeling, 3-dimensional medical printing, virtual reality technologies applications and simulators in urology are very recent and valuable. Besides, the exoscope-assisted 3-dimensional open surgery provides high-resolution 3-dimensional images to surgeons with high comfort as compared with old-fashioned operating microscopes. New modalities that tried to be integrated in robotic surgery are 3-dimensional reconstruction, usage of indocyanine green, augmented reality, contrast ultrasound, haptic feedback, and availability of single port. Some new companies announced their new robotic systems in the market. The use of these new technological applications during medical training, especially at the beginning of the education curve for various surgical interventions, may be beneficial in terms of reducing possible complications that may be encountered due to inexperience at the beginning of the education process and increasing patient safety. Urology will also stay at the futuristic approach in medicine, while 3-dimensional technologies used more widely in this field.

Background: Maturity-onset diabetes of the young (MODY) is a rare monogenic type of diabetes, and accounts for 2-5% of all diabetes cases. An early age of onset, a family history supporting autosomal-dominant inheritance, insulin resistance, and the absence of autoimmunity are the major characteristics of MODY. However, genetic testing is crucial for diagnosis.Aims: To investigate the 7 MODY-related genes and clinical findings of patients with a preliminary clinical diagnosis of MODY.Study Design: Retrospective cross-sectional study.Methods: In this study, 7 genes (KCNJ11, ABCC8, INS, GCK, HNF4A, HNF1A, and HNF1B) related to MODY were screened via targeted sequencing in 182 cases with a confirmed pre-diagnosis of MODY. The clinical characteristics of the patients were evaluated retrospectively.Results: A total of 182 patients, 48% of whom were women, between the ages of 18-62 were included in the study. In 30 cases (16.4%), 28 different pathogenic variations were found, of which 20 were previously reported and 8 were novel variations segregated by disease within the family. Pathogenic variations were detected in the following genes in order of mutation frequency; GCK, HNF1A, ABCC8, HNF4A, HNF1B and KCNJ11. Interestingly, six of the 30 cases (20%) carried a pathogenic variation in the ABCC8 gene. No mutation was detected in the INS gene. A family history of vertically transmitted diabetes and elevated HbA1C at the time of diagnosis were found in 20 (66%) and 16 (52%) cases, respectively.Conclusion: In this series, 28 different pathogenic variations are ­identified, 8 of which are novel. The rate of pathogenic variation in the ABCC8 gene is unexpectedly high. Two-thirds of cases have a family history of vertically transmitted diabetes.