A case report on multiple acyl-CoA dehydrogenase deficiency with severe myopathy and osteoporosis.

A 35-year-old male patient presented fluctuating bilateral lower extremity weakness for 3 years. Physical examination showed grade 4 proximal muscle weakness in both lower extremities and grade 5 distal muscle weakness. Laboratory data revealed elevated creatine kinase, triglycerides, and cholesterol. Muscle pathology showed deposition of lipid droplet under the sarcolemma. Bone densitometry indicated severe osteoporosis. Next-generation sequencing revealed a pathogenic mutation in the ETFDH gene. The patient was diagnosed with late-onset multiple acyl-CoA dehydrogenase deficiency. After riboflavin treatment, symptoms of the patient were relieved, physical endurance was restored, and bone mineral density was improved.

The Role of G3BP1 Gene Mediates P38 MAPK/JNK Pathway in Testicular Spermatogenic Dysfunction Caused by Cyfluthrin.

In recent years, male infertility has received global attention and seriously affected the quality of human fertility, and pyrethroids (type II pyrethroids), as recognized environmental endocrine disruptors, may threaten male reproductive health. Therefore, in this study, we established an in vivo model for the development of testicular and germ cell toxicity induced by cyfluthrin and explored the role and mechanism of the G3BP1 gene-mediated P38 MAPK/JNK pathway in testicular and germ cell damage caused by cyfluthrin to find early and sensitive indicators and new therapeutic targets for the development of testicular damage. Firstly, 40 male Wistar rats (about 260 g) were divided into a control group (corn oil), low dose group (6.25 mg/kg), middle dose group (12.5 mg/kg) and high dose group (25 mg/kg). The rats were anesthetized and executed after 28 days of poisoning on alternate days. Then, HE staining, transmission electron microscopy, ELISA, q-PCR, Western blot, immunohistochemistry, double-immunofluorescence and TUNEL were used to observe the pathology, androgen levels, oxidative damage and altered expression of the key factors of the G3BP1 and MAPK pathways in rat testes. The results showed that, compared with the control group, the testicular tissue and spermatocytes were superficially damaged with an increasing dose of cyfluthrin; furthermore, it could interfere with the normal secretion of the hypothalamic-pituitary-gonadal axis (serum GnRH, FSH, T and LH levels) and cause hypergonadal dysfunction. A dose-dependent increase in MDA and a dose-dependent decrease in T-AOC indicated that the oxidative-antioxidative homeostatic balance was disrupted. The Western blot and qPCR analysis revealed that G3BP1, p-JNK1/2/3, P38 MAPK, p-ERK, COX1 and COX4 proteins and mRNA expression were decreased, and p-JNK1/2/3, p-P38MAPK, caspase 3/8/9 proteins and mRNA expression were significantly increased. The double-immunofluorescence and immunohistochemistry results showed that the protein expression of G3BP1 decreased with an increasing dose of staining, while the expression of JNK1/2/3 and P38 MAPK were increased significantly. The positive expressions of G3BP1 were mainly located in the testicular germinal epithelium and germ cell layer, and the positive expressions of JNK1/2/3 were mainly located in the testicular germinal epithelium and sperm cells, while the positive expressions of P38 MAPK were located in all levels of the germ cells and spermatozoa. Our results demonstrated that exposure to cyfluthrin caused testicular and spermatocyte damage in rats, which could cause pathomorphology, altered androgen levels and a decreased antioxidant capacity. When the intracellular antioxidant capacity was impaired, G3BP1 expression and activity were inhibited, causing activation of the P38 MAPK/JNK pathway and activation of the intracellular apoptotic pathway, which, in turn, led to germ cell apoptosis.

Ankylosing spondylitis with Kikuchi-Fujimoto disease: A case report with literature review.

We present the case of a patient diagnosed with ankylosing spondylitis (AS) along with Kikuchi-Fujimoto disease (KFD), possibly triggered by infection or autoimmunity. Both AS and KFD involved a similar immune pathway. Hence, clinicians should consider the possibility of KFD when lymphadenopathy is observed, especially in patients with infection or underlying autoimmune diseases.

Case report: Successful treatment with tofacitinib and colchicine in a patient with Schnitzler syndrome.

We report a case of late-onset Schnitzler syndrome successfully treated with Janus-activated kinase (JAK) inhibitors and colchicine. Schnitzler syndrome should be considered for recurrent chronic urticaria when accompanied by fever, fatigue, rapid weight loss, and poor response to antihistamine treatment. Skin biopsy, bone marrow biopsy, and electrophoresis help confirm the diagnosis. Early diagnosis and treatment can lead to complete resolution of symptoms. Besides interleukin (IL)-1 and IL-6 inhibitors, JAK inhibitors and colchicine may be considered as other choices of treatment.

The role of stimulator of interferon genes-mediated AMPK/mTOR/P70S6K autophagy pathway in cyfluthrin-induced testicular injury.

Cyfluthrin is widely used in the field of sanitary pest control by its wide insecticidal spectrum, high efficiency and low toxicity, low residue, and good biodegradability. But, as a double-edged sword, a large amount of cyfluthrin remains are still in the environment. The residual cyfluthrin is absorbed into the food chain through vegetation and then poses a risk to soil organisms and human health. Several studies have suggested that cyfluthrin is one of the main factors causing testicular damage, but the mechanism remains unclear. In this study, we established in vivo and in vitro models of testicular injury in rats and GC-2 cells exposed to cyfluthrin to explore whether stimulator of interferon genes (STING) gene mediates the regulation of AMPK/mTOR/p70S6K autophagy pathway, which lays a foundation for further study of the mechanism of testicular injury induced by cyfluthrin. The results showed that the activity of super oxide dismutase in testis decreased and the activity of malonic dialdehyde increased with the increase of concentration in vivo and in vitro. At the same time, the levels of mitochondrial damage and inflammation in the testis also increased, which further activated autophagy. In this process, the increased level of inflammation is related to the increased expression of STING gene, and AMPK/mTOR/p70S6K autophagy pathway is also involved. To sum up, cyfluthrin has certain reproductive toxicity, and long-term exposure can induce testicular cell damage. STING gene can participate in cyfluthrin-induced testicular injury through AMPK/mTOR/P70S6K autophagy pathway.

Serum Levels of Mitochondrial Fission- and Fusion-Related Genes of Coal Workers' Pneumoconiosis and Risk Factor Analysis Based on a Generalized Linear Model.

Objective: We aimed to explore the risk factors for coal workers' pneumoconiosis and to further explore the significance of mitochondrial fission and fusion factors in CWP and verify the feasibility of mitochondrial fission and fusion factors as diagnostic and therapeutic targets. Methods: The data of 168 cases were collected, and they were divided into a healthy control group (40 cases), dust exposure control group (61 cases), and CWP group (67 cases) and entered into SPSS 24.0. The statistical data were analyzed by the chi-square test or Fisher's exact probability method. The variables with statistically significant differences of the univariate analysis results were included in the generalized linear model. Test level was α = 0.05. Blood samples were collected to detect the ROS content, MDA content, and SOD activity. The mRNA expression levels of OPA1, Drp1, MFN2, Fis1, Col I, Col III, and α-SMA were determined by q-PCR. The protein expression levels of OPA1, Drp1, MFN2, Fis1, Col I, Col III, and α-SMA were detected by western blot. Results: Generalized linear regression analysis showed that lower school education, no respiratory protective measures, the working age beyond 15 years, and the type of work like coal mine drillers were the risk factors for CWP. With the aggravation of CWP, the degree of fibrosis and inflammation increased oxidative damage, increased mitochondrion division, and decreased fusion, which were more sensitive in the second and third stages of CWP. Conclusion: The results in this found that mitochondria are injured by fission and fusion in the CWP patients. Detection of the mitochondria fission and fusion factors provides the application value to evaluate the injury degree and progress of CWP and the clues for finding the real and effective screening and diagnosis biomarkers.

A novel iodine-mediated tandem cyclization-cycloaddition reaction leading to polyoxacyclic ring systems.

A novel iodine-catalyzed tandem cyclization-cycloaddition reaction of ortho-alkynyl-substituted benzaldehydes leading to polyoxacyclic ring systems has been developed, which represents a useful approach towards the synthesis of the oxabicyclo-[3.2.1]octane ring skeleton found in a variety of natural products.

Copper-catalyzed [4 + 1] cycloadditions of alpha,beta-acetylenic ketones with diazoacetates to form trisubstituted furans.

Copper-catalyzed [4 + 1] cycloaddition reaction of alpha,beta-acetylenic ketones with alpha-diazo esters offers an efficient, direct route to highly substituted furans. The reaction conditions and the scope of the process are examined, and a possible mechanism is proposed.