IoT service composition based on improved Shuffled Frog Leaping Algorithm.

In the complex Internet of Things (IoT) environment, a plethora of IoT services with akin functions but varying qualities of service exist. To meet diverse customer needs and drive widespread application, service composition optimization becomes crucial. In the current era of rapid development in artificial intelligence, intelligent algorithms play a significant role in optimizing service composition. However, algorithms applied to IoT service composition optimization face common challenges of low search efficiency and insufficient optimization precision, including the Shuffled Frog Leaping Algorithm (SFLA) and Genetic Algorithm (GA). Therefore, this study seeks to enhance the perception of service quality in IoT service composition. It proposes an improved SFLA (ISFLA) based on the original SFLA. The algorithm integrates chaos theory and reverse learning theory for the acquisition of the initial population. It utilizes Euclidean distance to partition the population into groups and employs Gaussian mutation to optimize the optimal individual of each group. Finally, the entire population undergoes evolution through a local update method based on two strategies. Simulated experiments were conducted to search for optimal IoT service composition solutions of different scales. The results indicate that, compared to the SFLA, GA, ISFLA*, IGSFLA and SFLAGA, ISFLA achieves superior fitness values, better composition solutions, and exhibits faster convergence, higher stability, and greater overall operational efficiency.

How problem difficulty and order influence programming education outcomes in online judge systems.

With the widespread application of computer technology in engineering education, Online Judge (OJ) systems have become an important platform for programming teaching. OJ systems provide a platform for learners to practice programming skills, submit solutions, and receive feedback. They offer a conducive environment for learners to engage in hands-on coding exercises and enhance their programming abilities. This article explores the use of OJ systems as a software tool for enhancing programming education in engineering. It investigates how the difficulty and order of programming problems affect the users' behavior, performance, and cognitive load in OJ environments. The research data were sourced from Project_CodeNet. Using statistical methods, such as Spearman correlation analysis and differential analysis, the study reveals the factors that influence the users' submission situations, answer order, and learning outcomes. The findings provide useful implications for OJ system developers, teachers, and learners in designing, implementing, and using OJ systems for programming education in engineering. The study suggests that problem difficulty and order should be considered and adjusted according to the users' abilities and progress, to provide appropriate challenges and support, balance the cognitive load, and improve the programming skills of the users.

Clinical Outcomes of Transmetatarsal Amputation in Patients with Diabetic Foot Ulcers Treated without Revascularization.

INTRODUCTION: Most studies on outcomes of transmetatarsal amputation (TMA) have been for patients who underwent revascularization. This study was performed to evaluate the outcomes of TMA in diabetic patients without revascularization. METHODS: One hundred two diabetic patients who were not candidates for revascularization underwent TMA and received a multidisciplinary treatment. These patients were followed up for a mean period of 38 months to observe the outcomes, including wound healing, above-the-ankle amputation and death. The associations between variables and the outcomes were analyzed by Cox regression analysis. RESULTS: By the end of the follow-up, 97 patients with full data were analyzed. Sixty-three (64.9%) patients had wounds healed completely after a median interval of 8 months, 16 (16.5%) patients underwent above-the-ankle amputation, and 26 (26.8%) died. Cox regression analysis showed that patients with higher ABI (RR = 3.097, 95% CI: 1.587-6.043) and serum albumin (RR = 2.755, 95% CI: 1.335-5.687) exhibited a higher probability of wound healing. CONCLUSIONS: Diabetic patients who were not candidates for revascularization who underwent TMA could achieve a satisfactory wound healing rate with a multidisciplinary treatment. ABI and serum albumin were significant predictors of wound healing.

Signature microRNAs and long noncoding RNAs in laryngeal cancer recurrence identified using a competing endogenous RNA network.

The aim of the present study was to identify novel microRNA (miRNA) or long noncoding RNA (lncRNA) signatures of laryngeal cancer recurrence and to investigate the regulatory mechanisms associated with this malignancy. Datasets of recurrent and nonrecurrent laryngeal cancer samples were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus database (GSE27020 and GSE25727) to examine differentially expressed miRNAs (DE­miRs), lncRNAs (DE­lncRs) and mRNAs (DEGs). miRNA­mRNA and lncRNA­miRNA networks were constructed by investigating the associations among these RNAs in various databases. Subsequently, the interactions identified were combined into a competing endogenous RNA (ceRNA) regulatory network. Feature genes in the miRNA­mRNA network were identified via topological analysis and a recursive feature elimination algorithm. A support vector machine (SVM) classifier was established using the betweenness centrality values in the miRNA­mRNA network, consisting of 32 optimal feature­coding genes. The classification effect was tested using two validation datasets. Furthermore, coding genes in the ceRNA network were examined via pathway enrichment analyses. In total, 21 DE­lncRs, 507 DEGs and 55 DE­miRs were selected. The SVM classifier exhibited an accuracy of 94.05% (79/84) for sample classification prediction in the TCGA dataset, and 92.66 and 91.07% in the two validation datasets. The ceRNA regulatory network comprised 203 nodes, corresponding to mRNAs, miRNAs and lncRNAs, and 346 lines, corresponding to the interactions among RNAs. In particular, the interactions with the highest scores were HLA complex group 4 (HCG4)­miR­33b, HOX transcript antisense RNA (HOTAIR)­miR­1­MAGE family member A2 (MAGEA2), EMX2 opposite strand/antisense RNA (EMX2OS)­miR­124­calcitonin related polypeptide α (CALCA) and EMX2OS­miR­124­Î³­aminobutyric acid type A receptor Î³2 subunit (GABRG2). Gene enrichment analysis of the genes in the ceRNA network identified that 11 pathway terms and 16 molecular function terms were significantly enriched. The SVM classifier based on 32 feature coding genes exhibited high accuracy in the classification of laryngeal cancer samples. miR­1, miR­33b, miR­124, HOTAIR, HCG4 and EMX2OS may be novel biomarkers of recurrent laryngeal cancer, and HCG4­miR­33b, HOTAIR­miR­1­MAGEA2 and EMX2OS­miR­124­CALCA/GABRG2 may be associated with the molecular mechanisms regulating recurrent laryngeal cancer.

Interactive biomedical ontology matching.

Due to continuous evolution of biomedical data, biomedical ontologies are becoming larger and more complex, which leads to the existence of many overlapping information. To support semantic inter-operability between ontology-based biomedical systems, it is necessary to identify the correspondences between these information, which is commonly known as biomedical ontology matching. However, it is a challenge to match biomedical ontologies, which dues to: (1) biomedical ontologies often possess tens of thousands of entities, (2) biomedical terminologies are complex and ambiguous. To efficiently match biomedical ontologies, in this paper, an interactive biomedical ontology matching approach is proposed, which utilizes the Evolutionary Algorithm (EA) to implement the automatic matching process, and gets a user involved in the evolving process to improve the matching efficiency. In particular, we propose an Evolutionary Tabu Search (ETS) algorithm, which can improve EA's performance by introducing the tabu search algorithm as a local search strategy into the evolving process. On this basis, we further make the ETS-based ontology matching technique cooperate with the user in a reasonable amount of time to efficiently create high quality alignments, and make use of EA's survival of the fittest to eliminate the wrong correspondences brought by erroneous user validations. The experiment is conducted on the Anatomy track and Large Biomedic track that are provided by the Ontology Alignment Evaluation Initiative (OAEI), and the experimental results show that our approach is able to efficiently exploit the user intervention to improve its non-interactive version, and the performance of our approach outperforms the state-of-the-art semi-automatic ontology matching systems.

Drug repositioning in head and neck squamous cell carcinoma: An integrated pathway analysis based on connectivity map and differential gene expression.

The severe damage to health and social burden caused by head and neck squamous cell carcinoma (HNSCC) generated an urgent need to develop novel anti-cancer therapy. Currently, drug repositioning has risen in responses to the proper time as an efficient approach to invention of new anti-cancer therapies. In the present study, we aimed to screen candidate drugs for HNSCC by integrating HNSCC-related pathways from differentially expressed genes (DEGs) and drug-affected pathways from connectivity map (CMAP). We also endeavored to unveil the molecular mechanism of HNSCC through creating drug-target network and protein-to-protein (PPI) network of component DEGs in key overlapping pathways. As a result, a total of 401 DEGs were obtained from TCGA and GTEx mRNA-seq data. Taking the intersection part of 27 HNSCC-related Kyoto Encyclopedia of Genes and Genomes pathways and 33 drug-affected pathways, we retained 22 candidate drugs corresponding to two key pathways (cell cycle and p53 signaling pathways) of the five overlapping pathways. Two of the hub genes (PCNA and CCND1) identified from the PPI network of component DEGs in cell cycle and p53 signaling pathways were defined as the critical targets of candidate drugs with increased protein expression in HNSCC tissues, which was reported by the human protein atlas (HPA) database and cBioPortal. Finally, we validated via molecular docking analysis that two drugs with unknown effects in HNSCC: MG-262 and bepridil might perturb the development of HNSCC through targeting PCNA. These candidate drugs possessed broad application prospect as medication for HNSCC.

Expression level and prospective mechanism of miRNA-99a-3p in head and neck squamous cell carcinoma based on miRNA-chip and miRNA-sequencing data in 1, 167 cases.

BACKGROUND: The role of miR-99a-3p in Head and neck squamous cell carcinoma (HNSCC) has not been reported. Therefore, in this study, we examined the expression level and its molecular mechanisms of miR-99a-3p in HNSCC. MATERIALS AND METHODS: MiR-99a-3p-related miRNA-chip and miRNA-sequencing data were collected. We then carried out meta-analyses to pool the standard mean difference (SMD) value and generate a summarized receiver operating characteristic (sROC) curve. MiR-99a-3p mimic was transfected into FaDu cells and those genes influenced by miR-99a-3p were gathered. The target genes were also predicted from 12 tools through miRwalk2.0, and combined with differentially expressed genes in HNSCC from the The Cancer Genome Atlas and Genotype-Tissue Expression sequencing databases. FunRich and DAVID were used for the pathway signaling analyses for the potential targets of miR-99a-3p in HNSCC. RESULTS: The SMD was -0.30 (95% CI: -0.51, -0.08) in the fixed-effect model and -0.28 (95% CI: -0.67, 0.10) in the random-effect model (I2 = 60%), indicating a reduced expression level of miR-99a-3p in HNSCC tissues based on 1167 cases. In the sROC curve, the area under the curve (AUC) was 0.77 (95% CI: 0.73, 0.81). The 251 potential targets of miR-99a-3p were enriched in several pathways related to cancer, with the "Pathways in cancer" standing at the top. vascular endothelial growth factor A was selected as an example with up-regulated trend in HNSCC tissues. CONCLUSION: MiR-99a-3p exhibits a significant lower expression status in HNSCC, and this reduced or deletion status promotes the malignant progression of HNSCC. However, its molecular mechanism is still unclear and requires further investigation.

Reasonable Glycemic Control Would Help Wound Healing During the Treatment of Diabetic Foot Ulcers.

INTRODUCTION: The effect of glycemic control on wound healing in patients with diabetic foot ulcers (DFUs) is inconsistent among different studies. This study was performed to investigate the association between level of hemoglobin A1c (HbA1c) at baseline as well as during treatment and wound healing and mortality in patients with DFU. METHODS: Hospitalized DFU patients were recruited consecutively with their basic clinical data collected and treated according to clinical practice guidelines. These patients were followed-up for 1 year to observe the outcomes, including ulcer healing and death. The associations between baseline HbA1c level or mean HbA1c level during treatment and wound healing as well as mortality were evaluated in univariate and multivariate logistic regression models. RESULTS: By the end of the follow-up, 40 (13.4%) patients had died. A total of 168 (65.1%) patients achieved ulcer healing in the remaining 258 living participants. Baseline HbA1c was not associated with ulcer healing in unadjusted or adjusted models (P > 0.05). The wound healing rate was higher (OR 2.01, 95% CI 1.02-3.96, P < 0.05) after adjustment when HbA1c was controlled between 7.0% and 8.0% during treatment compared to HbA1c controlled at less than 7.0%. This probability of ulcer healing increased to 3 (OR = 3.01, 95% CI 1.32-6.86, P = 0.01) after adjustment in the subgroup with baseline HbA1c no more than 8.0%. Neither baseline HbA1c nor mean HbA1c during treatment presented any correlation with 1-year death rate. CONCLUSION: A reasonable HbA1c target, a range between 7.0% and 8.0% during treatment, could facilitate ulcer healing without increase of mortality in patients with DFU, especially for those with better glycemic control at admission.

Association between QTc interval prolongation and outcomes of diabetic foot ulcers: Data from a 4-year follow-up study in China.

OBJECTIVES: To examine whether QTc interval prolongation is an independent risk factor of outcomes in patients with diabetic foot ulcers (DFU). RESEARCH DESIGN AND METHODS: 331 patients with type 2 diabetes and DFU hospitalized in a Chinese tertiary hospital were recruited. ECG was done at baseline and QTc interval was calculated through Bazett's formula. Participants were classified into 2 groups according to the QTc interval as prolonged (≥440 ms) or not (<440 ms). These patients were followed-up for an average of 48 months to observe the outcomes, including ulcer healing, ulcer recurrence, nonfatal cerebral or cardiovascular events (NCCVE), cerebral cardiovascular death, cardiac death and all-cause death. The associations between the risk of outcomes and QTc interval prolongation, as well as per 1-SD increase in QTc interval were analyzed by Cox proportional-hazards models. RESULTS: In terms of the univariate Cox proportional hazard models, patients with QTc interval prolongation had a higher all-cause mortality (HR = 1.621, 95%CI: 1.040-2.526, P = .013), higher cardiac mortality (HR = 2.011 95%CI: 1.106-3.657, P = .019), higher cerebral cardiovascular mortality (HR = 1.525, 95%CI: 0.8151-2.852, P = .045). The multivariate analysis showed that QTc prolongation was an independent risk factor for cardiac death (HR = 5.465, 95%CI: 2.818-8.112, P = .039). Similar results were obtained when QTc interval was used as a continue variable, a 1-SD increase in QTc interval was associated with an 5.883 times risk for cardiac mortality (HR = 6.883, 95%CI: 4.153-9.613, P = .012). The association between QTc interval prolongation with ulcer healing, recurrence and NCCVE were not observed either in univariate or multivariate analysis (P > .05). CONCLUSION: QTc interval prolongation was a plausible predictor for cardiac death in DFU patients, but it cannot accurately predict ulcer healing or recurrence.

Association between estimated glomerular filtration rate and outcomes in patients with diabetic foot ulcers: a 3-year follow-up study.

OBJECTIVE: End-stage renal disease and dialysis have been proven to be associated with poor prognoses in diabetic foot ulcers (DFUs). However, it has rarely been reported whether and to what extent milder renal insufficiency affects the prognosis. The purpose of this study was to investigate the categorized impact of estimated glomerular filtration (eGFR) on the outcomes of patients with DFU. DESIGN AND METHODS: Three hundred and sixty-six DFU patients hospitalized in a Chinese tertiary hospital were recruited and classified into 4 groups according to the eGFRs as follows: normal (≥90), mildly reduced (60-89), moderately reduced (30-59), and severely reduced (<30). These patients were followed-up for an average of 37 months to observe the outcomes, including ulcer healing, amputation, ulcer recurrence, cardiac or cerebrovascular events and death. The associations between eGFR and the outcomes were analysed by Cox proportional-hazards models. RESULTS: Compared to patients with normal eGFR, patients with moderately reduced eGFR had higher risk of healing failure (hazard ratio (HR) = 2.08, 95% confidence interval (CI): 1.13-3.82), cardiac events (HR = 5.25, 95% CI: 2.17-12.89) and death (HR = 3.54, 95% CI: 1.36-9.20). Severely reduced eGFR was associated with higher incidence of healing failure (HR = 2.84, 95% CI: 1.25-6.49) and death (HR = 4.45, 95% CI: 1.23-16.07). The impact of eGFR on ulcer recurrence and cerebrovascular events was not observed in all groups. CONCLUSIONS: Moderately and severely reduced eGFR in patients with DFU were independent predictors for poor prognoses of both the limbs and the patients.

[Clinical analysis of 23 patients with ossifying fibroma of paranasal sinuses].

OBJECTIVE: To investigate the clinical features and treatment options of ossifying fibroma of paranasal sinuses. METHOD: A retrospective evaluation of twenty-three patients with ossifying fibroma of paranasal sinuses was presented. The choice of surgical operations on ossifying fibroma of paranasal sinuses was mainly decided by the location and area of ossifying fibroma. Radical operations were performed in twenty-one patients, ten of them through a lateral rhinotomy approach, eight through nasal endoscopic approach, four through Caldwell-Luc approach, one through coronal approach. RESULT: Two patients were performed partial resection by nasal endoscopic surgery. Diagnoses of all cases were confirmed by pathology. All patients outcomes were successful, no serious complication from the surgical technique occurred. Twenty cases were followed-up for six months to nineteen years. Two patients recurred. CONCLUSION: Earlier diagnosis, CT scan, proper surgery, and radical resection are the keys to the treatment of ossifying fibroma of paranasal sinuses.

Heart failure in hospitalized patients with diabetic foot ulcers: clinical characteristics and their relationship with prognosis.

BACKGROUND: In the present study we: (i) evaluated the incidence of heart failure (HF) in patients with diabetic foot ulcer (DFU); and (ii) investigated the relationship between the clinical characteristics in these patients and prognosis. METHODS: The clinical characteristics of 330 consecutive Chinese patients (137 men, 193 women) hospitalized for DFU were collected and assessed to determine the effects of HF on DFU. All patients were followed for 3 months and rates of healing, the development of new ulcers, amputations, and mortality were calculated at the end of the follow-up period. RESULTS: Heart failure was present in 64.3% of patients with DFU, with the prevalence of HF increasing with Wagner grade from Wagner 1 through to Wagner 5 (42.4%, 59.1%, 64.7%, 73.3%, and 87.0%, respectively), higher than the 33.6% prevalence in diabetic patients without DFU (Wagner 0). The presence of HF conferred a greater increased relative risk of a worse prognosis. The 3-month healing rates of DFU in patients with and without HF were 60.3% and 75.7%, respectively. Recurrence (13.2% vs 7.5%) and amputations (28.6% vs 20.0%) were more frequent in patients with than without HF (P < 0.05). All-cause mortality was recorded for 14 of 126 patients with HF compared with three of 70 patients without HF (11.1% vs 4.3%, respectively; P < 0.05). CONCLUSIONS: The prevalence of HF is high in Chinese inpatients with DFU, with the presence of HF indicating a worse prognosis for these patients.

Hormones other than aldosterone may contribute to hypertension in 3 different subtypes of primary aldosteronism.

Blood pressure (BP) level is similar in patients with 3 subtypes of primary aldosteronism (PA), even though aldosterone levels may vary. Glucocorticoids and adrenomedullary hormones may be influenced and may contribute to hypertension in PA. The authors' objective was to investigate the influence of PA on adrenal gland secretion and the roles of these hormones in hypertension. Patients diagnosed with PA (229 cases) were enrolled and classified into 3 subgroups: aldosterone-producing adenoma (APA), unilateral nodular adrenal hyperplasia (UNAH), and idiopathic hyperaldosteronism (IHA). Patients with essential hypertension served as the control group (100 cases). Concentration of the above hormones was measured and compared between groups. Level of plasma adrenocorticotrophic hormone (ACTH) in patients with APA was significantly lower than that in patients with IHA (P<.001) and UNAH (P<0.5). The 24-hour urinary free cortisol and adrenomedullary hormone levels were highest in patients with IHA, lower in patients with APA, and lowest in patients with UNAH. Systolic BP level was positively correlated with 8 am plasma cortisol level (r=0.142, P=.039) and plasma ACTH level (r=0.383, P=.016). Cortisol and adrenomedullary hormones were different between PA subtypes and they might involve regulation of BP in those patients.

Nutritional status deteriorates as the severity of diabetic foot ulcers increases and independently associates with prognosis.

The prognosis for diabetic foot ulcers (DFUs) remains poor. Nutritional status has not been identified as one of the factors affecting the outcome of DFUs. Therefore, indicators correlated with nutritional status and outcome were analyzed to investigate their relationship. A total of 192 hospitalized patients with Wagner grade 1-5 ulcers and 60 patients with Wagner grade 0 ulcers (all had type 2 diabetes) were assessed by the following: subjective global assessment (SGA), anthropometric measurements, biochemical indicators and physical examinations to evaluate nutritional status, severity of infection and complications. Patient outcome was recorded as healing of the ulcer and the patients were followed up for 6 months or until the wound was healed. The percentage of malnutrition was 62.0% in the DFU patients. The SGA was closely correlated with infection (r=0.64), outcome (r=0.37) and BMI (r=-0.36), all P<0.001. The risk of poor outcome increased with malnutrition [odds ratio (OR), 10.6, P<0.001]. The nutritional status of the DFU patients was independently correlated with the severity of infection and outcome (both P<0.001) and Wagner grades and nutritional status (SGA) were independent risk factors for patient outcome (both P<0.001). Nutritional status deteriorated as the severity of the DFU increased, and malnutrition was a predictor of poor prognosis.

[The combined application of dissociate skin flap and vacuum sealing drainage on the defect of the large neck neoplasms after surgical procedures].

OBJECTIVE: To evaluate the effect of the combined application of dissociate skin flap and vacuum sealing drainage (VSD) for the repairing for defect after surgical management of huge neck neoplasms. METHOD: Nineteen patients with huge neck malignant tumor involving the skin of the neck were given radical operation, making use of VSD covering the wound surface. After giving 6.65-7.98 mm Hg continuous negative pressure drainage for 72 h, the patients turned to be treated by intermittent negative pressure therapy with 2 min free interval after each treatment period for 5 min. After dismantling the VSD at 7th to 10th day postoperatively, the good wounds covered by granulation tissue were treated by the skin graft operation with dissociate skin flap from thighs; as for the wounds of which the granulation tissue didn't grow well and important cervical tissues was not fully covered by the granulation tissue, VSD was applied again for 1 week, followed by the skin graft operation. RESULT: Nineteen patients have received a total of 23 times of VSD wound treatment, one-stage operation time was significantly shortened. The granulation tissue grew faster on the wound after VSD treatment, and the important cervical tissues such as great vessels could be well covered. The infection and tumor recurrence were observed directly after dismantling the VSD. The skin graft transplantation would be performed after 1-3 weeks. CONCLUSION: The treatment by vacuum sealing drainage combined with skin graft for surgical wounds of huge neck tumor postoperatively has the advantages of simple operation, little injury and promotion of the wound healing, which is an effective way for treatment of neck skin defect by surgical operation for the huge tumor.

Two unusual cases of intractable hyperthyroidism responsive to octreotide: Munchausen syndrome or not?

BACKGROUND: The effective treatment for patients with resistant hyperthyroidism is difficult. METHODS: In this case report with 4-year follow-up data, we present 2 unusual cases of hyperthyroidism that were unresponsive to almost all antithyroid treatments including total thyroidectomy, but both were controlled with octreotide. RESULTS: Cases 1 and 2 were both middle-aged women. They presented thyrotoxicosis with a low serum concentration of TSH and thyroidal radioactive iodine uptake (RAIU). The underlying causes, such as thyroiditis, metastatic thyroid cancer and struma ovarii were explored. Iodine-induced hyperthyroidism, particularly factitious hyperthyroidism was highly suspected, but there was no direct evidence to establish these diagnoses. In spite of good compliance, their thyrotoxicosis could not be controlled with large doses of PTU or MMI. ß-blocker, methylprednisolone, radio-iodine therapy and even thyroidectomy were all attempted and failed. Short-acting octreotide was first administered to case 1 and then to case 2. Thyroid function improved greatly within 3 days in both cases. The doses of octreotide were tapered down to twice a week with consistent efficacy. During the follow-up periods, case 1 required octreotide 0.1mg twice per week and case 2 is on thyroid replacement therapy due to hypothyroidism. The recurrences of hyperthyroidism in both cases were again rapidly controlled with the increased dose of octreotide in case 1 and re-started the usage of octreotide in case 2. CONCLUSIONS: The etiology of thyrotoxicosis in these 2 cases is not clear. In the absence of struma ovarii or wide-spread follicular thyroid cancer, factitious hyperthyroidism due to Munchausen syndrome should be considered first. The efficacy of the off-label use of octreotide in hyperthyroidism was highly effective (only) in these 2 cases.

[Efficacy and safety of high-dose α-lipoic acid in the treatment of diabetic polyneuropathy].

OBJECTIVE: To evaluate the efficacy and safety of high-dose α-lipoic acid in the treatment of diabetic polyneuropathy with regards to sensory symptoms and nerve conduction velocity. METHODS: A total of 236 diabetics with symptomatic polyneuropathy were enrolled into this 5-center, randomized, double-blind and placebo-controlled study of α-lipoic acid 1800 mg daily (n = 117) or matching placebo (n = 119) for 12 weeks. The primary outcome was total symptom score (TSS). Secondary end points included nerve conduction velocity, individual symptom score, HbA1c and safety parameters. The above parameters were reviewed and recorded at zero point and after treatment for 2, 4, 8, 12 weeks separately. RESULTS: 73.27% patients with symptomatic polyneuropathy improved after treatment with α-lipoic acid for 12 weeks versus 18.27% with placebo. TSS declined by 2.6 ± 2.3 with α-lipoic acid. And it was more than 0.7 ± 1.4 versus placebo (P < 0.05). TSS decreased quickly after treatment with α-lipoic acid for 2 weeks (P < 0.05). And it was better than placebo. Individual symptom scores of pain, extremity numbness, burning sensation or resting abnormal sensations were significantly diminished as compared to those before treatment and placebo group (all P < 0.05). Nerve conduction velocity had no change. HbA1c further decreased at the end of trial after α-lipoic acid treatment (P < 0.05). The incidence rates of adverse effects were 25.4% vs 11.8% in the treatment and control groups. The major manifestation was burning sensation from throat to stomach (12.7%). CONCLUSION: Oral treatment with high-dose α-lipoic acid for 12 weeks may improve symptoms in patients with diabetic polyneuropathy. Dose of 600 mg thrice daily for 2 weeks has marked effects with a reasonable safety.

A patient with pseudohypoaldosteronism type II caused by a novel mutation in WNK4 gene.

Pseudohypoaldosteronism Type II (PHAII) is a very rare disorder characterized by hyperkalemia, hypertension, and slight hyper-chloremic metabolic acidosis. The index patient showed typical features of PHAII, including elevated blood pressure (140-150/90-100 mmHg), hyperkalemia in the range of 5.30-5.60 mmol/l (normal range is 3.50-5.10 mmol/l), accompanied by hyperchloremia of 109.5-112.0 mmol/l (normal 95.0-108.0 mmol/l) and acidosis with bicarbonate levels of 19.5-20.1 mmol/l (normal 22.0-27.0), GFR was 98.95 ml/min (normal > 90). However, these features were absent in his parents. Sequencing analysis found the patient with a WNK4 gene mutation, 1682 C > T in Exon 7, which resulted a missense mutation at codon 561 (P561L). The variation in codon 561 was not found in his parents and 100 unrelated control subjects. The identified WNK4 mutation which has not been described previously is the probable cause of PHAII.

RET proto-oncogene mutations are restricted to codons 634 and 918 in mainland Chinese families with MEN2A and MEN2B.

OBJECTIVE: Multiple endocrine neoplasia type 2 is caused by autosomal dominant gain-of-function mutations in the RET proto-oncogene, which includes multiple endocrine neoplasia type 2A (MEN2A), type 2B (MEN 2B), and familial medullary thyroid carcinoma (FMTC). In this paper we present the phenotype-genotype correlation of 20 unrelated Chinese families with 15 cases of MEN2A and five cases of MEN2B. DESIGN: Cross-sectional study. PATIENTS: A total of 147 members from the 20 families were included. Among them, 119 family members were from MEN2A pedigrees (including 15 MEN2A probands) and 28 members from MEN2B pedigrees (including five MEN2B probands). MEASUREMENTS: Genomic DNA was isolated from peripheral blood leucocytes and was amplified using polymerase chain reaction (PCR). DNA analysis for RET mutations in exons 8, 10, 11, 13, 14, 15 and 16 was performed with specific primers. RESULTS: Thirty-seven MEN2A and five MEN2B patients were identified as having RET mutations. The incidence of medullary thyroid carcinoma (MTC), pheochromocytoma (PCC) and hyperparathyroidism (HPT) in the 37 MEN2A patients was 91.9, 56.8 and 10.8%, respectively; the onset of MTC in MEN2A patients was earlier than that of PCC and HPT. Five germline mutations, all located at codon 634 of exon11 in the RET proto-oncogene, were detected in all of the 37 MEN2A patients. The highest frequency of the five germline mutations was C634Y (46.7%), followed by C634R (26.7%), C634W (13.3%), C634F (6.7%) and C634S (6.7%). No statistical significance was found between the incidence of PCC and different genotypes of codon 634 in MEN2A patients, whereas the incidence of HPT was closely associated with C634R and C634Y. The gene mutation (M918T) at exon16 of the RET proto-oncogene was present in five MEN2B probands. CONCLUSIONS: RET proto-oncogene mutations were restricted to codon 634 and 918 in Chinese families with MEN2A and MEN2B. In general the genetic characteristics of these patients with MEN2A and MEN2B reflect the general pattern around the world and it remains to be determined with larger studies in China whether Chinese patients have a different genetic pattern of mutations.

[Risk factors for cardiovascular autonomic neuropathy and their prognostic implications in type 2 diabetes mellitus].

OBJECTIVE: Risk factors for diabetic cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes were analyzed to establish a regression model for evaluating the diagnosis of CAN. METHODS: 325 patients with type 2 diabetes were divided into four groups according to the results of four standard function tests. Every patient was required to offer detailed disease history and accept physical examination, serum and urine tests and examinations including ECG, nerve conduction velocity, retinoscope and Doppler of carotid and lower limb arteries. RESULTS: 64.0% of the patients had abnormal autonomic function and 30.2% definite CAN. There was significant difference among groups about age, average glycosylated forms of hemoglobin (HbA1c), systolic blood pressure, corrected 24 h albumin excretion and heart rate at rest (P < 0.001). The incidence of diabetic complications and accompanying diseases increased with deterioration of CAN (P < 0.05). The regression model showed that age, average HbA1c, hypertension, peripheral neuropathy, retinopathy, tachycardia at rest and duration of peripheral neuropathy were significant related factors for CAN. With these factors, a mathematic formula was established which could be used for evaluating the diagnosis of CAN. CONCLUSION: Except for age and hypertension, risk factors were all induced by hyperglycemia. It is suggested that control of hyperglycemia is of primary importance in preventing diabetic complications.