X-linked adrenoleukodystrophy(X-ALD) is an inherited progressive neurometabolic disorder caused by mutations in the ATP-binding cassette subfamily D member 1(ABCD1) gene. The encoded ALD protein dysfunction leads to the accumulation of very-long-chain fatty acids(VLCFA). X-ALD is classified according to its clinical characteristics into childhood cerebral ALD, adolescent cerebral ALD, adult cerebral ALD, adrenomyeloneuropathy(AMN), pure adrenocortical insufficiency, and an asymptomatic phenotype, all of which can present with a variety of neurologic manifestations. In this study, we retrospectively analyzed the clinical manifestations, laboratory findings, genetic test results, and follow-up data of four patients with X-ALD, and investigated the clinical features and pathogenicity of the identified gene mutations. All four patients initially presented with adrenocortical insufficiency(Addison′s disease) and received glucocorticoid replacement therapy. Subsequently, all developed neurologic signs and symptoms with rapid progression. The final diagnosis was confirmed based on elevated VLCFA levels, brain magnetic resonance imaging(MRI) findings, and genetic analysis. Notably, a deletion mutation in Exon 10 of the ABCD1 gene was identified in one case for the first time. We report four cases of X-ALD presenting with adrenocortical insufficiency as the initial symptom, and briefly review the relevant literature to analyze the relationship between linical phenotypes and genetic loci, aiming to provide a reference for early diagnosis and treatment of the disease, and to reduce the risk of misdiagnosis and missed diagnosis.

Objective To identify facilitators and barriers to colorectal cancer screening in community healthcare and propose effective implementation strategies.Methods From February to July 2024,a survey based on the consolidated framework for implementation research(CFIR)was conducted in 8 community health centers in Harbin,using purposive and convenience sampling to select 108 nurses and 550 residents.Binary logistic regression was used to analyze factors affecting nurses'screening knowledge and residents'behaviors.Semi-structured interviews with 21 nurses and 23 residents were analyzed using inductive-deductive methods.Results In the innovation domain,clear goals and free screening facilitated the implementation,while complex processes and resource shortages were barriers.Externally,policy support,funding,and collaboration promoted the screening,but funding gaps and poor communication hindered it.Internally,organizational culture and leadership were positive,while nurse training and teamwork were insufficient.Mixed-method results showed that motivation,ability,opportunity,and needs of nurses and residents significantly impacted screening.Regular feedback and teamwork aided the implementation,but complexity and communication gaps remained obstacles.Conclusion This study analyzed the facilitators and barriers to the screening implementation from the perspectives of community nurses and participants.Recommendations include simplifying processes,optimizing tools and policies,strengthening nurse training and health education,improving communication feedback,and improve outcomes,thereby increasing the participation rate of residents in colorectal cancer screening.

Objective To identify facilitators and barriers to colorectal cancer screening in community healthcare and propose effective implementation strategies.Methods From February to July 2024,a survey based on the consolidated framework for implementation research(CFIR)was conducted in 8 community health centers in Harbin,using purposive and convenience sampling to select 108 nurses and 550 residents.Binary logistic regression was used to analyze factors affecting nurses'screening knowledge and residents'behaviors.Semi-structured interviews with 21 nurses and 23 residents were analyzed using inductive-deductive methods.Results In the innovation domain,clear goals and free screening facilitated the implementation,while complex processes and resource shortages were barriers.Externally,policy support,funding,and collaboration promoted the screening,but funding gaps and poor communication hindered it.Internally,organizational culture and leadership were positive,while nurse training and teamwork were insufficient.Mixed-method results showed that motivation,ability,opportunity,and needs of nurses and residents significantly impacted screening.Regular feedback and teamwork aided the implementation,but complexity and communication gaps remained obstacles.Conclusion This study analyzed the facilitators and barriers to the screening implementation from the perspectives of community nurses and participants.Recommendations include simplifying processes,optimizing tools and policies,strengthening nurse training and health education,improving communication feedback,and improve outcomes,thereby increasing the participation rate of residents in colorectal cancer screening.

X-linked adrenoleukodystrophy(X-ALD) is an inherited progressive neurometabolic disorder caused by mutations in the ATP-binding cassette subfamily D member 1(ABCD1) gene. The encoded ALD protein dysfunction leads to the accumulation of very-long-chain fatty acids(VLCFA). X-ALD is classified according to its clinical characteristics into childhood cerebral ALD, adolescent cerebral ALD, adult cerebral ALD, adrenomyeloneuropathy(AMN), pure adrenocortical insufficiency, and an asymptomatic phenotype, all of which can present with a variety of neurologic manifestations. In this study, we retrospectively analyzed the clinical manifestations, laboratory findings, genetic test results, and follow-up data of four patients with X-ALD, and investigated the clinical features and pathogenicity of the identified gene mutations. All four patients initially presented with adrenocortical insufficiency(Addison′s disease) and received glucocorticoid replacement therapy. Subsequently, all developed neurologic signs and symptoms with rapid progression. The final diagnosis was confirmed based on elevated VLCFA levels, brain magnetic resonance imaging(MRI) findings, and genetic analysis. Notably, a deletion mutation in Exon 10 of the ABCD1 gene was identified in one case for the first time. We report four cases of X-ALD presenting with adrenocortical insufficiency as the initial symptom, and briefly review the relevant literature to analyze the relationship between linical phenotypes and genetic loci, aiming to provide a reference for early diagnosis and treatment of the disease, and to reduce the risk of misdiagnosis and missed diagnosis.

Objective:To investigate the association of muscle mass loss with atherosclerosis in elderly patients with type 2 diabetes mellitus(T2DM).Methods:A total of 322 patients with T2DM aged≥60 years old were divided into muscle mass loss group( n=152) and non-muscle mass loss group( n=170) according to their appendicular skeletal muscle mass index(ASMI). All participants underwent physical examination, dual-energy X-ray absorptiometry check, carotid and lower extremity ultrasound, as well as laboratory tests. Results:Among 322 patients, 49(15.22%) patients were suffered from sarcopenia and 152(47.2%) patients with reduced muscle mass. The carotid and lower extremity atherosclerosis grades in the muscle mass loss group were significantly higher than those in the non-muscle mass loss group( P<0.05), with lower body mass index(BMI), T-score, ASMI, uric acid, and homeostasis model assessment of insulin resistance index( P<0.05). Multivariate logistic regression analysis showed that carotid atherosclerosis and lower extremity atherosclerosis were risk factors for muscle mass loss while BMI and 25-(OH)D 3 were protective factors for muscle mass loss. There existed a consistency in carotid atherosclerosis grade and lower extremity atherosclerosis grade of elderly patients with T2DM( P<0.01). Conclusion:Atherosclerosis has a predictive value for early sarcopenia in elderly patients with T2DM.

Objective:To analyze the gene variants in patients with primary distal renal tubular acidosis (dRTA), and explore the correlation between the genotype and phenotype.Methods:The Sanger direct sequencing or whole-exome sequencing was used to identify causal variants and the variation pathogenicity was evaluated according to 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines in 44 dRTA patients (37 families) diagnosed in the Affiliated Qingdao Municipal Hospital of Qingdao University and the Affiliated Hospital of Qingdao University from April 2010 to September 2020. The clinical features of the patients were summarized, and the correlation between the genotype and phenotype was investigated.Results:Seven variants of SLC4A1 gene, 17 variants of ATP6V0A4 gene, and 15 variants of ATP6V1B1 gene were identified in 44 patients with dRTA, and of which 11 variants were new ones. According to ACMG guidelines, the pathogenic, likely pathogenic, benign variants among the 39 variants were 22, 16 and 1, respectively. Nine patients were autosomal dominant hereditary dRTA caused by SLC4A1 gene mutation, 4 patients with autosomal recessive hereditary dRTA complicated with Southeast Asian ovalocytosis and anemia were caused by SLC4A1 gene mutation, and 14 patients caused by ATP6V0A4 gene mutation and 8 patients caused by ATP6V1B1 gene mutation were autosomal recessive hereditary dRTA; Two children with dRTA were found to carry one monoallelic defect in ATP6V1B1, and no causal gene mutation was identified in 7 patients. One patient showed incomplete dRTA, and the other 43 patients showed complete dRTA. The prevalence of sensory neural hearing loss caused by ATP6V0A4 and ATP6V1B1 mutation were 2/14 and 6/10 respectively. The frequency of chronic kidney disease in adults, children and infants were 4/4, 2/4, and 1/36, separately. After the drug treatment based on potassium citrate and sodium citrate, the growth and development (28/40) and electrolyte disturbance (41/44) of most patients were significantly improved. Conclusions:The present study has identified 39 variants of SLC4A1, ATP6V0A4 and ATP6V1B1 genes in 44 patients with dRTA, including 11 novel ones. There is a close relationship between genotype and phenotype in dRTA patients and most patients' conditions were improved after proper treatment. This study enriches the human gene mutation database and provides valuable references for diagnosis, treatment and genetic counseling in patients with dRTA.

Objective:To explore the related factors of muscle mass loss in patients with type 2 diabetes mellitus, and to provide evidence for prevention of sarcopenia in type 2 diabetic patients.Methods:A cross-sectional survey was used to select type 2 diabetic patients admitted to the Department of Endocrinology, Affiliated Hospital of Qingdao University from January 2019 to August 2019. All subjects underwent dual-energy X-ray absorptiometry check. According to the diagnostic criteria of the Asian Working Group for Sarcopenia (AWGS), the subjects were divided into a muscle reduction group and a non-muscle reduction group. Data including age, gender, body mass index, course of disease, blood index, urinary albumin-creatinin ration (UACR), and appendicular skeletal muscle index (ASMI) were collected. The relevant clinical data of viscera fat/subcutaneous fat (VAT/SAT), percentage of abdominal fat/percentage of hip fat (A/G), grip strength, and pace were analyzed for the related factors of muscle mass loss in type 2 diabetic patients.Results:A total of 369 patients with type 2 diabetes were enrolled, including 42 patients with sarcopenia (an incidence rate of 11.38%), and 155 patients with reduced muscle mass (an incidence of 42.01%). Age, systolic blood pressure, high density lipoprotein-cholesterol, UACR, VAT/SAT, and A/G in the muscle reduction group were higher than those in the non-muscle reduction group ( P<0.05). The parameter of body mass index, homeostasis model assessment for insulin resistance, estimated glomerular filtration rate (eGFR), ASMI, and grip strength were lower in the muscle reduction group than in the non-muscle reduction group ( P<0.05). Multivariate logistic regression analysis showed age, UACR, A/G, and VAT/SAT were risk factors for muscle loss, body mass index, eGFR, and grip strength were protective factors for muscle mass reduction. Conclusion:It is of great practical significance for type 2 diabetic patients, especially those with advanced age, central obesity, low body mass index, low grip strength, low glomerular filtration rate, and high UACR to perform an early screening and to begin an early intervention.

OBJECTIVEOur objective is to build a model that explains the association between the exposure to trace elements in the soil and the risk of neural tube defects.

METHODSWe built a function with different parameters to describe the effects of trace elements on neural tube defects. The association between neural tube defects and trace element levels was transformed into an optimization problem using the maximum likelihood method.

RESULTSTin, lead, nickel, iron, copper, and aluminum had typical layered effects (dosage effects) on the prevalence of neural tube defects. Arsenic, selenium, zinc, strontium, and vanadium had no effect, and molybdenum had one threshold value that affected the prevalence of birth defects.

CONCLUSIONAs an exploratory research work, our model can be used to determine the direction of the effect of the trace element content of cultivated soil on the risk of neural tube defects, which shows the clues by the dosage effect of their toxicological characteristics. Based on our findings, future biogeochemical research should focus on the direct effects of trace elements on human health.

China ; epidemiology ; Dose-Response Relationship, Drug ; Environmental Exposure ; Female ; Humans ; Metals ; chemistry ; toxicity ; Models, Biological ; Neural Tube Defects ; chemically induced ; epidemiology ; Pregnancy ; Prevalence ; Soil Pollutants ; chemistry ; toxicity ; Trace Elements ; chemistry ; toxicity