Large Chinese Cohort Research Articles

Association of Gestational Hypertension with Anemia under 5 Years Old: Two Large Longitudinal Chinese Birth Cohorts.

Gestational hypertension may interfere with the placental iron metabolism, thus probably increasing the risk of childhood anemia. We aim to examine the association between gestational hypertension and childhood anemia at different ages in two large Chinese birth cohorts. Cohort 1 was conducted in 5 counties in northern China and was comprised of 17,264 mother–children pairs (97.3%) during 2006–2009, whereas cohort 2 was conducted in 21 counties in southern China and was comprised of 185,093 mother–children pairs (93.8%) during 1993–1996. All pregnant women were registered in a monitoring system and followed up until the termination of pregnancies. The childhood anemia was diagnosed at 6 month and 12 month in cohort 1 and at 55 month in cohort 2. The overall incidence of childhood anemia was 6.78% and 5.28% at 6 month and 12 month, respectively, in cohort 1 and 13.18% at 55 month in cohort 2. Gestational hypertension was associated with increased risk of anemia at 6 month (adjusted Odds Ratio (OR): 1.31; 95% confidence interval (CI): 1.05, 1.63) and at 12 month (adjusted OR: 1.50; 95% CI: 1.18, 1.90) in cohort 1 and at 55 month (adjusted OR: 1.06; 95% CI: 1.01, 1.12) in cohort 2. The hemoglobin values of children at different ages were lower among gestational hypertension group in the linear models, which was consistent with the results of binary regression analysis. Our study found gestational hypertension may associate with an increased risk of childhood anemia. It suggests a possible need for exploring changes in prenatal care that might prevent childhood anemia.

Correlation of Body Mass Index with Epidermal Biophysical Properties Varies with Gender in Chinese

Background: Epidermal function is associated with diabetes and renal disease. Whether obesity can reflect the changes in epidermal function is not clear yet. Objective: We assessed here the correlation of epidermal functions with body mass index (BMI) in a large Chinese cohort. Methods and Subjects: A total of 1,405 Chinese aged 21–98 years old were enrolled in this study. Epidermal functions, including transepidermal water loss (TEWL), stratum corneum hydration, and skin surface pH, were measured on the flexor forearm and the shin. Subjects’ height and body weight were also measured. Results: Age positively correlated with both TEWL and skin surface pH, while it negatively correlated with stratum corneum hydration on both the forearm and the shin of females. Similarly, age positively correlated with skin surface pH, while negatively correlating with stratum corneum hydration on both the forearm and the shin of males. In females, BMI positively correlated with skin surface pH, while it negatively correlated with stratum corneum hydration on both the forearm and the shin. However, BMI correlated neither with skin surface pH on both the forearm and the shin nor with stratum corneum hydration on the shin of males. Conclusion: These results demonstrate that correlations of BMI with age and epidermal functions vary with gender.

Familial hypercholesterolemia in China requires greater efforts

Familial hypercholesterolemia in China requires greater efforts

An analysis on the determinants of head to pelvic balance in a Chinese adult population.

Balanced global spinopelvic balance is important in the maintenance of the physiological alignment of all body segments above the pelvis with minimum energy expenditure. The key determinants affecting the 3D index-odontoid-hip axis (OD-HA) angle, and in particular its alterations, have not been clearly defined. The aim of this study is to identify the determinants of the 3D OD-HA angle in maintaining global spinopelvic balance in a large Chinese adult cohort of different gender and age groups. A total of 516 asymptomatic adults were enrolled in this study. Biplanar radiographies were performed to reconstruct the subject's inter-acetabular axis and C2 odontoid process. The 3D angle formed by the vertical and the line between odontoid and mid-interacetabular axis (OD-HA angle) was computed and projected in the subject's sagittal and coronal planes. Thoracic kyphosis (TK), lumbar lordosis (LL), T1 pelvic angle (TPA) and sagittal vertical axis (SVA) were measured. The mean values of sagittal and coronal OD-HA were -0.2°±2.5° and 0.2°±1.1°, respectively. Both sagittal and coronal OD-HA had significant correlation with age (r=0.265 and r=-0.143, P<0.01, respectively), sagittal OD-HA showed increment from 20s to 80s (-1.3° to 0.8° for female, -0.3° to 1.5° for male) and a significant difference between male and female from 20 to 69 years old. Further analysis showed that sex, weight, TK, PT, SVA, TPA and ODI were determinants of OD-HA. 3D OD-HA angle showed physiological stability with little variability from young to elderly adults, with SD of 2.45° and 1.06° in sagittal and coronal planes, respectively. OD-HA angle confirms the hypothesis that the head tends to remain above the pelvis in a small cone of stability. This study provides an analysis of the determinants of OD-HA and the reference range of the head-pelvis balance in each decade and gender based on a large-scale asymptomatic population.

Loss-of-function of KMT5B leads to neurodevelopmental disorder and impairs neuronal development and neurogenesis

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders that cause severe social, communication, and behavioral problems. Recent studies show that the variants of a histone methyltransferase gene KMT5B cause neurodevelopmental disorders (NDDs), including ASD, and the knockout of Kmt5b in mice is embryonic lethal. However, the detailed genotype-phenotype correlations and functional effects of KMT5B in neurodevelopment are unclear. By targeted sequencing of a large Chinese ASD cohort, analyzing published genome-wide sequencing data, and mining literature, we curated 39 KMT5B variants identified from NDD individuals. A genotype-phenotype correlation analysis for 10 individuals with KMT5B pathogenic variants reveals common symptoms, including ASD, intellectual disability, languages problem, and macrocephaly. In vitro knockdown of the expression of Kmt5b in cultured mouse primary cortical neurons leads to a decrease in neuronal dendritic complexity and an increase in dendritic spine density, which can be rescued by expression of human KMT5B but not that of pathogenic de novo missense mutants. In vivo knockdown of the Kmt5b expression in the mouse embryonic cerebral cortex by in utero electroporation results in decreased proliferation and accelerated migration of neural progenitor cells. Our findings reveal essential roles of histone methyltransferase KMT5B in neuronal development, prenatal neurogenesis, and neuronal migration.

Etiologic Classification of 541 Infantile Spasms Cases: A Cohort Study.

ObjectiveTo explore the etiology of infantile spasms (IS) in a large Chinese cohort based on the United States National Infantile Spasms Consortium (NISC) classification.MethodsIn the present study, we recruited IS patients diagnosed at a single center (Xiangya Hospital, Central South University) between Jan 2010 and Aug 2019. Thereafter, we collected their clinical and genetic information retrospectively. Their underlying etiologies were classified according to the NISC classification and then compared in different scenarios to understand their distribution.ResultsA total of 541 patients with IS from 18 provinces were included in this study. The underlying etiology was identified in 53.2% of the cases: structural-acquired, 25.3%; genetic, 12.9%; genetic-structural, 7.2%; structural-congenital, 5.0%; metabolic, 2.4%; infections, 0.4% and immune, 0%. Whole-exome sequencing (WES) provided the highest diagnostic yield (26.9%). In structural-acquired IS, the proportion of hypoglycemic brain injuries was significant, second only to hypoxic-ischemic encephalopathy. There was no patient discovered to have Down syndrome. STXBP1, CDKL5, TSC2, KCNQ2, IRF2BPL, and TSC1 were the most frequently implicated genes. Genetic causes were found to be the most common cause of IS in the early onset group, while structural-acquired etiologies were common in males and preterm babies. Patients with pre-spasm seizures were associated with a higher proportion of identified causes than those without. Non-acquired structural etiologies were more common in patients without hypsarrhythmia than in those with hypsarrhythmia.SignificanceThe most prevalent cause of IS was structural acquired followed by genetic causes. When brain MRI fails to detect the etiology, we propose WES as the next step. Structural-acquired IS and cases with genetic disorders are characteristic of the Chinese cohort, however, the etiology differs with the patient's age of onset, gestation age at birth, sex, and the presence/absence of both pre-spasm seizures, and hypsarrhythmia.

Evaluation of common and rare variants of Alzheimer's disease-causal genes in Parkinson's disease

IntroductionParkinson's disease (PD) and Alzheimer's disease (AD) are the most common neurodegenerative diseases in the elderly. Recently, some variants of AD-causal genes (APP, PSEN1, PSEN2) have been reported in PD. In this study, we investigated the association between coding variants of AD‐causal genes and PD in a large Chinese population cohort. MethodsWe performed whole-exome sequencing (WES) on 1,917 patients with early-onset or familial PD and 1,652 controls, and whole-genome sequencing (WGS) on 1,962 sporadic late-onset PD and 1,279 controls. Genetic and phenotypic data were analyzed with regression analyses and the optimized sequence kernel association test. Further validation study was performed by Fisher's exact test. ResultsWe found that rs75733498 in the PSEN2 gene was significantly associated with early-onset or familial PD; however, no significant relationship was discovered between rs75733498 and sporadic late-onset PD. The result of the validation study still revealed a significant association between rs75733498 and PD. We observed a suggestive association with APP gene in early-onset or familial PD when considering damaging missense variants alone (p = 0.018) or combined with loss‐of‐function variants (p = 0.029). Further phenotypic analysis did not demonstrate any significant associations. ConclusionOur results support a possible genetic contribution of AD-causal genes to PD. These findings warrant further genetic and functional confirmation, and more powerful association studies will better decipher the mechanisms of PD.

Association of Infants Small for Gestational Age with Anemia under Five Years Old in Two Large Longitudinal Chinese Birth Cohorts.

Babies who are born small for their gestational age (SGA) have low iron reserves, thus probably increasing the risk of offspring anemia. We studied two longitudinal birth cohorts to evaluate the association of SGA with the risk of anemia during early childhood. Cohort 1 was recruited from five counties in northern China involving 17,180 singleton infants born during 2006–2009 and cohort 2 from 21 counties or cities in southern China involving 180,619 children born during 1993–1996. Anemia was diagnosed by hemoglobin at 6 and 12 months in cohort 1 and at 55 months in cohort 2. The overall incidences of SGA were 7.07% and 5.73% in cohort 1 and cohort 2, respectively. SGA was associated with increased anemia at 6 months (adjusted odds ratio (OR): 1.52; 95% confidence interval (CI): 1.24, 1.86) and 12 months (adjusted OR: 1.42; 95% CI: 1.13, 1.79) in cohort 1 and at 55 months (adjusted OR: 1.11; 95% CI: 1.05, 1.17) in cohort 2. The positive associations for anemia at 6, 12, and 55 months persisted in both logistics and multiple linear models. Our results support a gradually decreased association between SGA and the increased risk of childhood anemia with a longer follow-up time in infants and children.

Association of prenatal renal ultrasound abnormalities with pathogenic copy number variants in a large Chinese cohort.

To assess the clinical utility of prenatal chromosomal microarray analysis (CMA) in fetuses with abnormal renal sonographic findings, and to evaluate the association of pathogenic or likely pathogenic copy number variants (P/LP CNVs) with different types of renal abnormality. This was a retrospective study of fetuses at 14-36 weeks screened routinely for renal and other structural abnormalities at the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. We retrieved and analyzed data from fetuses with abnormal renal sonographic findings, examined between January 2013 and November 2019, which underwent CMA analysis using tissue obtained from chorionic villus sampling (CVS), amniocentesis or cordocentesis. We evaluated the CMA findings according to type of renal ultrasound anomaly and according to whether renal anomalies were isolated or non-isolated. Ten types of renal anomaly were reported on prenatal ultrasound screening, at a mean ± SD gestational age of 24.9 ± 4.8 weeks. The anomalies were diagnosed relatively late in this series, as 64% of cases with an isolated renal anomaly underwent cordocentesis rather than CVS. Fetal pyelectasis was the most common renal ultrasound finding, affecting around one-third (34.32%, 301/877) of fetuses with a renal anomaly, but only 3.65% (n = 11) of these harbored a P/LP CNV (comprising: isolated cases, 2.37% (4/169); non-isolated cases, 5.30% (7/132)). Hyperechogenic kidney was found in 5.47% (n = 48) of fetuses with a renal anomaly, of which 39.58% (n = 19) had a P/LP CNV finding (comprising: isolated cases, 44.44% (16/36); non-isolated cases, 25.00% (3/12)), the highest diagnostic yield among the different types of renal anomaly. Renal agenesis, which accounted for 9.92% (n = 87) of all abnormal renal cases, had a CMA diagnostic yield of 12.64% (n = 11) (comprising: isolated cases, 11.54% (9/78); non-isolated cases, 22.22% (2/9); unilateral cases, 11.39% (9/79); bilateral cases, 25.00% (2/8)), while multicystic dysplastic kidney (n = 110), renal cyst (n = 34), renal dysplasia (n = 27), crossed fused renal ectopia (n = 31), hydronephrosis (n = 98), renal duplication (n = 42) and ectopic kidney (n = 99) had overall diagnostic rates of 11.82%, 11.76%, 7.41%, 6.45%, 6.12%, 4.76% and 3.03%, respectively. Compared with the combined group of CMA-negative fetuses with any other type of renal anomaly, the rate of infant being alive and well at birth was significantly higher in CMA-negative fetuses with isolated fetal pyelectasis or ectopic kidney, whereas the rate was significantly lower in fetuses with isolated renal agenesis, multicystic dysplastic kidney or severe hydronephrosis. The most common pathogenic CNV was 17q12 deletion, which accounted for 30.14% (22/73) of all positive CMA findings, with a rate of 2.51% (22/877) among fetuses with an abnormal renal finding. Fetuses with 17q12 deletion exhibited a wide range of renal phenotypes. Other P/LP CNVs in the recurrent region that were associated with prenatal renal ultrasound abnormalities included 22q11.2, Xp21.1, Xp22.3, 2q13, 16p11.2 and 1q21, which, collectively, accounted for 2.17% (19/877) of the fetuses with prenatal renal anomalies. In this retrospective review of CMA findings in a large cohort of fetuses with different types of renal ultrasound abnormality, the P/LP CNV detection rate varied significantly (3.03-39.58%) among the different types of kidney anomaly. Our data may help in the decision regarding whether to perform prenatal genetic testing in fetuses with renal ultrasound findings. Specifically, prenatal CMA testing should be performed in cases of hyperechogenic kidney, regardless of whether or not the anomaly is isolated, while it should be performed postnatally rather than prenatally in cases of fetal pyelectasis. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Reclassification of patients with tremor syndrome and comparisons of essential tremor and essential tremor-plus patients.

The new essential tremor (ET)-plus nomenclature was proposed by the 2018 Tremor Consensus Criteria. However, few studies have adopted this usage and the clinical differences between ET and ET-plus remains unclear. To address this issue, we reclassified and compared the characteristics of ET and ET-plus patients in a large Chinese tremor cohort. In this cross-sectional observational study, 766 patients originally diagnosed with ET underwent neurological examination. Scale ratings were used to evaluate motor and non-motor symptoms, and quality of life (QoL). We then reclassified the ET cohort and compared demographic and clinical characteristics between ET and ET-plus patients. A logistic regression analysis was used to explore whether the presence of neurological soft signs in ET-plus was associated with tremor severity or QoL. Among 665 clinically confirmed ET syndrome patients, 274 were ET and 391 were ET-plus. The most prevalent neurological soft sign was resting tremor. ET-plus patients were older, had older age at onset and longer disease duration. ET-plus patients recorded higher scores in tremor severity evaluations and lower in cognitive evaluations, whereas a higher proportion of patients presented with depression or anxiety symptoms. Resting tremor and questionable cerebellar signs were associated with tremor severity. Cognitive impairment was associated with worse QoL. ET-plus patients were older, had longer disease durations, worse tremor manifestations, and more distinct non-motor symptoms. Certain additional soft signs of ET-plus were associated with tremor severity or worse QoL. ET-plus patients may include advanced ET patients with additional neurological soft signs presenting along with disease progression.

Prevalence and genotype-phenotype correlations of GBA-related Parkinson disease in a large Chinese cohort.

Background and purposeVariants in the glucocerebrosidase (GBA) gene are recognized as a common and important genetic risk factor for Parkinson disease (PD). However, the impact of variant severity on the clinical phenotype of PD in the Chinese population remains unclear. Thus, the present study aimed to determine the frequency of GBA‐related PD (GBA‐PD) and the relationship of GBA variant severity with clinical characteristics in a large Chinese cohort.MethodsLong‐range polymerase chain reaction and next generation sequencing were performed for the entire GBA gene. GBA variant severity was classified into five classes: mild, severe, risk, complex, and unknown.ResultsAmong the total 737 PD patients, 47 GBA variants were detected in 79 (10.72%) patients, and the most common GBA variants were R163Q, L444P, and R120W. Complete demographic and clinical data were obtained for 673 patients, which revealed that 18.50% of early onset PD patients had GBA variants. Compared with patients without GBA variants, GBA‐PD patients experienced PD onset an average of 4 years earlier and had more severe motor and nonmotor symptoms. Patients carrying severe and complex variants had a higher burden of nonmotor symptoms, especially depression, and more mood/cognitive and gastrointestinal symptoms than patients carrying mild variants.Conclusions GBA‐PD is highly prevalent in the Chinese population. The severity of GBA variants underlies distinct phenotypic spectrums, with PD patients carrying severe and complex variants seeming to have similar phenotypes. PD patient stratification by GBA variant severity should become a prerequisite for selecting specific treatments.

Association of Chinese Visceral Adiposity Index and Its Dynamic Change With Risk of Carotid Plaque in a Large Cohort in China.

BackgroundWe aimed to evaluate the association between the Chinese visceral adiposity index (CVAI) and its dynamic change and risk of carotid plaque based on a large Chinese cohort.Methods and ResultsThis cohort included 23 522 participants aged 20 to 80 years without elevated carotid intima‐media thickness and carotid plaque at baseline and who received at least 2 health checkups. CVAI was calculated at baseline and at every checkup. The dynamic change in CVAI was calculated by subtracting CVAI at baseline from that at the last follow‐up. Cox proportional hazard regression model was used to estimate hazard ratios (HRs) and 95% CIs. The restricted cubic spline was applied to model the dose‐response association between CVAI and carotid plaque risk. During the 82 621 person‐years of follow‐up, 5987 cases of carotid plaque developed (7.25/100 person‐years). We observed a significant positive correlation between CVAI and carotid plaque risk (HR, 1.53; 95% CI, 1.48–1.59 [P<0.001]) in a nonlinear dose‐response pattern (P nonlinearity<0.001). The sensitivity analyses further confirmed the robustness of the results. The association was significant in all subgroup analyses stratified by sex, hypertension, and fatty liver disease except for the diabetes subgroup. The association between CVAI and carotid plaque risk was much higher in men than in women. No significant association was identified between change in CVAI and carotid plaque risk.ConclusionsCVAI was positively associated with carotid plaque risk in a nonlinear dose‐response pattern in this study. Individuals should keep their CVAI within a normal level to prevent the development of carotid plaque.

Nomogram Model for Dynamic and Individual Prediction of Cardiac Response and Survival for Light Chain Amyloidosis in 737 Patients With Cardiac Involvement.

ObjectiveLight chain amyloidosis (AL) with cardiac involvement is associated with poor prognosis. The existing prognostic assessment system does not consider treatment-related factors, and there is currently no effective system for predicting the response. The purpose of this study was to build an individualized, dynamic assessment model for cardiac response and overall survival (OS) for AL patients with cardiac involvement.MethodsThe records of 737 AL patients with cardiac involvement were collected through cooperation with 18 hospitals in the Chinese Registration Network for Light-chain Amyloidosis (CRENLA). We used univariate and multivariate analyses to evaluate the prognostic factors for OS and cardiac response. Then, two nomogram models were developed to predict OS and cardiac response in AL patients with cardiac involvement.ResultsA nomogram including four independent factors from the multivariate Cox proportional hazards analysis—Mayo staging, courses of treatment, hematologic response, and cardiac response—was constructed to calculate the possibility of achieving survival by adding all the points associated with four variables. The higher the score, the more likely death would occur. The other nomogram model included the courses of treatment, hematological response, and different treatment regimens, and was correlated with cardiac response. The higher the score, the more likely a cardiac response would occur.ConclusionIn conclusion, based on the large Chinese cohort of patients with AL and cardiac involvement, we identified nomogram models to predict cardiac response and OS. These models are more individualized and dynamic, and therefore, they have important clinical application value.

Characteristics of Autonomic Dysfunction in Parkinson’s Disease: A Large Chinese Multicenter Cohort Study

Autonomic dysfunction (AutD) is one of the non-motor symptoms (NMSs) in Parkinson’s disease (PD). To investigate the prevalence and clinical features of AutD in Chinese patients with PD, a large multicenter cohort of 2,556 individuals with PD were consecutively involved in the Parkinson’s Disease and Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) between January 1, 2017, and December 31, 2019. The assessment of AutD was performed using the Scale for Outcomes in Parkinson’s Disease for Autonomic Symptoms (SCOPA-AUT). The evaluation of motor symptoms and other NMSs were performed using well-established scales recommended by the Movement Disorder Society. We found that out of 2,556 patients with PD, 2,333 patients with PD (91.28%) had AutD. Compared with the group of patients with PD without AutD, the group of patients with PD with AutD had older age, older age of onset, longer disease duration, more severe motor symptoms, motor complications, and more frequent NMSs. As for partial correlation analysis, the total SCOPA-AUT score was significantly and positively associated with motor severity scales [Unified Parkinson’s Disease Rating Scale (UPDRS) total score] and some of the NMSs [Rapid Eye Movement Sleep Behavior Disorder Questionnaire (RBD), Epworth Sleepiness Scale, Hamilton Depression Scale], Fatigue Severity Scale, and Parkinson’s disease questionnaire. PD Sleep Scale was significantly and negatively correlated with AutD. With logistic regression analysis for potentially related factors, age, UPDRS total score, RBD, hyposmia, depression, and fatigue may be associated with PD with AutD. In conclusion, our multicenter cohort study reported the high prevalence of AutD in Chinese PD and revealed the associated factors of PD with AutD.

Place of death and phenomenon of going home to die in Chinese adults: A prospective cohort study

SummaryBackgroundChina is embracing an ageing population without sustainable end-of-life care services. However, changes in place of death and trends of going home to die (GHTD) from the hospital remains unknown.MethodsA total of 42,956 participants from the China Kadoorie Biobank, a large Chinese cohort, who died between 2009 and 2017 was included into analysis. GHTD was defined as death at home within 7 days after discharge from the hospital. A modified Poisson regression was used to investigate temporal trends of the place of death and GHTD, and estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for the association of GHTD with health insurance (HI) schemes.FindingsFrom 2009 to 2017, home remained the most common place of death (71·5%), followed by the hospital (21·6%). The proportion of GHTD for Urban and Rural Residents’ Basic Medical Insurance (URRBMI) beneficiaries was around six times higher than that for Urban Employee Basic Medical Insurance (UEBMI) beneficiaries (66·0% vs 11·6%). Besides, a substantial increase in the proportion of GHTD throughout the study period was observed regardless of HI schemes (4·4% annually for URRBMI, and 5·4% for UEBMI). Compared with UEBMI beneficiaries, URRBMI beneficiaries were more likely to experience GHTD, with an adjusted PR (95% CI) of 1·19 (95% CI: 1·12, 1·27) (P<0·001).InterpretationIn China, most of deaths occurred at home, with a large proportion of decedents GHTD from the hospital, especially for URRBMI beneficiaries. Substantial variation in the phenomenon of GHTD across HI schemes indicates inequalities in end-of-life care utilization.FundingThe National Natural Science Foundation of China, the Kadoorie Charitable Foundation, the National Key R&D Program of China, the Chinese Ministry of Science and Technology.

Clinical and Genetic Features of Biallelic Mutations in SORD in a Series of Chinese Patients With Charcot-Marie-Tooth and Distal Hereditary Motor Neuropathy.

Biallelic mutations in the sorbitol dehydrogenase (SORD) gene have recently been found to be one of the most frequent causes of autosomal recessive axonal Charcot-Marie-Tooth (CMT2) and distal hereditary motor neuropathy (dHMN). This study was performed to explore the frequency of SORD mutations and correlations of the phenotypic-genetic spectrum in a relatively large Chinese cohort. In this study, we screened a cohort of 485 unrelated Chinese patients with hereditary neuropathy by using Sanger sequencing, next generation sequencing, or whole exome sequencing after PMP22 duplication was initially excluded. SORD mutation was identified in five out of 78 undiagnosed patients. Two individuals carried the previously reported homozygous c.757 delG (p.A253Qfs*27) variant, and three individuals carried the heterozygous c.757delG (p.A253Qfs*27) variant together with a second novel likely pathogenic variant, including c.731 C>T (p.P244L), c.776 C>T (p.A259V), or c.851T>C (p.L284P). The frequency of SORD variants was calculated to be 6.4% (5/78) in unclarified CMT2 and dHMN patients. All patients presented with distal weakness and atrophy in the lower limb, two of whom had minor clinical sensory abnormalities and small fiber neuropathy. Our study provides further information on the genotype and phenotype of patients with SORD mutations.

The Genotype and Phenotype Features in a Large Chinese MFN2 Mutation Cohort.

Introduction: Charcot–Marie–Tooth disease type 2A (CMT2A) is a group of clinically and genetically heterogeneous disorders, which is mostly caused by mutations of the mitofusin2 (MFN2) gene. As the genotype–phenotype characteristics of CMT2A were still incompletely understood, we further explored the spectrum of CMT2A variants in China and demonstrated their phenotypic diversities.Methods: A total of 402 index patients/families with CMT throughout Mainland China were enrolled in this study. Among them, we analyzed 20 unrelated index cases with CMT2A by Sanger sequencing, next-generation sequencing, or whole-exome sequencing. Detailed clinical and genetic features of CMT2A patients were collected and analyzed. Of note, de novo mutations were not rare in MFN2 gene; we compared the clinical features of patients from the de novo group with those from the non-de novo group.Results: We identified 20 MFN2 variants, occupying 5.0% of CMT. Most patients presented with early onset and moderate phenotype with abnormal gait and foot drop as the main complaints at onset. Pyramidal signs accounts for 31.6% (6/19) in all patients, which is not uncommon. Four novel variants (p.Tyr752*, c.475-2A>G, p.Val99Met, and p.Arg275_Gln276insArg) were identified in the cohort. Besides, de novo variants occupied 35.0% (7/20) in our study with a much earlier age at onset compared with those in the non-de novo group (p = 0.021).Conclusion: Chinese CMT2A is a predominant typical pure CMT2A, with early onset and mild to moderate phenotype. Given the high frequency of de novo MFN2 mutations, genetic study should be considered for patients with early onset and severe idiopathic axonal neuropathy.

Association between Diabetes Complications and the Triglyceride-Glucose Index in Hospitalized Patients with Type 2 Diabetes.

Background Triglyceride-glucose (TyG) index is a convenient indicator of insulin resistance. It has been shown to be associated with macrovascular and microvascular complications in nonhospitalized diabetic patients. However, whether TyG index is a risk factor of diabetes vascular complications in hospitalized type 2 diabetic patients is unclear. We sought to explore the association between TyG index and the risk of macrovascular and microvascular complications in a large Chinese cohort of hospitalized patients. Method A total of 4,721 patients with type 2 diabetes (T2D) who were hospitalized in the Department of Endocrinology, Kunshan Hospital Affiliated to Jiangsu University were enrolled between January 2015 and November 2020. TyG index was calculated as ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Measures of macrovascular complications included brachial-ankle pulse wave velocity (ba-PWV) and ankle-brachial index (ABI), whilst urine microalbumin (MAU), chronic kidney disease (CKD), and diabetic retinopathy (DR) were evaluated for microvascular complications. Logistic regressions were used to examine the association between TyG index and diabetes complications. Results In univariate logistic regressions, higher TyG index was significantly (p < 0.002) associated with increased odds of MAU (OR = 1.39, 95% CI: [1.22~1.59]) and ABI (OR = 1.31, 95% CI: [1.10-1.57]) but not CKD, DR, or ba-PWV. After controlling for confounders such as age, sex, and body mass index (BMI), TyG index remained strongly (p < 0.002) associated with MAU and ABI. These associations were more pronounced (p < 0.001) in patients with poor glycemic control or in the elderly. Conclusion Hospitalized patients with an elevated TyG index were at a higher risk of lower limb vascular stenosis and nephric microvascular damage. Close monitoring of TyG index in patients with younger age or poor glycemic control could potentially reduce the burden of diabetes complications and prevent readmission.

Prevalence of Polypoidal Choroidal Vasculopathy Using Non-indocyanine green angiography–based Criteria

Polypoidal choroidal vasculopathy (PCV) is a form of neovascular AMD characterized by polypoidal lesions and branching vascular networks. Diagnosis has traditionally required the use of invasive indocyanine green angiography, though recently a validated non-invasive diagnostic system has been developed that identified PCV-specific features using optical coherence tomography (OCT) and color fundus photography. In this work we applied this new system to a large population-based cohort of ethnic Chinese and successfully identified PCV and related anatomical features. We estimated a population prevalence of 0.31% (95% CI, 0.06-0.91%) and additionally demonstrate that PCV-related retinal findings were relatively rare in the population.

Assessment of Acute Mountain Sickness Using 1993 and 2018 Versions of the Lake Louise Score in a Large Chinese Cohort.

Chen, Renzheng, Yong Wang, Chen Zhang, Xiaolin Luo, Jie Yang, Chuan Liu, and Lan Huang. Assessment of acute mountain sickness using 1993 and 2018 versions of the Lake Louise Score in a large Chinese cohort. High Alt Med Biol. 22:362-368, 2021. Background: This study uses Lake Louise Score (LLS) in its original (LLS1993) and new (LLS2018) versions to assess acute mountain sickness (AMS) and aims to provide more clinical information about the AMS scoring system. Methods: We enrolled 1,026 male Chinese soldiers who traveled from an altitude of 500 to 3,700 m by airplane in 2.5 hours. We observed each subject's symptoms after arrival at 3,700 m in 24 and 48 hours. Each item was dropped from LLS1993 to evaluate its sensitivity and effect on AMS diagnosis. The relationship between each symptom and AMS was assessed by correlation analysis. Exploratory and confirmatory factor analyses evaluated the factor structure of LLS, while the ordinal alpha coefficient was calculated to determine its internal consistency. Results: Four hundred fifty-nine subjects were not followed up on day 2. We defined two observed cohorts (cohort 1, n = 1,026 and cohort 2, n = 567). Headache was the most common symptom in 24 hours, while sleep disturbance was the fourth-most common symptom at 24 hours and the most common symptom at 48 hours. When we dropped gastrointestinal symptoms, the drop rate was lowest in each situation (1.0% in cohort 1, 1.3% in cohort 2 at 24 hours, and 5.7% in cohort 2 at 48 hours, respectively). The incidence of AMS decreased from 18.4% at 24 hours to 36.4% at 48 hours when lost sleep disturbance in cohort 2. Moreover, the statistical method of Mantel/Haenszel square test was used for correlation analysis and the results showed a correlation between sleep disturbance and AMS. Besides, both LLS1993 and LLS2018 had acceptable internal consistencies, and all items had good loading coefficients in LLS1993. Conclusions: We have demonstrated that there could be an association between sleep disturbance and AMS diagnosis. Both LLS1993 and LLS2018 applied to young Chinese men.