Alternative splicing of pre-messenger RNA (pre-mRNA) is a crucial mechanism for the diversity of the human transcriptome and proteome. Alternative splicing is a complex gene regulation process. Whole-transcriptome analysis shows that 95% of human exonic genes are alternatively spliced, involving various cis-acting elements and trans-acting factors. Any changes in any component or step may cause erroneous splicing events and lead to the occurrence of various related diseases. In addition to gene replacement therapy that directly changes the splicing results, RNA splicing modification is expected to become a new therapeutic strategy to alleviate or treat diseases by targeting and correcting abnormal pre-mRNA splicing. Splicing modification tools currently developed including RNA trans-splicing, antisense oligonucleotides, small interfering RNA, and small molecule drugs can correct abnormal splicing through different ways. This article reviews the resent progress of epigenetic regulation of pre-mRNA alternative splicing in recent years, and discusses the occurrence and regulation of alternative splicing, the types of diseases caused by related splicing defects, and the current-used tools for targeting and altering splicing. The importance of splicing modification strategies in the future treatment of human diseases is envisioned.

Objective To explore the role of somatosensory evoked potentials elicited by paraspinal stimulation in the detection of spinal cord lesions.Methods Patients with clinically suspected spinal cord lesions underwent somatosensory evoked potentials(SEPs)and spinal cord conduction velocity(SCCV)test using paraspinal stimulating method.96 patients aged 15 to 75 years old with suspected spinal cord lesions of various aetiologies were tested.36 patients had demyelinating disease of the spinal cord,26 had sub-acute combined degeneration of the spinal cord,19 had myelopathy,10 had acute myelitis,5 had spinal cord corhpression.Results Paraspinal stimulation elicited somatosensory evoked potentials were Performed on all 96 patients,68 of whom underwent spinal MRI as well.SEPs and SCCV were found abnormal in a high ratio in all kinds of spinal cord lesions ; in general,78 among the 96 patients had abnormal SEPs with a sensitivity of 81.25%.27 out of 36 with demyelinating disease of the spine had abnormal SEPs with a sensitivity of 75.00%,23 out of 26 with subacute combined degeneration of the spinal cord had abnormal SEPs with a sensitivity of 88.46%,8 out of 10 with acute myelitis had abnormal SEPs,15 patients with myelopathy having abnormal findings,all 5 patients with spinal cord compression had abnormal SEPs.42 of 68 patients undergoing MRI revealed to be abnormal,in which 35 patients also had abnormal SEPs.The other 26 patients had normal spinal MRI,in which 21 patients had abnormal SEPs.Conclusions Paraspinal stimulation somatosensory evoked potentials and spinal cord conduction velocity may objectively document the abnormalities of electrophysiology,which occurs earlier than those of anatomy and radiological finds, therefore it may detect the dysfunction of spinal cord at an early stage.It is even more useful in the detecting of the metabolic myelopathy,which can hardly be detected by MRI.This technique is simple,inexpensive, and maybe useful in the diagnosis for patients with suspected spinal cord lesions.

BACKGROUNDCubital tunnel syndrome is a well-recognized clinical condition and is the second most common peripheral compression neuropathy. This study was designed to investigate the causes of cubital tunnel syndrome by surgical means and to assess the clinical value of the neurophysiological diagnosis of cubital tunnel syndrome.

METHODSTwenty-one patients (involving a total of 22 limbs from 16 men and 5 women, aged 22 to 63, with a mean age of 49 years) with clinical symptoms and signs indicating a problem with their ulnar nerve underwent motor conduction velocity examinations at different sites along the ulnar nerve and examinations of sensory conduction velocity in the hand, before undergoing anterior transposition of the ulnar nerve.

RESULTSElectromyographic abnormalities were seen in 21 of 22 limbs [motor nerve conduction velocity (MCV) range (15.9 - 47.5) m/s, mean 32.7 m/s] who underwent motor conduction velocity examinations across the elbow segment of the ulnar nerve. Reduced velocity was observed in 13 of 22 limbs [MCV (15.7 - 59.6) m/s, mean 40.4 m/s] undergoing MCV tests in the forearms. An absent or abnormal sensory nerve action potential following stimulation was detected in the little finger of 14 of 22 limbs. The factors responsible for ulnar compression based on observations made during surgery were as follows: 15 cases involved compression by arcuate ligaments, muscle tendons, or bone hyperplasia; 2 involved fibrous adhesion; 3 involved compression by the venous plexus or a concurrent thick vein; 2 involved compression by cysts.

CONCLUSIONSFactors inducing cubital tunnel syndrome include both common factors that have been reported and rare factors, involving the venous plexus, thick veins, and cysts. Tests of motor conduction velocity at different sites along the ulnar nerve should be helpful in diagnosis cubital tunnel syndrome, especially MCV tests indicating decreased velocity across the elbow segment of the ulnar nerve.

Adult ; Cubital Tunnel Syndrome ; etiology ; physiopathology ; surgery ; Electromyography ; Evoked Potentials, Motor ; Evoked Potentials, Somatosensory ; Female ; Humans ; Male ; Middle Aged

OBJECTIVEThis study was aimed to analyze the relationship between single nucleotide polymorphisms of transforming growth factor-β1 G-800A and C-509T, interleukin-4 receptor V75I and susceptibility of CHL in adults.

METHODSPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied to analyze the expressed alleles of the selected SNP loca. The relationship between genomic polymorphisms of TGF-β1 and IL-4R and susceptibility of CHL were coupled with clinical data.

RESULTSTGF-β1G-800A and TGF-β1C-509T had obvious linkage equilibrium (D' = 0.879, r(2) = 0.83, P = 0.020). GT haplotype distribution frequencies in mixed cellularity Hodgkin lymphoma cases and control group were of 53.1% and 34.2%, respectively, with statistically significant (OR = 2.35, P = 0.000); distribution frequencies of mutant gene T/T in disease and control groups were of 38.8% and 15.3%, respectively, also with statistically significant (OR = 3.654, P = 0.000); frequencies of nodular sclerosis CHL patients with IL-4R V75I mutant gene A/A in disease and control groups were of 19.2% and 41.75%, respectively, also with statistically significant (OR = 3.156, P = 0.000).

CONCLUSIONSingle nucleotide polymorphisms of TGF-β1 G-800A, C-509T and IL-4R V75I has a significant correlation with Chinese susceptibility to classical Hodgkin lymphoma.

Adult ; Alleles ; Asian Continental Ancestry Group ; genetics ; Female ; Genotype ; Haplotypes ; Hodgkin Disease ; genetics ; pathology ; Humans ; Male ; Middle Aged ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Receptors, Interleukin-4 ; genetics ; Transforming Growth Factor beta ; genetics ; Young Adult

OBJECTIVETo observe the effects of Ganoderma lucidum spores on Cytochrome C (Cyt-C) and mitochondrial calcium in the testis of NIDDM rats.

METHODSFifty male Wistar rats were divided randomly into three groups: model, ganoderma and normal control, the first two groups injected with 2% STZ through vena caudalis, and the last one with half-and-half sodium citrate/citrate buffer solution. Two weeks after normal diet, glucose tolerance tests were performed and the rats with abnormal glucose tolerance from the model and ganoderma groups received high-fat and high-carbohydrate food, the ganoderma group given Ganoderma lucidum spores (250mg/[ kg x d] ) in addition, both for 10 weeks. Glucose tolerance tests were repeated 1 day before the end of the experiment and the rats were castrated and relevant indexes measured.

RESULTSThe NIDDM model was successfully constructed. In the model group, the levels of mitochondrial Cyt-C and mitochondrial calcium were significantly lower (P <0. 05) while that of the plasma Cyt-C was significantly higher than in the ganoderma and the control groups.

CONCLUSIONCyt-C and calcium ion are involved in the damage of the testis. Ganoderma lucidum spores can protect the testis of NIDDM rats.

Animals ; Calcium ; metabolism ; Cytochromes c ; metabolism ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetes Mellitus, Type 2 ; drug therapy ; Male ; Mitochondria ; drug effects ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Reishi ; Testis ; drug effects ; metabolism

BACKGROUNDDiabetic neuropathy is common in diabetes mellitus. The early stage of diabetic neuropathy is often symptomless and difficult to be treated. The aim of this study was to assess the correlation between the results of the sympathetic skin response (SSR) test and the development of diabetic neuropathy, and explore the use of SSR as an objective basis for the early diagnosis of diabetic neuropathy.

METHODSThe latencies and amplitudes of initiation and of the N and P waves were determined by SSR testing of the extremities of 80 diabetic patients and 30 healthy controls.

RESULTSThe latencies of initiation and of the N and P waves were significantly (P <0.001) longer in diabetic patients than in the controls, while there was no significant difference in the amplitudes (P >0.05). All but two patients (97.5%) demonstrated abnormal SSR in at least one limb.

CONCLUSIONSSSR can detect early dysfunction of the small sympathetic fibers in people affected by diabetes mellitus, and may be a useful electrophysiological test for the early diagnosis of diabetic neuropathy.

Adult ; Aged ; Diabetic Neuropathies ; diagnosis ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Reaction Time ; Skin ; innervation ; Sympathetic Nervous System ; physiology

AIMTo study the protective effects of hydroxyethylpuerarin against the injury of astrocytes induced by hydrogen peroxide (H2O2).

METHODSExperiments were performed with cells from passage 4. Plasma membrane integrity was measured by lactate dehydrogenase (LDH) release. The occurrence of apoptosis was measured by flow cytometry. The glutamate uptake of astrocytes was studied with [3H]-glutamate incorporation. Intracellular superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were assessed by automatic biochemistry analyzer.

RESULTSCompared with H2O2 injured group, the occurrence of apoptosis, levels of LDH release and intracellular MDA of astrocytes reduced in hydroxyethylpuerarin pre-treated groups, but the glutamate uptake and intracellular SOD activity of astrocytes increased.

CONCLUSIONHydroxyethylpuerarin could reduce the occurrence of apoptosis and improve neurotrophic function of astrocytes, which may be related with its antioxidant effects during oxidative stress.

Animals ; Animals, Newborn ; Antioxidants ; isolation & purification ; pharmacology ; Apoptosis ; drug effects ; Astrocytes ; cytology ; drug effects ; metabolism ; Brain ; cytology ; metabolism ; Cells, Cultured ; Glutamic Acid ; metabolism ; Hydrogen Peroxide ; toxicity ; Isoflavones ; isolation & purification ; pharmacology ; L-Lactate Dehydrogenase ; metabolism ; Malondialdehyde ; metabolism ; Neuroprotective Agents ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Pueraria ; chemistry ; Rats ; Rats, Wistar ; Superoxide Dismutase ; metabolism

Objective To investigate the changes of tight junction (TJ) protein occludin expression between the mierovascular endothelial cells of the blood-brain barrier (BBB) of rats after intracerebral hemorrhage (ICH). Methods Ninety-three male SD rats were randomly divided into normal control group and experimental group; rats of the experimental group were divided into 6 subgroups (6, 24, 48 and 72 h, and 7 and 14 d after intraeerebral hemorrhage). Rat models of intracerebral hemorrhage in the experimental group were established by autologous blood injection.Morphology of the brain tissues was detected by hematoxylin-eosin (HE) staining.The tight junctions between the microvascular endothelial cells of the BBB were sampled for ultrastructural observation using electron microcopy.Immunofluorescence and quantitative real time-PCR were used to analyze the protein and mRNA expressions of occludin,respectively. Results The brain edema was found in brain tissues around the hematoma. Necrosis and inflammatory infiltration could be found in perihematomal brain tissues and it was most obvious at 48 h after intracerebral hemorrhage. Obvious paracellular clefts were found between the adjacent endothelial cells in experimental groups. Strong expression of occludin was noted in the normal brain tissue; expression of occludin was positive 6 h after the injection and weak positive at 24, 48 and 72 h after the injection in the experimental groups.Quantitative real time-PCR showed that the mRNA expression of occludin in the experimental group was significantly reduced as compared with the normal brain tissue at 6,24,48 and 72 h after the injection with statistically significant difference (P＜0.05). Conclusion After intra-cerebral hemorrhage,as a major component of TJ of the BBB,occludin expression is down-regulated,which may be one of the most impotant molecular basis of disruption of BBB.

Objective To observe the expression of growth factors (vascular endothelial growth factor [VEGF],stromal cell-derived factor-1 [SDF-1 ],basic fibroblast growth factor [bFGF],insulin-like growth factor [IGF-1],transforming growth factor-β [TGF-β],platelet-derived growth factor [PDGF],brain derived neurotrophic factor [BDNF],glial cell line-derived neurotrophic factor [GDNF] and nerve growth factor [NGF]) in rat ischemic brain tissues after intravenous implantation of bone marrow stromal cells (BMSCs) and/or endothelial progenitor cells (EPCs). Methods Healthy adult Wistar rats were randomly divided into 4 groups:vehicle group,BMSCs transplantation group,EPCs transplantation group and BMSCs combined with EPCs transplantation group (n=20). The rats were subjected to middle cerebral artery occlusion (MCAO),and 24 h after that,they were intravenously transplanted with either 3×106 BMSCs,EPCs,BMSCs/EPCs or 1 mL physiological saline.Seven d after transplantation,real time-PCR and Western blotting were employed to detect the expressions of VEGF,SDF-1,bFGF,IGF-1,TGF-β,PDGF-BB,BDNF,GDNF and NGF. Results The mRNA expressions of bFGF,VEGF and BNDF in the BMSCs/EPCs transplantation group were significantly higher as compared with those in the other groups (P＜0.05).BMSCs transplantation group enjoyed the highest mRNA levels of NGF,GDNF and TGF-β among all the groups, significantly higher as compared with those in the other groups (P＜0.05),followed by BMSCs/EPCs transplantation group.EPCs transplantation group enjoyed the highest mRNA levels of PDGF,IGF-1 and SDF-1,significantly higher as compared with those in the other groups (P＜ 0.05), followed by BMSCs/EPCs transplantation group. Conclusion BMSCs combined with EPCs implantation can promote the functional rehabilitation in rats after focal cerebral ischemia, which provides new way for improving the transplantation success rate.

Objective To clarify the understanding of types of laboratories and manufacturers for GB 9706.1-2020 Medical electrical equipment-Part 1:General requirements for basic safety and essential performance by laboratory proficiency testing for creepage distance and electrical clearance test.Methods An operation guide was formed according to the testing program in GB 9706.1-2020,and the homogeneity and stability of the samples were evaluated according to CNAS-GL003:2018 Guidance on Evaluating the Homogenneity and Stability of Samples Used for Proficiency Testing.Robust statistic methods were used to assess the quantitative parameters of the test results of the participating laboratories according to the requirements in GB/T 28043-2019 Statistical methods for use in proficiency testing by interlaboratory comparison;the results reported by the expert laboratories were used as the specified values of the qualitative parameters.SPSS 25.0 statistical software was used for data analysis.Results All the results of the crreepage distance and electrical clearance tests met the requirements for homogeneity and stability.Of the 46 laboratories involved in,37 ones did have comprehensive satisfactory determinations while the remained 9 ones not.Conclusion Some laboratories don't behave well in understanding the standard,which have to be reformed accordingly to enhance their proficiencies.[Chinese Medical Equipment Journal,2024,45(10):54-59]