Application of knowledge distillation technology for fine segmentation of three-vessel and trachea views in fetal echocardiographic images / 中华超声影像学杂志

Objective:To explore the application value of fetal heart ultrasound image segmentation network model based on knowledge distillation technology in the fine segmentation of fetal heart ultrasound image at three-vessel and trachea (3VT) views.Methods:One thousand and three hundred fetals were retrospectively collected from Sir Run Run Shaw Hospital, Zhejiang University College of Medicine from January 2016 to December 2021, the two-dimensional grayscale ultrasound images of fetal heart at 3VT views were analyzed and then divided into training, validation, and test sets. The training and validation sets were used to construct the auxiliary diagnostic network models, and the test set was used to test the reliability of different network models (U-Net, DeepLabv3+ ). The 3VT views were collected and annotated by an experienced doctor as the reference standard. The intersection over union (IoU), pixel accuracy (PA) and Dice coefficient (Dice) were used as the 3 indexes to evaluate the segmentation accuracy, and the diagnostic efficiency of the training model was evaluated. The training model and the most commonly used segmentation models were identified, and the results were compared. A total of 101 images were randomly selected and assigned to junior doctors, AI and junior doctors assisted AI interpretation. Bland-Altman images were drawn to evaluate their consistency with the reference standard, and the results were compared.Results:The training model of knowledge distillation algorithm achieved better results than U-Net, DeepLabv3+ models on all evaluation indexes, and the average IoU, PA and Dice were 68.6%, 81.4% and 81.3%, respectively. Compared with the U-Net model and DeepLabv3+ model, more accurate segmentation boundaries were obtained by the knowledge distillation algorithm training model, and the quantitative evaluation indexes were improved. With the aid of the model, the diagnostic accuracy of junior doctors was improved.Conclusions:The knowledge distillation algorithm training model segmentation method can identify the anatomical structure of the fetal heart in the 3VT view of the fetal heart ultrasound image, and the recognition result is obviously better than other related methods, and can improve the accuracy of image recognition for doctors with low experience.

Influencing factors for the prognosis of patients with drug-induced liver injury and establishment of a nomogram model / 临床肝胆病杂志

ObjectiveTo investigate the influencing factors for the clinical outcome of patients with drug-induced liver injury （DILI）， and to establish a nomogram prediction model for validation. MethodsA retrospective analysis was performed for the general information and laboratory data of 188 patients with DILI who were admitted to Heilongjiang Provincial Hospital Affiliated to Harbin Institute of Technology from January 2017 to December 2022， and according to their clinical outcome， they were divided into good outcome group with 146 patients and poor outcome group with 42 patients. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate Logistic regression analyses were used to investigate the independent influencing factors for the clinical outcome of DILI patients. R Studio 4.1.2 software was used to establish a nomogram model， and calibration curve， receiver operating characteristic （ROC） curve， and decision curve analysis （DCA） were used to perform internal validation. ResultsThe univariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI， platelet count， cholinesterase， albumin， prothrombin time activity， IgM， and IgG were associated with adverse outcomes in patients with DILI. The multivariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI （odds ratio ［OR］=0.072， 95% confidence interval ［CI］： 0.022‍ ‍—‍ ‍0.213， P<0.001）， clinical classification （OR=0.463， 95%CI： 0.213‍ ‍—‍ ‍0.926， P=0.039）， alanine aminotransferase （OR=0.999， 95%CI： 0.998‍ ‍—‍ ‍1.000， P=0.025）， prothrombin time activity （OR=0.973， 95%CI： 0.952‍ ‍—‍ ‍0.993， P=0.011）， and IgM （OR=1.456， 95%CI： 1.082‍ ‍—‍ ‍2.021， P=0.015） were independent influencing factors for clinical outcome in patients with DILI. The nomogram prediction model was established， and after validation， the calibration curve was close to the reference curve. The area under the ROC curve was 0.829， and the DCA curve showed that the model had good net clinical benefit. ConclusionThe nomogram prediction model established in this study has good clinical calibration， discriminative ability， and application value in evaluating the clinical outcome of patients with DILI.

Erratum: Author correction to "TMEM16A inhibits angiotensin II-induced basilar artery smooth muscle cell migration in a WNK1-dependent manner" Acta Pharm Sin B 11(12) (2021) 3994-4007

[This corrects the article DOI: 10.1016/j.apsb.2021.04.013.].

Analysis of clinical, imaging and gene mutations in 2 pedigrees with hereditary spastic paraplegia type 7 / 中华神经科杂志

Objective:To analyze the clinical, imaging and genetic characteristics of 2 pedigrees with hereditary spastic paraplegia type 7 (SPG7).Methods:The clinical data of the probands and related members of 2 families hospitalized in the Department of Neurology of Henan Provincial People′s Hospital from December 2018 to December 2021 were collected. The probands and all family members were subjected to cranial MRI imaging and genetic testing, and the clinical characteristics and genetic variation of SPG7 families were compared with those reported in the literature.Results:Four patients from the 2 families were observed with adult-onset age in this group. The main manifestations were wide-base ataxic gait in 4 cases, and spastic gait in 1 case during follow-up. Pyramidal tract involvement mainly in the lower limbs were found in all cases, and dysarthria in 3 cases. MRI of 3 patients showed varying degrees of cerebellar atrophy. Genetic testing revealed compound heterozygous or homozygous variants of the SPG7 gene in the 4 patients, of which c.2062C>T and c.2176C>T were novel mutations. At present, only 5 SPG7 families have been reported in China. Among the 12 patients in all groups, 12 cases of pyramidal tract involvement, 10 cases of cerebellar ataxia, 7 cases of dysarticulation, 3 cases of cognitive impairment, 11 cases of complex hereditary spastic paraplegia, 1 case of simple hereditary spastic paraplegia, and 9 cases of cerebellar atrophy were reported. Six novel mutations have been reported in 5 families. Conclusions:SPG7 family is rarely reported in China, mainly manifested as pyramidal tract involvement combined with cerebellar ataxia, accompanied by cerebellar atrophy. SPG7 mutation is confirmed by genetic detection, and there are many novel mutations in SPG7 family in China.

Muscle MRI features of the lower extremities in patients with limb girdle muscular dystrophy type R1 / 中华神经医学杂志

Objective:To investigate the muscle MRI features of the lower extremities and correlations between MRI fatty degeneration total scores and other clinical features in limb girdle muscular dystrophy type R1 (LGMDR1) patients.Methods:Clinical data of 8 patients with LGMDR1 diagnosed by genetic examination in Department of Neurology, He'nan Provincial People's Hospital&People's Hospital of Zhengzhou University from May 2016 to November 2021 were retrospectively analyzed. Disease severity was evaluated by Gardner-Medwin and Walton (GM-W) scale. Pathological staining results of the lower limb muscles were observed; the fatty infiltration and edema of the muscles were observed by MRI T1WI and short-tau inversion recovery (STIR) sequences. Lower limb muscles were scored using Mercuri's scale. Spearman rank correlation was used to analyze the correlations of MRI fatty degeneration total scores of the lower extremities with age, age of onset, disease duration, GM-W scale scores and creatinine kinase (CK) level.Results:Of the 8 patients with LGMDR1, 7 had decreased muscle strength in the proximal lower extremity, including 4 with decreased muscle strength in the distal lower extremity at the same time. Muscular dystrophy-like pathological changes of skeletal muscles were noted. All 8 LGMDR1 patients showed different degrees of fatty infiltration in the lower extremities: at the thigh level, the adductor magnus, biceps femoris long head, semimembranes, semitendinosus and adductor longus were the most severely fatty degeneration muscles (mean scores>4), with relatively sparing of the sartorius and rectus femoris; regarding the calves, gastrocnemius medial head was the mostly involved, followed by soleus, with relative sparing of the tibialis posterior and anterior compartment. Edema-like changes (mild) were observed in 7 patients; the muscles that most frequently and relatively severely displayed edema-like changes were the gastrocnemius lateral head and quadriceps. The fatty degeneration total scores of the lower extremities were positively correlated with GM-W scale scores ( r=0.872, P=0.005) and negatively correlated with CK level ( r=-0.929, P=0.001), but not significantly correlated with age, age of onset or disease duration ( r=0.635, P=0.091; r=0.571, P=0.139; r=0.551, P=0.157). Conclusion:The lower limb muscles with severe fatty infiltration are less prone to show edema-like changes; fatty degeneration can be used to evaluate LGMDR1 progress; involvement pattern of muscle MRI of the lower extremities is helpful in diagnosing and differentially diagnosing LGMDR1.

Analysis of the clinical, pathological and genetic features of patients with myopathy-type very long chain acyl-coenzyme A dehydrogenase deficiency / 中华神经科杂志

Objective:To investigate the clinical, pathological and genetic characteristics of myopathy-type very long chain acyl-coenzyme A dehydrogenase deficiency (VLCADD).Methods:The detailed clinical data, muscle biopsy pathology and molecular results of 4 patients with genetically confirmed myopathy-type VLCADD admitted to Henan Provincial People′s Hospital and Xuanwu Hospital, Capital Medical University from June 2014 to November 2019 were retrospectively analyzed.Results:All of the 4 patients were late-onset myopathy-type VLCADD. The onset age ranged from 13 to 16 years, with a mean age of 14.5 years. The age at diagnosis ranged from 21 to 54 years, with a mean age of 42.5 years. The main clinical manifestation was repeated rhabdomyolysis, including myalgia, weakness and dark urine. Obvious somnolence was observerd in 1 patient. Muscle biopsy pathology revealed mild lipid accumulation, without vacuoles. Six ACADVL variations were detected in the 4 patients, including c.1283G>A (p.R428H), c.1532G>A (p.R511Q), c.833_835delAGA (p.K278del), c.1843C>T (p.R615 *), c.1748C>T (p.S583L) and c.1391C>T (p.T464I),among which c.1391C>T (p.T464I) was a novel variation, predicted to be likely pathogenic. Other 5 variations were reported pathogenic variations. Conclusions:Myopathy-type VLCADD is characterized by paroxysmal rhabdomyolysis and can be associated with somnolence. There is no specificity in muscle pathology. There are ACADVL variations, among which c.1391C>T is a novel variation.

Erratum: Author correction to 'TMEM16A inhibits angiotensin II-induced basilar artery smooth muscle cell migration in a WNK1-dependent manner' Acta Pharmaceutica Sinica B 11 (2021) 3994-4007

[This corrects the article DOI: 10.1016/j.apsb.2021.04.013.].

Arthroscopic treatment of scaphoid fracture nonunion with bone graft and Kirschner wire combined with screw fixation / 中国修复重建外科杂志

OBJECTIVE@#To explore the effectiveness of arthroscopic treatment of scaphoid fracture nonunion with bone graft and Kirschner wire combined with screw fixation.@*METHODS@#The clinical data of 14 patients with scaphoid fracture nonunion who met the selection criteria between February 2021 and September 2022 were retrospectively analyzed. There were 13 males and 1 female with an average age of 32 years ranging from 17 to 54 years. The time from injury to operation ranged from 6 to 15 months, with an average of 9.6 months. According to the Slade-Geissler classification of scaphoid fracture nonunion, there were 3 cases of grade Ⅲ, 8 cases of grade Ⅳ, and 3 cases of grade Ⅴ. The preoperative visual analogue scale (VAS) score was 5.9±1.0, and the modified Mayo wrist score was 53.2±9.1. There were 2 cases of scaphoid nonunion advanced collapse, both of which were stage Ⅰ. All patients were treated with arthroscopic bone graft and Kirschner wire combined with screw fixation, and the fracture healing was observed by X-ray film monthly after operation, and the effectiveness was evaluated by VAS score and modified Mayo wrist score before and after operation.@*RESULTS@#All patients were followed up 6-14 months, with an average of 8.4 months. All fractures healed in 4-8 months, with an average of 6.3 months. The postoperative pain symptoms and wrist function of the patients significantly improved when compared with those before operation, and the VAS score at last follow-up was 2.4±1.3, and the modified Mayo wrist score was 87.1±6.7, which were significantly different from those before operation ( t=12.851, P<0.001; t=-14.410, P<0.001). According to the modified Mayo wrist evaluation, 9 cases were excellent, 3 cases were good, and 2 cases were fair.@*CONCLUSION@#Arthroscopic bone graft and Kirschner wire combined with screw fixation is an effective surgical method for the treatment of scaphoid fracture nonunion.

Feasibility study of predicting axillary lymph node metastasis of breast cancer using radiomics analysis based on dynamic contrast-enhanced MRI / 中华放射学杂志

Objective:To explore the feasibility of predicting axillary lymph node metastasis of breast cancer using radiomics analysis based on dynamic contrast-enhanced (DCE) MRI.Methods:The retrospective study enrolled 163 patients (163 lesions) with breast cancer diagnosed by core needle biopsy from January 2013 to December 2013 in Peking University First Hospital. The status of axillary lymph nodes in all patients was pathologically confirmed, and they had complete preoperative breast MRI images. Among the 163 patients, 94 patients were confirmed with axillary lymph node metastasis, and 69 patients without axillary lymph node metastasis. They were randomly divided into the training dataset ( n=115) and testing dataset ( n=48) in a 7∶3 ratio. The radiomics analysis was performed in the training dataset, including image preprocessing and labeling, radiomics feature extraction, radiomics model establishment and model predictive performance inspection. Model performance was tested in the testing dataset. Receiver operating characteristic curve and area under curve (AUC) was used to analyze the model prediction performance. Results:Of the 1 075 features extracted from the training dataset, principal component analyses (PCA) features 8, 41 and 67 were selected by random forest classifier. The radiomics model including 3 PCA features reached an AUC of 0.956 (95%CI 0.907-0.988), with sensitivity of 91.2%, specificity of 100% and accuracy of 94.8%. In the testing dataset, the radiomics model including 3 PCA features reached an AUC of 0.767 (95%CI 0.652-0.890), with sensitivity of 80.8%, specificity of 72.7% and accuracy of 77.1%.Conclusion:It is feasible to predict axillary lymph node metastasis using radiomics features based on DCE-MRI of breast cancer.

A family study of autosomal recessive primary familial brain calcification caused by JAM2 gene mutation and literature review / 中华神经科杂志

Objective:To improve the clinician′s recognition of the clinical and molecular characteristics of primary familial brain calcification (PFBC).Methods:The detailed clinical information, imaging and molecular characteristics were analyzed in proband and family members of a genetically confirmed autosomal recessive PFBC family. The clinical and imaging features of junctional adhesion molecule 2 (JAM2) gene related PFBC were analyzed in combination with the literature review.Results:The proband was a 32-year-old man, with slurred speech and paroxysmal limb twitch as the first symptoms, accompanied by cognitive dysfunction, and rigidity in the limbs, with epilepsy in the past. Brain CT showed extensive, symmetrical, and bilateral calcification involving the cerebellum, basal ganglia, thalamus, subcortex and cortex. Other family members showed no related clinical symptoms. Brain CT of the parents of the proband showed no calcification. Gene testing of the proband revealed a homozygous c.685C>T(p.R229*) mutation in JAM2 gene, which has been reported as a pathogenic variation abroad, whereas has not been reported in China. The proband′s parents and children were found with heterozygous c.685C>T (p.R229*) mutation.Conclusions:Autosomal recessive inherited PFBC is a rare disease, and JAM2 mutation is a newly discovered pathogenic gene of PFBC in 2020. Patients with intracranial calcification should be alert of JAM2 gene mutation.

Observation of the effect of autologous retinal pigment epithelium transplantation in the treatment of severe obsolete submacular hemorrhage / 中华眼底病杂志

Objective:To evaluate the functional and anatomical outcomes of autologous single retinal pigment epithelium (RPE) transplantation for severe obsolete submacular hemorrhage (SMH) in late age-related macular degeneration (AMD).Methods:A retrospective clinical study. From January 2012 to December 2015, 11 patients with AMD (11 eyes) with obsolete SMH who were diagnosed and treated by pars plana vitrectomy (PPV) combined with autologous RPE transplantation at the Department of Ophthalmology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were included. Among them, there were 9 eyes in 9 males and 2 eyes in 2 females. All the eyes underwent the examinations of best corrected visual acuity (BCVA) and optical coherence tomography; 4 eyes underwent macular fixation function (MAIA) at the same time. The BCVA examination was carried out using the international standard visual acuity chart, which was converted into logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. All eyes were treated with PPV combined with autologous single-layer RPE transplantation or autologous RPE-choroidal full-thickness transplantation, and were divided into S group and C group, with 5 and 6 eyes respectively. The differences of age ( t=-0.363), gender composition ratio ( χ2=0.549), course and thickness of SMH ( t=0.118, 0.231), average times of anti-vascular endothelial growth factor drug treatments ( t=0.129), times of PPV ( t=-0.452) between the two groups were not statistically significant ( P>0.05). The follow-up period was 6-40 months after the operation, and the BCVA, MAIA, graft status and complications of the eyes after the operation were observed. The comparison of continuous variables between groups was performed by independent-sample t test; the comparison of categorical variables was performed by χ2 test. Results:At the last follow-up, the average logMAR BCVA of the eyes in group S and C were 1.62±0.34 and 1.03±0.20, respectively; group C was better than group S, however, the difference was not statistically significant ( t=1.532, P=0.160). There were 4 eyes (80%, 4/5) and 6 eyes (100%, 6/6) in S group and C group with BCVA better than preoperative, the difference was no statistical significance ( χ2=0.677, P=0.895). There were 2 (40%, 2/5) and 3 (50%, 3/6) eyes with logMAR BCVA better than 1.0 in S group and C group, and the difference was not statistically significant ( χ2=0.572, P=0.423). After the operation, 6 eyes of grafts were in good condition and 5 eyes were in poor condition; the BCVA of grafts in good condition was significantly higher than that of poor condition, the difference was statistically significant ( t=4.894, P=0.001). Among the 4 eyes that underwent MAIA examination, 2 eyes were unstable and diffusely fixed on the graft; the fixation point was located at the normal retina adjacent to the graft area in 2 eyes. Secondary subretinal hemorrhage occurred in 3 eyes after the operation; the intraocular pressure was high in 1 eye after the operation. During the follow-up period, no intraocular infection, secondary retinal detachment, recurrent choroidal neovascularization or low intraocular pressure occurred in all eyes. Conclusions:Both autologous single-layer RPE transplantation and autologous RPE-choroidal full-thickness transplantation can help stabilize or even improve the visual function of eyes with severe SMH secondary to advanced AMD. The visual acuity after surgery is closely related to the state of the graft.

A feasibility study of classification between breast carcinoma in situ and invasive carcinoma using intratumoral and peritumoral radiomics based on dynamic contrast-enhanced MRI / 中华放射学杂志

Objective:To explore the feasibility of classification between carcinoma in situ and invasive carcinoma of breast using intratumoral and peritumoral radiomics based on breast dynamic contrast-enhanced (DCE) MRI.Methods:The retrospective study included consecutive invasive breast carcinoma pathological diagnosed by core needle biopsy or surgery from January 2013 to December 2013 and carcinoma in situ of breast diagnosed by surgery from January 2013 to December 2015 in Peking University First Hospital. All patients had pretreatment breast MRI images. A total of 251 cases (251 lesions) were included, with 208 invasive breast carcinoma and 43 carcinoma in situ of breast. They were all females and median age was 53 (23-82) years old. Patients were randomly divided into the training ( n=176) and testing dataset ( n=75) in a 7∶3 ratio. In the training dataset, combined with DCE mask and early enhancement images, intratumoral and peritumoral area were semi-automatic segmentation, and radiomics features were extracted and dimension reduction, finally a prediction model was established. Model performance was tested in the testing dataset. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to analyze the model prediction performance. Results:The prediction models established by intratumoral, peritumoral and intratumoral combined with peritumoral radiomics had good performance. The AUC of intratumoral, peritumoral and intratumoral combined with peritumoral radiomics prediction models in differentiating breast carcinoma in situ and invasive carcinoma were 0.865, 0.896 and 0.922 in the testing dataset, there was no significant difference in pairwise comparisons ( P>0.05). The sensitivity of intratumoral, peritumoral and intratumoral combined with peritumoral radiomics prediction models were 77.4%, 87.1%, 83.9%, the specificity were 92.3%, 84.6%, 100%, and the accuracy were 80.0%, 85.3%, 86.7%. Conclusion:It is potential feasible for classification between carcinoma in situ and invasive carcinoma of breast using intratumoral and peritumoral radiomics based on breast DCE MRI.

Imaging features of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusions: comparison with chromophobe renal cell carcinoma / 中华放射学杂志

Objective:To compare the imaging features of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 RCC) with chromophobe RCC.Methods:From November 2016 to January 2020, 28 patients with Xp11.2 RCC and 28 patients with chromophobe RCC confirmed by pathology were retrospectively analyzed in Peking University First Hospital. All 23 patients underwent preoperative CT examination, and 5 patients underwent routine MRI in each group. The clinical and imaging features were observed and recorded. The CT features including side, location, size, boundary, shape, uniform density, composition (solid, cystic-solid, cystic), hemorrhage, calcification, lymph node metastasis of the lesions and distant metastasis were observed, and the CT value of the solid part of the tumor at each stage was measured. On MRI images, the signal of the lesion in each sequence and enhancement mode were observed. The differences in clinical and imaging characteristics between the 2 groups were compared using independent samples t test or χ 2 test. Results:The Xp11.2 RCC more frequently affected young [(27±10) years] patients, while chromophobe RCC more frequently involved middle-aged [(37±7) years] patients asymptomatically, and the difference was statistically significant ( t=-4.99, P<0.001). The lesion size of Xp11.2 RCC [(5.4±2.2) cm] were significantly smaller than that of chromophobe RCC [(6.9±1.8) cm] ( t=-2.93, P=0.005). There were significant differences in the density and composition of lesions between Xp11.2 RCC and chromophobe RCC (χ 2=4.60, 18.67, P=0.032,<0.001). There were no significant differences in the side, location, boundary, shape, hemorrhage, calcification, fat, lymph node metastasis and distant metastasis between the 2 kind of lesions (all P>0.05). The CT values of solid components in Xp11.2 RCC in cortico-medullary phase and delayed phase were higher than those in chromophobe RCC, and the difference were statistically significant ( t=11.80, 20.15, both P<0.001). Five cases of Xp11.2 RCC showed iso- or slightly hyperintense signal on T 1WI and slightly hypointense signal on T 2WI. Two cases showed delayed enhancement after enhancement, and 3 cases showed a slight decrease in delayed phase enhancement. Conclusion:Compared with chromophobe RCC, Xp11.2 RCC has certain characteristics in imaging manifestations (lesion size, density uniformity, composition, CT value of post-enhanced cortico-medullary phase and delayed phase). Imaging manifestations combining the clinical manifestations (age of onset) are helpful for preoperative diagnosis of Xp11.2 RCC.

Clinical and genetic features of 12 families with Pompe disease / 中华神经医学杂志

Objective:To investigate the clinical and genetic features of Pompe disease, and analyze the effect of enzyme replacement therapy on it.Methods:A retrospective study was performed. The clinical data and genetic results of 14 patients with Pompe disease from 12 families, admitted to our hospital from January 2017 to June 2021, were collected. Some patients were followed up after therapies.Results:Twelve of the 14 patients were late onset, with onset age ranged from 1.5 to 37.0 years (mean 15.2 years), and the other 2 patients were infantile onset. The predominant manifestations included proximal lower limb weakness, accompanied by easy fatigue and myalgia; 8 patients presented with dyspnea, of which one had dyspnea as initial presentation. Serum creatine kinase ranged from 172 to 1397 IU/L (mean 878 IU/L). Electromyography revealed myogenic pattern in 6 patients and myotonic discharge in 4 patients. Forced vital capacity decreased in 10 patients, and scoliosis was detected in 5 patients; 13 patients had decreased acid-alpha-glucosidase (GAA) activity; muscle pathology indicated vacuolar myopathy in 8 patients. Genetic test revealed 17 variants in GAA gene, among which c.2331G>C, c.1622C>T, c.1585T>C, and c.1837T>C were 4 novel likely pathogenic variants. The c.2238G>C and c.2662G>T were found in 5 and 3 families, respectively. Muscle strength and lung function got improvement in 1 patient who received enzyme replacement therapy and had regular follow-up, while muscle strength and lung function were worsened in those who did not receive enzyme replacement therapy. Conclusions:Pompe disease is characterized by skeletal muscle weakness and pulmonary dysfunction, and may be associated with spinal deformity; creatine kinase is mildly to moderately elevated, and myotonic discharge can be detected. GAA c.2238G>C and c.2662G>T are hotspot mutations in China; the 4 novel variants enrich the GAA mutational spectrum. Enzyme replacement therapy may improve motor and pulmonary function.

Clinical characteristics and electron transfer flavoprotein dehydrogenase genetic mutations in 26 patients with riboflavin reactive lipid deposition myopathy / 中华神经医学杂志

Objective:To investigate the clinical characteristics and electron transfer flavoprotein dehydrogenase ( ETFDH) genetic mutations in patients with riboflavin responsive lipid storage myopathy (RR-LSM). Methods:A retrospective analysis was performed. The clinical data and muscular pathology of 26 patients with RR-LSM, admitted to our hospital from January 2009 to June 2021, were collected. Peripheral venous blood DNA was extracted, and the mutations of ETFDH gene were detected and analyzed by whole exome sequencing. Results:These 26 patients had onset of proximal limb myasthenia, 17 patients had difficulty in raising their head, 12 patients had mastication weakness, 6 had dysphagia, 5 had nausea and vomiting, and one was complicated with rhabdomyolysis and one was with reversible splenic lesion syndrome. Muscle biopsy indicated pathological deposition of lipid droplet, which type I fibers were involved mainly; degenerative necrotic muscle fibers were seen in a few cases. ETFDH gene mutations were detected in 26 patients; 23 patients had compound heterozygous mutation, two had single heterozygous mutation and one had homozygous mutation; 25 different mutation sites were found, mainly missense mutations; the C.770A>G frequency was the highest, accounting for 20% alleles (10/50); two novel mutation sites were found: c.1115A>G and c.1781T>C. Conclusion:RR-LSM is mainly characterized by proximal limb muscle weakness and fatigue intolerance, often accompanied by neck extensor and masticatory weakness; c. 770A>G is the hot site of ETFDH genetic mutations in RR-LSM patients.

TMEM16A inhibits angiotensin II-induced basilar artery smooth muscle cell migration in a WNK1-dependent manner

Vascular smooth muscle cell (VSMC) migration plays a critical role in the pathogenesis of many cardiovascular diseases. We recently showed that TMEM16A is involved in hypertension-induced cerebrovascular remodeling. However, it is unclear whether this effect is related to the regulation of VSMC migration. Here, we investigated whether and how TMEM16A contributes to migration in basilar artery smooth muscle cells (BASMCs). We observed that AngII increased the migration of cultured BASMCs, which was markedly inhibited by overexpression of TMEM16A. TMEM16A overexpression inhibited AngII-induced RhoA/ROCK2 activation, and myosin light chain phosphatase (MLCP) and myosin light chain (MLC20) phosphorylation. But AngII-induced myosin light chain kinase (MLCK) activation was not affected by TMEM16A. Furthermore, a suppressed activation of integrin

A novel mutation in the ABCD1 gene causes adrenomyeloneuropathy by impairing autophagy level / 中华神经科杂志

Objective:To report a Chinese family with a novel ABCD1 gene mutation at c.332T>G (p.V111G) site and discuss its clinical characteristics and molecular mechanism.Methods:The clinical data, laboratory examination, and imaging examination results were analyzed to make the clinical diagnosis of a middle-aged onset patient from the First Affiliated Hospital of Zhengzhou University in May 2017. High-throughput sequencing was used to discover a novel ABCD1 gene mutation. Sanger sequencing was used to find out whether other family members contain the same ABCD1 gene mutation. The pathogenicity of this mutation was explored by protein structure prediction and pathogenicity analysis. Adrenoleukodystrophy protein-green fluorescent protein (ALDP-GFP) and ALDP-GFP (V111G) plasmids were constructed and human embryonic kidney 293 cells were transfected, then immunofluorescence and Western blotting were used to explore the molecular mechanism of this mutation (completed in Henan Provincial People′s Hospital).Results:The proband (a 39-year-old male) was diagnosed as adrenomyeloneuropathy, a subset of X-linked adrenoleukodystrophy, with a novel heterozygous missense mutation in the ABCD1 gene at c.332T>G (p.V111G) site, and his mother and two daughters were all carriers. Protein structure prediction and pathogenicity results suggested that this mutation is pathogenic. Overexpression of ALDP-GFP (V111G) in the human embryonic kidney 293 cells resulted in a significant decrease in the expression levels of ALDP and the abnormal localization from the peroxisomal membrane to the cytoplasm, accompanied by significant down-regulation of LC3-Ⅱ/LC3-Ⅰ and beclin-1.Conclusion:c.332T>G (p.V111G) is a novel pathogenic mutation in the ABCD1 gene, which causes adrenomyeloneuropathy by impairing autophagy.

Clinical, myopathological and genetic features of two Chinese families with paramyotonia congenita / 中华内科杂志

Objective:To investigate the clinical, myopathological and genetic mutation characteristics in two Chinese families with paramyotonia congenita (PMC).Methods:Clinical manifestations, electrophysiology, muscle pathology and gene sequencing of two Chinese families with PMC were analyzed retrospectively.Results:Family 1 involved 12 patients in 4 consecutive generations and family 2 involved only 1 patient in 3 generations. The onset of symptoms in all patients started at early childhood. Both probands presented with myotonia triggered by cold and paroxysmal weakness. However, the other 11 patients in family 1 only manifested cold-induced myotonia. Serum creatine kinase (CK) was slightly elevated between attacks of weakness in the 2 probands, and was even greater than 10 000 U/L during the episodes of weakness in the second proband, whose lower limb MRI revealed edema in bilateral medial gastrocnemius. Electromyography showed diffuse myotonia discharge and myogenic impairment in both probands, and myotonia discharge in the first proband′s mother. Muscle pathology of both probands showed mild myopathic changes, and tube aggregation was occasionally observed in the second one. Genetic testing revealed a maternally inherited heterozygous R1448H mutation of SCN4A gene in the first proband and part of his family. A novel heterozygous R1448G mutation of SCN4A gene was reported in the second proband.Conclusions:Cold-triggered myotonia with or without paroxysmal weakness are the common characteristics of PMC. Myotonic potential and myogenic impairment can be tested in electromyography. The p.R1448G mutation is a new missense mutation.

Identification of SPAST gene variant in a pedigree affected with hereditary spastic paraplegia type 4 / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a pedigree affected with hereditary spastic paraplegia type 4 (HSP4).@*METHODS@#Peripheral venous blood samples were taken from members of the four-generation pedigree and 50 healthy controls for the extraction of genomic DNA. Genes associated with peripheral neuropathy and hereditary spastic paraplegia were captured and subjected to targeted capture and next-generation sequencing. The results were confirmed by Sanger sequencing.@*RESULTS@#DNA sequencing suggested that the proband has carried a heterozygous c.1196C>G variant in exon 9 of the SPAST gene, which can cause substitution of serine by threonine at position 399 (p.Ser399Trp) and lead to change in the protein function. The same variant was also detected in other patients from the pedigree but not among unaffected individuals or the 50 healthy controls. Based on the ACMG 2015 guidelines, the variant was predicted to be possibly pathogenic.@*CONCLUSION@#The c.1196C>G variant of the SPAST gene probably underlay the HSP4 in this pedigree.

Analysis of a pedigree with autosomal dominant intermediate Charcot-Marie-Tooth disease type E and nephropathy / 中华医学遗传学杂志

OBJECTIVE@#To explore phenotypic and mutational characteristics of a pedigree affected with autosomal dominant Charcot-Marie-Tooth disease (CMT) and nephropathy.@*METHODS@#Clinical data of the proband and his family members was collected. Electrophysiology, renal biopsy and next-generation sequencing were carried out for the proband.@*RESULTS@#The proband presented with distal lower limb weakness and proteinuria in childhood. His mother and brother had similar symptoms. Electrophysiological test of the proband revealed demyelination and axonal changes in both motor and sensory nerves. Renal biopsy suggested focal segmental glomerulosclerosis. Genetic testing revealed a heterozygous c.341G>A (p.G114D) mutation in exon 2 of the INF2 gene.@*CONCLUSION@#The phenotypic feature of the pedigree is autosomal dominant intermediate CMT and focal segmental glomerulosclerosis, which may be attributed to the c.341G>A mutation of the INF2 gene.