Study of pathogenic genes in a pedigree with familial dilated cardiomyopathy

BACKGROUND Dilated cardiomyopathy(DCM)is a genetically heterogeneous cardiac disorder characterized by left ventricular dilation and contractile dysfunction.The substantial genetic heterogeneity evident in patients with DCM contributes to variable disease severity and complicates overall prognosis,which can be very poor.AIM To identify pathogenic genes in DCM through pedigree analysis.METHODS Our research team identified a patient with DCM in the clinic.Through invest-igation,we found that the family of this patient has a typical DCM pedigree.High-throughput sequencing technology,next-generation sequencing,was used to sequence the whole exomes of seven samples in the pedigree.RESULTS A novel and potentially pathogenic gene mutation-ANK2p.F3067L-was discovered.The mutation was completely consistent with the clinical information for this DCM pedigree.Sanger sequencing was used to further verify the locus of the mutation in pedigree samples.These results were consistent with those of high-throughput sequencing.CONCLUSIONS ANK2p.F3067L is considered a novel and potentially pathogenic gene mutation in DCM.

Transplantation of autologous peripheral blood mononuclear cells in the subarachnoid space for amyotrophic lateral sclerosis:a safety analysis of 14 patients

There is a small amount of clinical data regarding the safety and feasibility of autologous peripheral blood mononuclear cell transplantation into the subarachnoid space for the treatment of amyotrophic lateral sclerosis.The objectives of this retrospective study were to assess the safety and efficacy of peripheral blood mononuclear cell transplantation in 14 amyotrophic lateral sclerosis patients to provide more objective data for future clinical trials.After stem cell mobilization and collection,autologous peripheral blood mononuclear cells（1 × 109） were isolated and directly transplanted into the subarachnoid space of amyotrophic lateral sclerosis patients.The primary outcome measure was incidence of adverse events.Secondary outcome measures were electromyography 1 week before operation and 4 weeks after operation,Functional Independence Measurement,Berg Balance Scale,and Dysarthria Assessment Scale 1 week preoperatively and 1,2,4 and 12 weeks postoperatively.There was no immediate or delayed transplant-related cytotoxicity.The number of leukocytes,serum alanine aminotransferase and creatinine levels,and body temperature were within the normal ranges.Radiographic evaluation showed no serious transplant-related adverse events.Muscle strength grade,results of Functional Independence Measurement,Berg Balance Scale,and Dysarthria Assessment Scale were not significantly different before and after treatment.These findings suggest that peripheral blood mononuclear cell transplantation into the subarachnoid space for the treatment of amyotrophic lateral sclerosis is safe,but its therapeutic effect is not remarkable.Thus,a large-sample investigation is needed to assess its efficacy further.

The sensitivity difference between the glans penis and penile shaft in primary premature ejaculation

The penis is a vital organ of perception that transmits perceived signals to ejaculation-related centers.The penis consists of the glans penis and penile shaft,which differ considerably in both histology and innervation.This paper aims to investigate whether the glans penis or the penile shaft is the main source of sensory signals from the penis and whether penile hypersensitivity affects the whole organ or only part of it.The thresholds,latencies,and amplitudes of somatosensory evoked potentials(SSEPs)were recorded in 290 individuals with primary premature ejaculation using the glans penis and penile shaft as the sensory areas.The thresholds,latencies,and amplitudes of SSEPs from the glans penis and penile shaft in patients were significantly different(all P<0.0001).The latency of the glans penis or penile shaft was shorter than average(indicating hypersensitivity)in 141(48.6%)cases,of which 50(35.5%)cases were sensitive in both the glans penis and penile shaft,14(9.9%)cases were sensitive in the glans penis only,and 77(54.6%)cases were sensitive in the penile shaft only(P<0.0001).There are statistical differences in the signals perceived through the glans penis and the penile shaft.Penile hypersensitivity does not necessarily mean that the whole penis is hypersensitive.We classify penile hypersensitivity into three categories,namely,glans penis,penile shaft,and whole-penis hypersensitivity,and we propose the new concept of penile hypersensitive zone.

An integrated supramolecular fungicide nanoplatform based on pH-sensitive metal–organic frameworks

The construction of an integrated nanoplatform with controlled fungicide delivery features in the specific microenvironment produced by fungal pathogens is a highly desirable strategy to improve the utilization of fungicides. Herein, we report a supramolecular fungicide delivery system based on benzimidazolemodified NH_(2)-MIL-101(Fe) metal–organic frameworks(B-MIL-101(Fe) MOFs) as carriers loaded with osthole(OS), and β-cyclodextrin(β-CD) as nanovalves to form β-CD@B-MIL-101(Fe)-OS. The nanoplatform can release the loaded OS for fungus control through self-degradation of the MOFs skeleton in an oxalic acid microenvironment produced by Botrytis cinerea. The experimental results exhibit that the constructed supramolecular fungicide delivery system could effectively inhibit mycelial growth and protect the tomatoes from infection by B. cinerea during the ripening stage. This strategy constructs a facile and integrated supramolecular drug delivery system for B. cinerea control and opens up a new avenue for the sustainable development of modern agriculture.