Novel mutation c.1210-3C > G in cis with a poly-T tract of 5T affects CFTR mRNA splicing in a Chinese patient with cystic fibrosis / 医学前沿

Cystic fibrosis (CF) is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator (CFTR). To identify the potential pathogenic mutations in a Chinese patient with CF, we conducted Sanger sequencing on the genomic DNA of the patient and his parents and detected all 27 coding exons of CFTR and their flanking intronic regions. The patient is a compound heterozygote of c.2909G > A, p.Gly970Asp in exon 18 and c.1210-3C > G in cis with a poly-T of 5T (T5) sequence, 3 bp upstream in intron 9. The splicing effect of c.1210-3C > G was verified via minigene assay in vitro, indicating that wild-type plasmid containing c.1210-3C together with T7 sequence produced a normal transcript and partial exon 10-skipping-transcript, whereas mutant plasmid containing c.1210-3G in cis with T5 sequence caused almost all mRNA to skip exon 10. Overall, c.1210-3C > G, the newly identified pathogenic mutation in our patient, in combination with T5 sequence in cis, affects the CFTR gene splicing and produces nearly no normal transcript in vitro. Moreover, this patient carries a p.Gly970Asp mutation, thus confirming the high-frequency of this mutation in Chinese patients with CF.

Entrainment of Astrocytic and Neuronal Ca2+ Population Dynamics During Information Processing of Working Memory in Mice / 神经科学通报·英文版

Astrocytes are increasingly recognized to play an active role in learning and memory, but whether neural inputs can trigger event-specific astrocytic Ca2+ dynamics in real time to participate in working memory remains unclear due to the difficulties in directly monitoring astrocytic Ca2+ dynamics in animals performing tasks. Here, using fiber photometry, we showed that population astrocytic Ca2+ dynamics in the hippocampus were gated by sensory inputs (centered at the turning point of the T-maze) and modified by the reward delivery during the encoding and retrieval phases. Notably, there was a strong inter-locked and antagonistic relationship between the astrocytic and neuronal Ca2+ dynamics with a 3-s phase difference. Furthermore, there was a robust synchronization of astrocytic Ca2+ at the population level among the hippocampus, medial prefrontal cortex, and striatum. The inter-locked, bidirectional communication between astrocytes and neurons at the population level may contribute to the modulation of information processing in working memory.

Case report of neurofibromatosis type 1 combined with primary ciliary dyskinesia / 医学前沿

Neurofibromatosis (NF) is a genetic disease in which the lungs are rarely involved. However, in NF cases with lung involvement, chest computed tomography may show bilateral basal reticulations, apical bullae, and cysts without bronchiectasis. Herein, we report a patient diagnosed with NF on the basis of the results of genetic testing who presented with early-onset wet cough and bronchiectasis. Considering the differential diagnosis of bronchiectasis combined with his early-onset wet cough, sinusitis, and sperm quality decline, we considered the possibility of primary ciliary dyskinesia (PCD). Further electron microscopy analysis of cilia and identification of homozygous mutations in the RSPH4A gene confirmed the diagnosis of PCD. Therefore, for patients with NF, when an image change exists in the lungs that does not correspond to NF, the possibility of other diagnoses, including PCD, must be considered.

Applied anatomy of the compression of the proper plantar digital nerves of the medial great toe / 中华显微外科杂志

Objective To identify the routes and branches of the proper plantar digital nerves(PPDN) in the medial of the great toe and its adjoining relationship among the surrounding fascia tissues and organs,which was expected to provide accurate localization of the nerve impingement and possible relevant of anatomical basis for the treatment of nerve entrapment in clinical utility.Methods From December,2016 to January,2019,a total of 54 formalin fixed feet were collected.Fifty of them were performed conventional anatomical procedure,the other 4 were prepared with sectional anatomical technique.The seats and branches of the PPDN in the medial of the great toe were observed;The width and thickness of the nerve were measured at the first metatarpophalangeal joint(FMPJ),along with its proximal and distal sides 0.5 cm.The origin and origin of fascia were observed by foot dissection.Masson staining was used to observe the tissue changes of the nerves in the FMPJ.Results The PPDN of the medial great toe run between the flexor pollicis longus tendon and the abductor pollicis tendon at the proximal,issued (4.21±0.12) final branches.And governed the sensation of the medial half of the great toe.The width of the nerve at the FMPJ was (3.50±0.09) mm,which was significantly increased compared with that of the near [(1.58±0.04) mm] and far [(1.56± 0.03) mm] from the joint.The difference was statistically significant (P＜0.05);The thickness of the nerve in the proximal segment was (0.83±0.04) mm,and that in the distal segment was (0.82±0.03) mm.Compared with that in the FMPJ [(0.67±0.02) mm],the difference was statistically significant (P＜0.05).A deep fascia was observed on the superficial surface of the PPDN at medial great toe,which was stretched between the tendon sheath of the flexor pollicis longus tendon and the tendon of the abductor pollicis muscle.Masson staining showed obvious proliferation of nerve outer mem brane fibers at the metatarpophalangeal joint,the number of nerve fiber bundles increased,and obvious thickening of nerve fiber bundles and nerve fascia.Conclusion Long-term compression can lead to thickening of the epineurium and perineurium,and the superficial fascia is an important factor of thumb pain and numbness caused by the compression of the PPDN at medial of the great toe.

Applied anatomy of the first plantar lumbrical muscle / 中华显微外科杂志

Objective To investigate the anatomical structure of the first plantar lumbrical muscle in the foot and to measure the relevant data which could provide anatomical basis for repairing thumb and finger defects with the transplantation of toes accompanied with the first lumbrical muscle,and to explore the marphological function of the first lumbrical muscle of the foot.Methods From March,2016 to January,2018,a systematic and detailed dissection of the 50 formalin-fixed feet was performed to observe the exact position of the starting and ending points of the first lumbrical muscle,and a Vernier caloper was used to measure the relevant record data.Results The first lumbrical muscle originates from the medial portion of the flexor digitorum lungus tendon of the second toe,and the length of the ventral muscle was [55.87±8.67(79.30-41.16] mm.There were 2 endpoints in the tendon.The first one was in the medial tubercle of the proximal phalanges.The second one was aponeurosis of the dorsal toe and the tendon was divided into proximal and distal segments with the medial tubercle as the mark point.The length of the proximal segment was [15.34±4.81(5.52-25.18] mm,the width of the proximal segment was [2.31±1.12(3.28-1.21)] mm,the thickness was [0.44±0.14(0.28-0.68)] mm;the length of the distal segment was [11.51±4.06(3.46-14.90)] mm,the width was [6.10±1.44(9.36-3.70)] mm,and the thickness was [0.18±0.09(1.10-0.38)] mm.The length and thickness of the proximal segment was signifantly larger than those of the distal segment (P＜0.05).Conclusion The first lumbrical muscle has the function of maintaining the balance and stability of both the toe and the arch during movement,flexuring the metatarsophalangeal joint,extending the interosseous joint of the extensor phalangeal,adducting the second toe;also the function of preventing the second toe from pronation during foots' movement.