Clinical-DNA Correlates of Anxiety in Patients with Ehlers-Danlos Syndrome

Introduction: Anxiety disorders have a lifetime prevalence of 34% with a similar level of heritability (31%) yet lack objective markers that could differentiate patients with underlying conditions. Up to 60%-70% of patients with Ehlers-Danlos syndrome have anxiety that meets criteria of generalized anxiety disorder, their clinical-DNA findings worth examining as biomarkers for patients with generalized anxiety. Method: Of the 1899 patients diagnosed with Ehlers-Danlos syndrome, 1261 were systematically evaluated for 80 history and 40 physical findings and separated into 826 who reported anxiety and 435 who did not. The most consistently reported or management-directing 60 of these clinical findings were, along with variations in genes relevant to these disorders, examined for association with anxiety. Results: Among the 30 anxiety- associated findings judged most predictive of Ehlers-Danlos syndrome in patients with anxiety were expected ones of adrenergic stimulation (difficulty concentrating-87% frequency and 1.26 anxiety/no anxiety ratio;chronic fatigue-84%, 1.17;sleep issues 69%, 1.52 that are criteria for generalized anxiety disorder) or of cholinergic suppression (e.g., frequent nausea 64%, 1.26). Less associated but more discriminating for underlying disease were those reflective of neuromuscular impact (e.g., chronic daily headaches 76%, 1.12);hypermobility (e.g., awareness of flexibility 72%, 1.03), or skin changes (e.g., elasticity around jaw 71%, 1.06). Anxiety-associated DNA variants included 54 of 88 in collagen type I/V/VII/IX genes, 14 of 16 in sodium channel SCN9A/10A/ 11A genes, 59 of 85 in POLG/MT-DNA genes, and 21 of 28 in profilaggrin- FLG genes that respectively impacted tissue laxity, sensory neural, autonomic-mitochondrial, and autonomic-inflammatory functions. Conclusion: Analysis of pathogenetic mechanisms in Ehlers-Danlos syndrome selected some 50 clinical-DNA findings useful for its diagnosis in those with generalized anxiety disorders.

Genomic Analysis of 727 Patients with Ehlers-Danlos Syndrome I: Clinical Perspective Relates 23 Genes to a Maternally Influenced Arthritis-Adrenaline Disorder

A novel medical approach for qualifying DNA variants found by whole exome sequencing (WES) facilitates discovery of new gene-disease relationships and emphasizes that DNA change must be correlated with clinical findings before having utility for diagnosis. Delineation of an arthritis-adrenaline disorder (AAD) process qualified variants in 23 genes as diagnostically useful in 727 patients having WES among 1656 with Ehlers-Danlos syndrome (EDS);these results distinguished them from 102 patients who had qualified gene variants among 728 with developmental disability. Excess maternal transmission of AAD by pedigree analysis plus 167 maternally versus 111 paternally transmitted DNA variants and 75 patients with only mitochondrial DNA variants suggest maternal influence on inheritance of AAD and its subsumed EDS types. Genes grouped by impact on different connective tissue elements showed variation in similar numbers of patients with hypermobile or classical EDS, benign joint hypermobility, or predominant dysautonomia: COL7A1, FLG acting on skin in 21 patients;SCN9A/10A/11A, POLG on nerve in 24;COL6A1/A2/A3, COL12 on muscle in 19;COL5A1/A2, FBN1, TGFB2/3, TGFBR1/2 on tissue matrix in 51;COL3A1, VWF on vessel in 18;COL1A1/A2, COL11A1/A2 acting on bone in 15 patients. Each gene group acts through a postulated articulo-autonomic dysplasia cycle to produce reciprocal tissue laxity and dysautonomia findings that transcend EDS types. This same tissue laxity-dysautonomia cycle acts to produce secondary complications in disorders ranging from distinctive connective tissue dysplasias to developmental disorders with hypotonia and acquired conditions with autonomic imbalance. Several altered genes were previously associated with neuromuscular disorders, foreshadowing a large myopathic EDS category that will incorporate many patients with hypermobility. The importance of muscle for joint constraint supports present exercise and future mesenchymal stem cell therapies, whether AAD is genetic or epigenetic from trauma, surgery, inflammation, or aging.

Successful coil embolization with a basic technique for ruptured posterior tibial artery in a patient with Ehlers-Danlos syndrome type IV: A case report

The surgical management of vascular complication with Ehlers-Danlos Syndrome type IV (EDS-IV) is extremely challenging because of its tissue or organ fragility including arteries. Less traumatic maneuvers and devices have been recommended to perform the endovascular treatment for the vascular lesion of EDS-IV, although the endovascular procedure is less invasive than surgical intervention. We report a 23-year-old man with EDS-IV suffered from left posterior tibial arterial rupture. We performed internal trapping of the ruptured segment using detachable coils with a standard technique via the contralateral femoral artery puncture. The patient was discharged without any complication associated with the endovascular procedure. Embolization by a basic technique, performed with greatest care, is a safe and useful treatment option which we radiologists should try for managing EDS-IV patients.

Conservative management of small bowel perforation in Ehlers-Danlos syndrome type Ⅳ

Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders caused by collagen synthesis defects. EDS type Ⅳ, or vascular EDS, is caused by loss-of-function mutations in the type Ⅲ pro-collagen gene (COL3A1 ). Common complications of EDS type IV include gastrointestinal bleeding and bowel perforations, posing diagnostic and therapeutic dilemmas for both surgeons and gastroenterologists. Here, we describe a complicated case of EDS type Ⅳ in a 35-year-old caucasian female who presented with overt gastro-intestinal bleeding. The patient had a prior history of spontaneous colonic perforation, and an uncomplicated upper endoscopy was performed. A careful ileoscopy was terminated early due to tachycardia and severe ab-dominal pain, and a subsequent computed tomography scan confirmed the diagnosis of ileal perforation. The patient was managed conservatively, and demonstrated daily improvement. At the time of hospital discharge, no further episodes of gastrointestinal blood loss had occurred. This case highlights the benefit of conservative management for EDS patients with gastrointestinal hemorrhage. It is recommended that surgical treatmentshould be reserved for patients who fail conservative treatment or in cases of hemodynamic instability. Finally, this case demonstrates the necessity for a higher threshold of operative or endoscopic interventions in EDS type Ⅳ patients.

Clinical Analysis Supports Articulo-Autonomic Dysplasia as a Unifying Pathogenic Mechanism in Ehlers-Danlos Syndrome and Related Conditions

Findings in 1656 patients referred for evaluation of Ehlers-Danlos syndrome, 710 evaluated systematically using novel history and physical forms, defined a characteristic clinical pattern termed arthritis-adrenaline disorder, a genus that provides immediate therapy while delineation of particular tissue laxity/dysautonomia species is underway. Preliminary diagnoses, clinical findings, and laboratory results were entered into an MS Excel? database with IRB approval and correlations or statistical significance analyzed using Excel? functions. Frequencies of 80 findings by history and 40 on physical were similar among EDS groups, females paralleling males with more total history (35 versus 23) and physical (18 versus 15) findings. Finding frequencies in joint-skeletal (6.2 of 15) and dysautonomia (11 of 20) subcategories were substantial regardless of age, EDS diagnosis, or referral source, the latter was shown by 6.4 and 13 average findings for cardiology, 5.3 and 8.3 for orthopedic referrals. Early affliction evidenced by history findings averaging 19.5 in those under 12 increased dramatically to 25 for teens and 32 for adults with plateauing at older ages arguing against degenerative disease. Frequent neuromuscular symptoms in females emphasize surrounding muscle support and protection of joint-connective tissue as a key factor in decreased male severity. The congruent clinical profile suggests operation of an articulo-autonomic dysplasia cycle where lax vessels and lower body pooling elicit sympathetic response, autonomic imbalance in turn affecting small nerve fibers and enhancing connective tissue laxity. Recognition of this arthritis-adrenalin disorder can guide management strategies while underlying causes are pursued, among them, physical therapy, exercise, and vitamin D to build muscle/bone strength;lower gluten/dairy and antihistamine protocols for low bowel motility/mast-cell activation;hydration, salt, and exercise for postural orthostatic tachycardia syndrome.

Anterior cervical corpectomy decompression and fusion for cervical kyphosis in a girl with Ehlers-Danlos syndrome:A case report

BACKGROUND Spinal deformities in Ehlers-Danlos syndrome(EDS; type VI) are generally progressive and severe. Surgical treatment has been described for kyphoscoliosis in the thoracolumbar spine. However, there are few studies describing the consequences of an anterior approach in cervical kyphosis. An anterior approach may not be able to fully decompress the spinal canal and restore the normal curvature of the cervical spine. Therefore, the anterior approach for cervical kyphosis in young children is hard. We describe the first case in an EDS girl with cervical kyphosis who received satisfactory anterior cervical corpectomy decompression and fusion.CASE SUMMARY The chief complaints of a 16-year-old girl with EDS were double upper limb weakness for 7 years and double lower limb walking instability for 2 years.Moreover, the imaging results revealed that the degree of kyphosis from cervical vertebra 2 to 4 accompanying with spinal cord compression was 30°. An anterior cervical corpectomy involving cervical vertebra 3 and a titanium mesh implant were performed with internal fixation. The results at 3 mo after surgery demonstrated that the anterior fusion was solid, and the kyphosis of the cervical spine was corrected. Additionally, the power of all four extremities was significantly improved.CONCLUSION The incidence rate of cervical kyphosis in EDS is rare. The surgical treatment for these patients, especially an anterior approach, is challenging. Therefore, to develop safer and more effective strategies to treat cervical kyphosis in EDS,there is still much work to do.

SURGICAL MANAGEMENT OF EHLERS-DANLOS SYNDROME:FIRST REPORT OF A PEDIGREE IN CHINA

OBJECTIVE: To describe a case of Ehlers-Danlos syndrome type IV and its pedigree in China. METHODS: Clinical materials of a case of Ehlers-Danlos syndrome type IV and a pedigree of 6 members within 4 generations were analyzed. Dilated internal jugular vein in the proband was removed by operation. The diagnosis, surgical treatment, and postoperative complications were retrospectively reviewed. RESULTS: Vessels of the proband in the pedigree were crisp and easily lacinated during the procedure of removing his internal jugular vein. Repeating postoperative hematomas were found though complete stanching was achieved during the operation. The patient was successfully recovered by promptly debridgement and needle sucking. The other 5 members of the pedigree all had the triads of Ehlers-Danlos syndrome. CONCLUSIONS: Though it was of extremely low morbidity rate, the high mortality rate and complication of Ehlers-Danlos syndrome deserve great attention during surgical management, especially in patients with Ehlers-Danlos syndrome type IV. Surgeons should be aware of the ponderance of its complications and combined diseases to avoid fatal intraoperative vascular lascination and incontrollable hemorrhage.

Classic Ehlers-Danlos syndrome and cardiac transplantation-Is there a connection?

Ehlers-Danlos syndrome(EDS)is a heterogeneous group of connective tissue disorders comprised of several types.Classic EDS is an autosomal dominant disorder with stretchable skin,delayed wound healing with poor scarring,joint hypermobility with subluxations or dislocations,easy bruisability,hernias,aneurysms and cardiac abnormalities.Advances in genomics technology using next-generation sequencing has led to the discovery of causative genes for connective tissue disorders,hereditary cardiomyopathies and cardiovascular diseases including several genes for connective tissue disorders.A 55 year-old male exhibited thin stretchable skin,atrophic scars,easy bruising,joint pain and dislocations requiring multiple knee surgeries and a Beighton hyperflexibility score of 6 out of 7.He was found to have a heterozygous missense COL5A1 gene variant involving exon 3 at nucleotide c:305T>A with an amino acid position change at p.lle102Asn consistent with classic EDS.He had a heart transplant at 43 years of age due to cardiac failure of unknown cause.This patient with classic EDS is brought to medical attention and should be of interest to cardiologists,heart transplant specialists and surgeons,particularly in individuals with unexplained cardiac failure and then diagnosed prior to surgical intervention to avoid poor wound healing,scarring and other tissue involvement(e.g.,vascular anomalies,blood pressure instability,aneurysms)as components of EDS.

Mutation in TNXB gene causes moderate to severe Ehlers-Danlos syndrome

We report a 28-year-old female who presented with severe joint pain, chronic muscle weakness, Raynaud’s phenomenon, and hypermobility. She was found to have a 6074A 〉 T nucleotide transition in the TNXB gene causing an amino acid protein change at Asp2025Val classifed as likely pathogenic. We add this clinical report to the literature and classical human disease gene catalogs to identify this specific mutation as disease-causing. This gene variant was reported previously in a different 36-year-old patient who shared our patient’s symptoms of joint hypermobility, skeletal and joint pain, skin elasticity and musculoskeletal problems, thereby causing a more severe presentation than seen in the hypermobility type of Ehlers-Danlos syndrome （EDS）. At the time of writing, a few mutations in the TNXB gene have been recognized as pathogenic causing EDS due to tenascin-X defciency, but the variant identifed in our patient has not been recognized as pathogenic in online genetic databases. Our case study in combination with peer-reviewed literature suggests that the 6074A 〉 T nucleotide transition in the TNXB gene may be classifed as disease-causing for EDS due to tenascin-X defciency.

Complement Gene Mutation and Ehlers-Danlos Syndrome

Background: Dental complications of Ehlers-Danlos syndrome (EDS) include periodontitis with gum fragility and inflammation, enamel hypoplasia with frequent caries, high palate with dental crowding, TMJ instability, sutural dehiscence or scarring, and insensitivity to anesthetics. Objective: Determine if EDS dental complications always define a specific type and genetic cause or if they can arise as a general consequence of altered inflammatory response in EDS. Method: We compared findings of a 58-year-old female with complement component 1R (C1R) gene mutation (c.1553A > T, p.Asp518Val) found by whole exome sequencing to 43 patients with C1R gene mutations ascertained because of periodontal disease and to 710 EDS patients conventially ascertained because of joint and skin laxity. Result: Female patients ascertained as periodontal EDS showed the expected higher frequency of periodontitis (96% versus 14%) but had similar frequencies of hypermobility (81% versus 90%) and some skin findings (84% versus 92% with skin fragility) as the general group and our female patient who shared their C1R gene change. Her oromandibular bone loss rather than gum disease may reflect the more carboxy-terminal position of her C1R gene mutation compared to those in the patients identified as periodontal EDS. Conclusion: While mutation of the C1R gene may predict more frequent periodontal, skin, and vascular complications, focus on an articulo-autonomic dysplasia process that includes mast-cell activation and altered inflammatory response rather than extreme EDS types will help dentists and other subspecialists identify all EDS patients and anticipate their frequent oral manifestations.

Predictive value of alarm symptoms in Rome IV irritable bowel syndrome:A multicenter cross-sectional study

BACKGROUND Irritable bowel syndrome(IBS)is a common functional bowel disease that shares features with many organic diseases and cannot be accurately diagnosed by symptom-based criteria.Alarm symptoms have long been applied in the clinical diagnosis of IBS.However,no study has explored the predictive value of alarm symptoms in suspected IBS patients based on the latest Rome IV criteria.AIM To investigate the predictive value of alarm symptoms in suspected IBS patients based on the Rome IV criteria.METHODS In this multicenter cross-sectional study,we collected data from 730 suspected IBS patients evaluated at 3 tertiary care centers from August 2018 to August 2019.Patients with IBS-like symptoms who completed colonoscopy during the study period were initially identified by investigators through medical records.Eligible patients completed questionnaires,underwent laboratory tests,and were assigned to the IBS or organic disease group according to colonoscopy findings and pathology results(if a biopsy was taken).Independent risk factors for organic disease were explored by logistic regression analysis,and the positive predictive value(PPV)and missed diagnosis rate were calculated.RESULTS The incidence of alarm symptoms in suspected IBS patients was 75.34%.Anemia[odds ratio(OR)=2.825,95%confidence interval(CI):1.273-6.267,P=0.011],fecal occult blood[OR=1.940(95%CI:1.041-3.613),P=0.037],unintended weight loss(P=0.009),female sex[OR=0.560(95%CI:0.330-0.949),P=0.031]and marital status(P=0.030)were independently correlated with organic disease.The prevalence of organic disease was 10.41%in suspected IBS patients.The PPV of alarm symptoms for organic disease was highest for anemia(22.92%),fecal occult blood(19.35%)and unintended weight loss(16.48%),and it was 100%when these three factors were combined.The PPV and missed diagnosis rate for diagnosing IBS were 91.67%and 74.77%when all alarm symptoms were combined with Rome IV and 92.09%and 34.10%when only fecal occult blood,unintended weight loss and anemia were combined with Rome IV,respectively.CONCLUSION Anemia,fecal occult blood and unintended weight loss have high predictive value for organic disease in suspected IBS patients and can help identify patients requiring further examination but are not recommended as exclusion criteria for IBS.

司美格鲁肽对2型糖尿病合并多囊卵巢综合征患者血清超敏C反应蛋白及IV型胶原蛋白的影响

目的:探讨司美格鲁肽对2型糖尿病(T2DM)合并多囊卵巢综合征(PCOS)患者血清超敏C反应蛋白(hs-CRP)及IV型胶原蛋白(Col IV)的影响。方法:选取30例初诊T2DM合并PCOS患者为研究对象,给予司美格鲁肽治疗16周。分析比较患者治疗前后血糖、血脂、体重、性激素相关指标及hs-CRP和Col IV的变化,并探究司美格鲁肽治疗后hs-CRP与各指标的相关性。结果:治疗16周后,受试者空腹血糖(FBG)、餐后2 h血糖(2hBG)、糖化血红蛋白(HbA1C)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、腰围(WC)、体质量指数(BMI)、甘油三酯(TG)、胆固醇(TC)、黄体生成素(LH)、LH/FSH、总睾酮(TT)、hs-CRP、Col IV均较治疗前降低,卵泡刺激素(FSH)较治疗前升高,差异均有统计学意义(P<0.05)。司美格鲁肽治疗后hs-CRP与BMI、WBC、HbA1c、FBG、2hBG、FINS、TG、Col IV正相关(P<0.05)。结论:司美格鲁肽既能改善T2DM合并PCOS患者的血糖、血脂、体重、胰岛素抵抗、性激素,也能改善机体的炎症状态及卵巢纤维化,其可能是T2DM合并PCOS患者的潜在治疗靶点。

Clinical Syndromes Associated with Cardiovascular Diseases:A Review

In clinical practice,a variety of syndromes are associated with cardiovascular disease and have characteristic findings.Most of them are an autosomal dominant genetic disorder and have different types of cardiovascular abnormalities,including electrocardiographic conduction defects,arrhythmias,cardiomyopathy,vascular and valvular diseases,cardiac septal defects,and pulmonary problems.There is a growing need for physicians to pay more attention to these syndromes.

Homozygous factor Ⅴ Leiden mutation in type Ⅳ Ehlers-Danlos patient

Ehlers-Danlos syndrome(EDS) is a group of inherited connective tissue disorders caused by collagen synthesis defects. Several hemostatic abnormalities have been described in EDS patients that increase the bleeding tendencies of these patients. This case report illustrates a patient with an unusual presentation of a patient with type Ⅳ EDS, platelet δ-storage pool disease and factor Ⅴ Leiden mutation. Young woman having previous bilateral deep vein thrombosis and pulmonary emboli coexisting with ruptured splenic aneurysm and multiple other aneurysms now presented with myocardial infarction. Presence of factor Ⅴ Leiden mutation raises the possibility that the infarct was due to acute coronary thrombosis, although coronary artery aneurysm and dissection with myocardial infarction is known to occur in vascular type EDS. This is the first report in the medical literature of factor Ⅴ Leiden mutation in an EDS patient which made the management of our patient challenging with propensity to both bleeding and clotting.

Demon Genes May Deform Common Syndromes: Collagen VI Gene Change in Down Syndrome Unifies the Medical and Molecular Approach to Hypermobility Disorders

Purpose: To alert the medical community that whole exome sequencing can find accessory gene changes in well-known syndromes that alter preventive health care and management. Meaning: A collagen type VI gene change adds muscle weakness, hypermobility, and dysautonomia concerns to usual management considerations for Down syndrome. Methods: Commercial whole exome sequencing combined with clinical interpretation of DNA sequence change added new considerations to patient management and parental counsel. Results: An 11-year-old child with the trisomy 21 form of Down syndrome who was evaluated for extraordinary joint laxity had a heterozygous collagen type VI aspartic to glutamic acid (COL6A3 c.6360 C>G p.Asp2120Glu) gene change found by whole exome sequencing. The DNA variant was qualified as having strong relevance to the enhanced hypermobility due to prior association of collagen 6 gene changes with myopathy. Conclusions: Dual diagnosis of Ehlers-Danlos syndrome was not assigned because the patient lacked criteria like bruising, unusual scars, or selected dysautonomia symptoms. The concept of a hypermobility spectrum offers advantages for management of its constituent conditions if clinically guided ascertainment and DNA diagnostics are employed.

IV型胶原蛋白相关听力损失的研究进展

IV型胶原蛋白是基底膜等组织的重要组成成分,广泛存在于肾脏、耳蜗等人体器官中。相比引起如肾脏等器官的疾病而言,国内外研究对IV型胶原蛋白相关听力损失的关注相对较少。本文旨在总结已报道的部分IV型胶原蛋白亚型与听力损失相关疾病的研究进展,为后续相关研究提供研究方向参考。

不同分型的多囊卵巢综合征患者IVF-ET后的妊娠结局

目的探讨行体外受精-胚胎移植(IVF-ET)后不同分型的多囊卵巢综合征(PCOS)患者的妊娠结局。方法选择接受IVF-ET治疗并成功妊娠的PCOS妇女160例,及输卵管因素妇女350例进行回顾性分析,以身体质量指数(BMI)≥或<24kg/m^2为界线分为4组:肥胖PCOS组28例(A组),非肥胖PCOS组132例(B组),肥胖输卵管因素组41例(C组),非肥胖输卵管因素组309例(D组)。分析各组的临床特征、IVF参数、妊娠及围产儿结局。结果 4组间的年龄、BMI、原发性不孕比例、不孕年限、基础促卵泡生成素(FSH)水平的差异均有统计学意义(t=12.603,P=0.031;t=21.619,P=0.000;χ~2=78.681,P=0.000;t=7.838,P=0.045;t=16.264,P=0.020)。B纽的人绒毛膜促性腺激素(hCG)日雌二醇(E_2)水平最高、获卵数最多,其次是A组,均多于输卵管因素组(C和D组),差异均有统计学意义(t=28.581,P=0.000;t=25.492,P=0.000);PCOS组(A和B组)的受精率、优胚数、移植率比输卵管因素组(C和D组)低,差异均有统计学意义(t=21.642,P=0.000;t=9.863,P=0.035;χ~2=27.711,P=0.000)。肥胖组(A和C组)妊娠期糖尿病的发病率及大于胎龄儿发生率比非肥胖组(B和D)高,差异均有统计学意义(χ~2=14.698,P=0.002;χ~2=25.003,P=0.000);PCOS组(A和B组)小于胎龄儿的发生率高于输卵管因素组(C和D组),差异均有统计学意义(χ~2=8.086,P=0.044)。结论在接受IVF-ET治疗的不同类型PCOS妇女中,非肥胖与肥胖PCOS的IVF参数、妊娠结局及围产儿结局有些不同,肥胖PCOS的获卵数少于非肥胖PCOS,妊娠期糖尿病和巨大儿的发生率增加,但不影响其临床妊娠率。

Connecting brain and body:Transdiagnostic relevance of connective tissue variants to neuropsychiatric symptom expression

The mind is embodied;thoughts and feelings interact with states of physiological arousal and physical integrity of the body.In this context,there is mounting evidence for an association between psychiatric presentations and the expression variant connective tissue,commonly recognised as joint hypermobility.Joint hypermobility is common,frequently under-recognised,significantly impacts quality of life,and can exist in isolation or as the hallmark of hypermobility spectrum disorders(encompassing joint hypermobility syndrome and hypermobile Ehlers-Danlos syndrome).In this narrative review,we appraise the current evidence linking psychiatric disorders across the lifespan,beginning with the relatively well-established connection with anxiety,to hypermobility.We next consider emerging associations with affective illnesses,eating disorders,alongside less well researched links with personality disorders,substance misuse and psychosis.We then review related findings relevant to neurodevelopmental disorders and stress-sensitive medical conditions.With growing understanding of mind-body interactions,we discuss potential aetiopathogenetic contributions of dysautonomia,aberrant interoceptive processing,immune dysregulation and proprioceptive impairments in the context of psychosocial stressors and genetic predisposition.We examine clinical implications of these evolving findings,calling for increased awareness amongst healthcare professionals of the transdiagnostic nature of hypermobility and related disorders.A role for early screening and detection of hypermobility in those presenting with mental health and somatic symptoms is further highlighted,with a view to facilitate preventative approaches alongside longer-term holistic management strategies.Finally,suggestions are offered for directions of future scientific exploration which may be key to further delineating fundamental mind-body-brain interactions.

非酒精性脂肪肝患者血清HA、PC-Ⅲ、Ⅳ-C水平变化及其与中医证型的关系

目的探究非酒精性脂肪肝(non-alcoholic fatty liver disease,NAFLD)患者血清透明质酸(hyaluronic acid,HA)、Ⅲ型前胶原(typeⅢprocollagen,PC-Ⅲ)、Ⅳ型胶原(typeⅣcollagen,Ⅳ-C)水平变化及其与中医证型的关系。方法选取2018年10月—2019年2月医院收治的66例NAFLD患者为研究对象,依照病情严重程度将患者分为轻度组(25例)、中度组(21例)、重度组(20例),并选择同期正常健康体检者35例作为对照组,检测全部受试对象血清HA、PC-Ⅲ、Ⅳ-C水平,并进行中医辨证分型,比较各组血清HA、PC-Ⅲ、Ⅳ-C水平,并分析上述血清指标与中医证型的关系。结果各组血清HA、PC-Ⅲ、Ⅳ-C水平比较差异具有统计学意义(P<0.05),且轻度组、中度组、重度组均高于对照组,中度组、重度组均高于轻度组,重度组高于中度组(P<0.05);根据中医诊断标准,辨证为痰浊内阻证14例(21.21%);湿热蕴结证17例(25.76%);脾肾两虚证18例(27.27%);痰瘀互结证17例(25.76%);中医不同证型NAFLD患者血清HA、PC-Ⅲ、Ⅳ-C水平比较,差异有统计学意义(P<0.05);痰瘀互结证患者上述血清指标高于其他证型(P<0.05)。结论血清HA、PC-Ⅲ、Ⅳ-C水平能反映NAFLD病情严重程度,且对患者的中医辨证分型具有一定的临床指导意义。

Relationship between obstructive sleep apnea-hypopnea syndrome(OSAHS)and liver fibrosis

Objective:The current study discusses the relationship between sleep apnea-hypopnea syn-drome(OSAHS)and liver fibrosis by determining the level of plasma hyaluronic acid(HA),pro-collagen III(PIII),collagen IV(IVC),and laminin(LN)in OSAHS patients and non-OSAHS patients with obesity and normal body weight.Methods:The patients who underwent polysomnographic(PSG)examinations in the outpatient and inpatient departments of our hospital between December 2010 and June 2013 were selected.The patients were divided into two groups based on the apnea-hypopnea index(AHI;OSAHS and non-OSAHS patients),and both groups were further divided based on obesity and normal body weight based on the body mass index(BMI).Sleep breathing indicators,including BMI,AHI,LSaO_(2),and MSaO_(2),were measured in all patients.All of the patients had their blood drawn on the morning after the day of the PSG examination,and the samples were sent to the biochemical laboratory of our hospital for determination of the levels of HA,PIII,IVC,and LN.Results:Among the obese and normoweight patients,the levels of HA,PIII,IVC,and LN in OSAHS patients were higher than the non-OSAHS patients(P value<0.05).Amongst the OSAHS and non-OSAHS patients,the levels of HA,PIII,IVC,and LN in the obese patients were also higher than the non-obese patients(P value<0.05).The levels of HA,PIII,IVC,and LN in the obese OSAHS patients were higher than the remaining three groups(P value<0.05).The levels of HA,PIII,IVC,and LN had positive correlations with the AHI and BMI(r=0.701,0.523,0.639,and 0.421,respectively,P<0.05;and r=0.565,0.441,0.475,and 0.401,respectively,P<0.05),and nega-tive correlations with the LSaO_(2) and MSaO_(2) in OSAHS patients(r=-0.432,-0.394,-0.403,and-0.267,respectively,P<0.05;and r=-0.591,-0.517,-0.533,and-0.484,respectively,P<0.05).Conclusion:The levels of plasma HA,PIII,IVC,and LN in OSAHS patients were related to OSAHS.OSAHS might lead to liver fibrosis.