[Clinical diagnosis of group A streptococcal pharyngitis and progress in the application of scoring systems]. / A族链球菌咽炎的临床诊断及评分制的应用进展.

Pharyngitis can be caused by various pathogens, including viruses and bacteria. Group A streptococcus (GAS) is the most common bacterial cause of pharyngitis. However, distinguishing GAS pharyngitis from other types of upper respiratory tract infections is challenging in clinical settings. This often leads to empirical treatments and, consequently, the overuse of antimicrobial drugs. With the advancement of antimicrobial drug management and healthcare payment reform initiatives in China, reducing unnecessary testing and prescriptions of antimicrobial drugs is imperative. To promote standardized diagnosis and treatment of GAS pharyngitis, this article reviews various international guidelines on the clinical diagnosis and differential diagnosis of GAS pharyngitis, particularly focusing on clinical scoring systems guiding laboratory testing and antimicrobial treatment decisions for GAS pharyngitis and their application recommendations, providing a reference for domestic researchers and clinical practitioners.

Multi-omics reveals that alkaline mineral water improves the respiratory health and growth performance of transported calves.

BACKGROUND: Long-distance transportation, a frequent practice in the cattle industry, stresses calves and results in morbidity, mortality, and growth suppression, leading to welfare concerns and economic losses. Alkaline mineral water (AMW) is an electrolyte additive containing multiple mineral elements and shows stress-mitigating effects on humans and bovines. RESULTS: Here, we monitored the respiratory health status and growth performance of 60 Simmental calves subjected to 30 hours of road transportation using a clinical scoring system. Within the three days of commingling before the transportation and 30 days after the transportation, calves in the AMW group (n = 30) were supplied with AMW, while calves in the Control group (n = 29) were not. On three specific days, namely the day before transportation (day -3), the 30th day (day 30), and the 60th day (day 60) after transportation, sets of venous blood, serum, and nasopharyngeal swab samples were collected from 20 calves (10 from each group) for routine blood testing, whole blood transcriptomic sequencing, serology detection, serum untargeted metabolic sequencing, and 16S rRNA gene sequencing. The field data showed that calves in the AMW group displayed lower rectal temperatures (38.967 ℃ vs. 39.022 ℃; p = 0.004), respiratory scores (0.079 vs. 0.144; p < 0.001), appetite scores (0.024 vs. 0.055; p < 0.001), ocular and ear scores (0.185 vs. 0.338; p < 0.001), nasal discharge scores (0.143 vs. 0.241; p < 0.001), and higher body weight gains (30.870 kg vs. 7.552 kg; p < 0.001). The outcomes of laboratory and high throughput sequencing data revealed that the calves in the AMW group demonstrated higher cellular and humoral immunities, antioxidant capacities, lower inflammatory levels, and intestinal absorption and lipogenesis on days -3 and 60. The nasopharynx 16S rRNA gene microbiome analysis revealed the different composition and structure of the nasopharyngeal microflora in the two groups of calves on day 30. Joint analysis of multi-omics revealed that on days -3 and 30, bile secretion was a shared pathway enriched by differentially expressed genes and metabolites, and there were strong correlations between the differentially expressed metabolites and the main genera in the nasopharynx. CONCLUSIONS: These results suggest that AMW supplementation enhances peripheral immunity, nutrition absorption, and metabolic processes, subsequently affecting the nasopharyngeal microbiota and improving the respiratory health and growth performance of transported calves. This investigation provided a practical approach to mitigate transportation stress and explored its underlying mechanisms, which are beneficial for the development of the livestock industry. Video Abstract.

Clinical Scoring of Disease Activity in Animal Models.

Disease severity in murine arthritis models, such as collagen-induced arthritis (CIA), is commonly assessed by clinical scoring of paw swelling and histological examination of joints. Clinical scoring using a qualitative scoring system of paw inflammation (paw thickness, width, or volume) over time is the standard method used for subjective quantification of arthritis activity. To evaluate paw swelling status, a quantitative method using three-dimensional T2-weighted flash sequence magnetic resonance imaging (MRI) is introduced. The efficacy of a therapeutic approach can be semiologically quantified using a clinical scoring system and an index of paw inflammation in CIA mice.

Quantitative DNA Methylation Analysis and Epigenotype-Phenotype Correlations in Taiwanese Patients with Silver-Russell Syndrome.

Background: Silver-Russell syndrome (SRS; OMIM #180860) is a clinically and genetically heterogeneous imprinting disorder characterized by prenatal and postnatal growth failure. The aim of this study was to identify the epigenotype-phenotype correlations in these patients using quantitative DNA methylation analysis. Methods: One hundred and eighty-three subjects clinically suspected of having SRS were referred for diagnostic testing by the methylation profiling of H19-associated imprinting center (IC) 1 and imprinted PEG1/MEST regions using methylation-specific high-resolution melting analysis and methylation quantification with the MassARRAY assay. Correlations between quantitative DNA methylation status and clinical manifestations of the subjects according to the Netchine-Harbison (N-H) clinical scoring system for SRS were analyzed. Results: Among the 183 subjects, 90 had a clinical diagnosis of SRS [N-H score ≥ 4 (maximum = 6)] and 93 had an SRS score < 4. Molecular lesions were detected in 41% (37/90) of the subjects with a clinical diagnosis of SRS, compared with 3% (3/93) of those with an N-H score < 4. The IC1 methylation level was negatively correlated with the N-H score. The molecular diagnosis rate was positively correlated with the N-H score. Thirty-one subjects had IC1 hypomethylation (IC1 methylation level <35% by the MassARRAY assay), seven had maternal uniparental disomy 7, and two had pathogenic copy number variants. Among the 90 subjects with an N-H score ≥ 4, the IC1 methylation level was significantly different between those with or without some clinical SRS features, including birth length ≤ 10th centile, relative macrocephaly at birth, normal cognitive development, body asymmetry, clinodactyly of the fifth finger, and genital abnormalities. Conclusions: This study confirmed the suitability of the N-H clinical scoring system as clinical diagnostic criteria for SRS. Quantitative DNA methylation analysis using the MassARRAY assay can improve the detection of epigenotype-phenotype correlations, further promoting better genetic counseling and multidisciplinary management for these patients.

Prevalence of respiratory disease in Irish preweaned dairy calves using hierarchical Bayesian latent class analysis.

Introduction: Bovine respiratory disease (BRD) has a significant impact on the health and welfare of dairy calves. It can result in increased antimicrobial usage, decreased growth rate and reduced future productivity. There is no gold standard antemortem diagnostic test for BRD in calves and no estimates of the prevalence of respiratory disease in seasonal calving dairy herds. Methods: To estimate BRD prevalence in seasonal calving dairy herds in Ireland, 40 dairy farms were recruited and each farm was visited once during one of two calving seasons (spring 2020 & spring 2021). At that visit the prevalence of BRD in 20 calves between 4 and 6 weeks of age was determined using thoracic ultrasound score (≥3) and the Wisconsin respiratory scoring system (≥5). Hierarchical Bayesian latent class analysis was used to estimate the calf-level true prevalence of BRD, and the within-herd prevalence distribution, accounting for the imperfect nature of both diagnostic tests. Results: In total, 787 calves were examined, of which 58 (7.4%) had BRD as defined by a Wisconsin respiratory score ≥5 only, 37 (4.7%) had BRD as defined by a thoracic ultrasound score of ≥3 only and 14 (1.8%) calves had BRD based on both thoracic ultrasound and clinical scoring. The primary model assumed both tests were independent and used informed priors for test characteristics. Using this model the true prevalence of BRD was estimated as 4%, 95% Bayesian credible interval (BCI) (1%, 8%). This prevalence estimate is lower or similar to those found in other dairy production systems. Median within herd prevalence varied from 0 to 22%. The prevalence estimate was not sensitive to whether the model was constructed with the tests considered conditionally dependent or independent. When the case definition for thoracic ultrasound was changed to a score ≥2, the prevalence estimate increased to 15% (95% BCI: 6%, 27%). Discussion: The prevalence of calf respiratory disease, however defined, was low, but highly variable, in these seasonal calving dairy herds.

A Case Report of Culture-Negative Necrotizing Fasciitis With Low Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) Score: A Diagnostic Dilemma.

The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score is a diagnostic tool used to help clinicians identify necrotizing fasciitis (NF) in its early stages. This tool uses six laboratory values including the patient's white blood cell count, C-reactive protein level, serum sodium level, creatinine level, and hemoglobin level to help with risk stratification. Each of these laboratory values is assigned a point value and the total score is used to determine the likelihood that a patient has NF, with a score of 6 or higher considered to be strongly indicative. The LRINEC score has gained popularity in recent years, having been included in guidelines and society recommendations for the management of NF. However, some studies have challenged the validity of the LRINEC score. Prompt and accurate diagnosis of NF is imperative given the associated mortality rate, which can be as high as 30%-40%, especially if the diagnosis is delayed. We present a case of a patient with a delayed diagnosis of NF that was initially missed in the early stages in the setting of a low LRINEC, however, growing clinical suspicion eventually led to an accurate diagnosis and management.

Surgical Candidacy for Management of Laryngomalacia: A Proposed Scoring System.

Introduction: Identifying surgical candidacy for the management of laryngomalacia is a challenge. Objective: To develop a simple scoring system for surgical candidacy in laryngomalacia. Methods: Eighteen years retrospective observational study of children with laryngomalacia (LM) clinically categorized into mild, moderate and severe LM and were analyzed for surgical candidacy. Results: There were 113 children (age ranging from 5 days to 14 months), 44% being mild, 30% moderate and 26% severe LM. None in mild, 32% in moderate, and all in severe LM had surgical intervention. Presence of stridor on feeding or crying and isolated type 1 or type 2 LM on laryngoscopy were significant indicators for conservative treatment (p-< 0.0001). Moderate failure to thrive, retraction at rest/sleep, with low oxygen saturation while feeding/at rest were significantly higher in both moderate and severe groups with laryngoscopic evidence of combined type 1 and 2 in moderate LM (p < 00,001). Aspiration pneumonia, hospitalization, pectus and mean pulmonary arterial pressure of more than 25 mmHg with laryngoscopic findings of all three combined types were significantly higher in severe LM (p < 0.0001).A simple scoring system was then developed and it revealed that a score of 10 or more required surgical intervention. Conclusion and clinical significance: A clinical scoring system is being reported for the first time in medical literature to identify 'the difficult to treat' subset within moderate laryngomalacia category simplifying decision making in its management for otolaryngologists and pediatricians as well as a referral criterion for pediatric otolaryngologists' services.

Clinical characteristics of dry eye in patients with type 2 diabetic peripheral neuropathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical features of dry eye in patients with type 2 diabetes mellitus complicated with peripheral neuropathy.METHOD: Prospective cohort study. A total of 192 patients with type 2 diabetes were enrolled in the Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from July 2021 to March 2022. The right eyes of all patients were selected as the observation eye, among which 122 patients were diagnosed with diabetic peripheral neuropathy(DPN)and 70 patients were diagnosed with non-diabetic peripheral neuropathy(NDPN). The score of ocular surface disease index(OSDI), tear meniscus height, tear meniscus width, corneal epithelial thickness, corneal endothelial cell density, tear secretion test(Schirmer Ⅰ test, SⅠt), corneal sensitivity, meibomian gland function status score, tear film breakup time(BUT), corneal fluorescein sodium staining score and Toronto clinical scoring system(TCSS)score were compared between two groups. The correlation between OSDI score and TCSS score in type 2 diabetes patients was analyzed as well.RESULTS: The morbidity of dry eye in the DPN group(55 eyes, 45.1%)was significantly higher than that of NDPN group(20 eyes, 28.6%; χ2=5.094, P=0.024), BUT and corneal sensitivity score of DPN were lower than NDPN group(P&#x003C;0.001), meanwhile, corneal staining score and meibomian gland function score were higher than NDPN group(P&#x003C;0.001). OSDI scores of all subjects were negatively correlated with TCSS scores(rs=-0.233, P=0.002), and OSDI scores of DPN group were negatively correlated with TCSS scores(rs=-0.511, P&#x003C;0.001), but there was no significant correlation between the two scores of NDPN patients(rs=0.007, P=0.957).CONCLUSIONS: DPN patients are more likely to develop dry eye than NDPN patients. OSDI score is not an accurate evaluation index for type 2 diabetes patients, especially for DPN patients.

Medical imaging for pancreatic diseases: Prediction of severe acute pancreatitis complicated with acute respiratory distress syndrome.

In this editorial we comment on the article published in the recent issue of the World Journal of Gastroenterology [2022; 28 (19): 2123-2136]. We pay attention to how to construct a simpler and more reliable new clinical predictive model to early identify patients at high risk of acute respiratory distress syndrome (ARDS) associated with severe acute pancreatitis (SAP), and to early predict the severity of organ failure from chest computed tomography (CT) findings in SAP patients. As we all know, SAP has a sudden onset, is a rapidly changing condition, and can be complicated with ARDS and even multiple organ dysfunction syndrome, and its mortality rate has remained high. At present, there are many clinical scoring systems for AP, including the bedside index for severity in AP, acute physiology and chronic health evaluation II, systemic inflammatory response syndrome, Japanese severe score, quick sepsis-related organ failure assessment, etc. However, some of these scoring systems are complex and require multiple and difficult clinical parameters for risk stratification. Although the aforementioned biomarkers are readily available, their ability to predict ARDS varies. Accor-dingly, it is extremely necessary to establish a simple and valuable novel model to predict the development of ARDS in AP. In addition, the extra-pancreatic manifestations of AP patients often involve the chest, among which pleural effusion and pulmonary consolidation are the more common complications. Therefore, by measuring the semi-quantitative indexes of chest CT in AP patients, such as the amount of pleural effusion and the number of lobes involved as pulmonary consolidation, it has important reference value for the early diagnosis of SAP complicated with ARDS and is expected to provide a basis for the early treatment of ARDS.

Comparing Clinical and Genetic Characteristics of De Novo and Inherited COL1A1/COL1A2 Variants in a Large Chinese Cohort of Osteogenesis Imperfecta.

Purpose: Nearly 85%-90% of osteogenesis imperfecta (OI) cases are caused by autosome dominant mutations of COL1A1 and COL1A2 genes, of which de novo mutations cover a large proportion, whereas their characteristics remain to be elucidated. This study aims to compare the differences in clinical and genetic characteristics of de novo and inherited COL1A1/COL1A2 mutations of OI, assess the average paternal and maternal age at conception in de novo mutations, and research the rate of nonpenetrance in inherited mutations. Materials and Methods: A retrospective comparison between de novo and inherited mutations was performed among 135 OI probands with COL1A1/COL1A2 mutations. Mutational analyses of all probands and their family members were completed by Sanger sequencing. A new clinical scoring system was developed to assess the clinical severity of OI quantitatively. Results: A total of 51 probands (37.78%) with de novo mutations and 84 probands (62.22%) with inherited mutations were grouped by the results of the parental gene verification. The proportion of clinical type III (P<0.001) and clinical scores (P<0.001) were significantly higher in de novo mutations. Missense mutations covered a slightly higher proportion of de novo COL1A1 mutations (46.34%) compared with inherited COL1A1 mutations (33.33%), however, lacking a significant difference (P=0.1923). The mean BMD Z/T-score at the lumbar spine in de novo mutations was -2.3 ± 1.5, lower than inherited mutations (-1.7 ± 1.8), but lacking statistical significance (P=0.0742). There was no significant difference between the two groups in OI-related phenotypes (like fracture frequency, blue sclera, and hearing loss) and biochemical indexes. In de novo mutations, the average paternal and maternal age at conception was 29.2 (P<0.05) and 26.8 (P<0.0001), respectively, which were significantly younger than the average gestational age of the population. Additionally, 98.04% of pedigrees (50/51) with de novo mutations were spontaneous conception. The rate of nonpenetrance of parents with pathogenic variants in the inherited mutation group was 25.64% (20/78). Conclusions: Our data revealed that the proportion of clinical type III and clinical scores were significantly higher in de novo mutations than in inherited mutations, demonstrating that de novo mutations are more damaging because they have not undergone purifying selection.

Impaired Vascular Endothelial Function is Associated with Peripheral Neuropathy in Patients with Type 2 Diabetes.

Purpose: It is believed that vascular endothelial dysfunction is involved in the occurrence of cardiovascular disease (CVD), and diabetic peripheral neuropathy (DPN) is associated with flow-mediated dilation (FMD), however, the correlation is still unclear. Aims of the present study is to explore the relationship between DPN parameters and FMD, providing a new approach for the prevention of CVD. Patients and Methods: A total of 272 patients with T2DM from the Department of Endocrinology of The First Hospital of Lanzhou University according to the grading criteria were selected. FMD was measured by a new vascular ultrasound system and patients were divided into FMD>7%, 4%≤FMD≤7%, and FMD<4% groups. The Toronto Clinical Scoring System (TCSS) was used to assess the severity of DPN. The nerve conduction studies (NCS) assessed large fibre neuropathy by nerve conduction velocity (CV), compound muscle action potential (CMAP) amplitude (Amp), and distal motor latency (DML). SPSS 25.0 was used for statistical analysis. Results: TCSS evaluation revealed that the percentage of patients with severe nerve injury was significantly higher in FMD<4% (70%) compared to FMD>7% (2%). Among the TCSS indicators of all subjects, the proportion of temperature disturbance was the most (73%), and joint position disturbance was the least (0). TCSS scores were negatively correlated with FMD (r=-0.756, p<0.001). More interesting, in FMD<4% group, CV and Amp were positively correlated with FMD, while DML was negatively correlated (p<0.05). Linear regression analysis model showed that different systolic blood pressure (SBP), triglyceride (TG), TCSS and CV had statistically different effects on FMD. Conclusion: High TCSS score and decreased CV of common peroneal and tibial nerves are risk factors of FMD injury, which provide potential value for timely prevention and treatment of cardiovascular diseases.

Effect of Severity of Liver Cirrhosis on Surgical Outcomes of Hepatocellular Carcinoma After Liver Resection and Microwave Coagulation.

BACKGROUND: Liver resection (LR) and percutaneous microwave coagulation therapy (PMCT) are both considered as radical treatments for small hepatocellular carcinoma (HCC). However, it is still unclear whether to select LR or PMCT in HCC patients with different degrees of liver cirrhosis. The purpose of this study was to compare the efficacy of LR and PMCT in the treatment of solitary and small HCC accompanied with different degrees of liver cirrhosis. METHODS: In this study, 230 patients with solitary HCC lesions ≤ 3 cm and Child-Pugh A liver function were retrospectively reviewed. Among these patients, 122 patients underwent LR, and 108 received PMCT. The short- and long-term outcomes were compared between these two procedures. Severity of liver cirrhosis was evaluated by using clinical scoring system (CSS) as previously published. Subgroup analysis based on CSS was performed to evaluate the effect of severity of liver cirrhosis on surgical outcomes after LR and PMCT. RESULTS: There was no mortality within 90 days in both groups. Major complications were significantly more frequent in the LR group than in the PMCT group (18.8% vs. 4.6%, p<0.001). However, LR provided better surgical outcomes than PMCT. The 5-year overall survival (OS) rates for the LR and PMCT groups were 65.2% and 42%, respectively (p=0.006), and the corresponding disease-free survival (DFS) rates were 51.7% and 31.5%, respectively (p=0.004). Nevertheless, subgroup analysis showed that PMCT provided long-term outcomes that were similar to LR and lower surgical complications in HCC patients with CSS score≥4. CONCLUSIONS: LR may provide better OS and DFS rates than PMCT for patients with solitary HCC lesions ≤ 3 cm and Child-Pugh A liver function irrespective of liver cirrhosis. PMCT should be viewed as the optimal treatment for solitary and small HCC with severe cirrhosis.

SIMPLE: A Novel Scoring System for Predicting Hemodynamically Significant Patent Ductus Arteriosus Without Echocardiographic Evaluation in Extremely Low Birth Weight Infants.

Aim: To develop a novel clinical scoring system for predicting hemodynamically significant patent ductus arteriosus (hsPDA) in extremely low birth weight (ELBW) infants. Methods: A prospective observational study was conducted among ELBW infants born in the study center during a 6-month period. Fourteen items were selected on a literature review basis and weighed by severity on an arbitrary 1-4 scale, the sum of which represented the Scoring preterm Infants for PDA cLinically without Echocardiographic evaluation (SIMPLE) score. The SIMPLE scores were compared at several time points during the first 3 days of life between two groups of patients: those with an hsPDA at echocardiography and those without. Results: A total of 48 ELBW infants were enrolled, of which 30 infants developed hsPDA. The SIMPLE scores of the infants with hsPDA were significantly greater than those of the infants who did not develop hsPDA. Cut-off SIMPLE scores that were significantly associated with detection of symptomatic hsPDA at each evaluation time point were identified. Conclusions: SIMPLE is the first scoring system that depends on the risk factors and clinical findings of ELBW infants for early prediction of hsPDA. It is simple, objective and easy to perform, and it does not require any additional tests and/or echocardiographic evaluation. We suggest that SIMPLE can be used as a screening tool for determining the need for echocardiographic evaluation in ELBW infants in order to minimize the number of unnecessary pediatric cardiology consultations.

Clinical Application of Sequential Epigenetic Analysis for Diagnosis of Silver-Russell Syndrome.

BACKGROUND: Silver-Russell syndrome (SRS) is a pre- or post-natal growth retardation disorder caused by (epi)genetic alterations. We evaluated the molecular basis and clinical value of sequential epigenetic analysis in pediatric patients with SRS. METHODS: Twenty-eight patients who met≥3 Netchine-Harbison clinical scoring system (NH-CSS) criteria for SRS were enrolled;26 (92.9%) were born small for gestational age, and 25 (89.3%) showed postnatal growth failure. Relative macrocephaly, body asymmetry, and feeding difficulty were noted in 18 (64.3%), 13 (46.4%), and 9 (32.1%) patients, respectively. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) on chromosome 11p15 was performed as the first diagnostic step. Subsequently, bisulfite pyrosequencing (BP) for imprinting center 1 and 2 (IC1 and IC2) at chromosome 11p15, MEST on chromosome 7q32.2, and MEG3 on chromosome 14q32.2 was performed. RESULTS: . Seventeen (60.7%) patients exhibited methylation defects, including loss of IC1 methylation (N=14; 11 detected by MS-MLPA and three detected by BP) and maternal uniparental disomy 7 (N=3). The diagnostic yield was comparable between patients who met three or four of the NH-CSS criteria (53.8% vs 50.0%). Patients with methylation defects responded better to growth hormone treatment. CONCLUSIONS: NH-CSS is a powerful tool for SRS screening. However, in practice, genetic analysis should be considered even in patients with a low NH-CSS score. BP analysis detected additional methylation defects that were missed by MS-MLPA and might be considered as a first-line diagnostic tool for SRS.

Effect of resistance exercise on peripheral neuropathy in Type 2 diabetes mellitus. / 抗阻力运动对2åž‹ç³–å°¿ç— å‘¨å›´ç¥žç»ç— å˜çš„å½±å“.

OBJECTIVES: To explore the improvement of neurological symptoms in patients with Type 2 diabetic peripheral neuropathy via resistance exercise. METHODS: A total of 100 patients with Type 2 diabetic peripheral neuropathy were selected as the research objects, and they were randomly divided into an observation group who performed resistance exercise (n=50) and a control group who did not performed resistance exercise (n=50). Resistance exercise was performed on the bioDensity™ resistance exercise instrument. The study graded the severity of diabetic peripheral neuropathy by the Toronto clinical scoring system (TCSS), and the improvement of diabetic peripheral neuropathy (DPN) was evaluated by the decline of the TCSS score. The observation group was treated with resistance exercise for 6 months. The changes of body mass index (BMI), waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose (FBG), fasting insulin (FINS), glycosylated hemoglobin (HbA1C), total cholesterol (TC), glycerin trilaurate (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), and TCSS score were compared between baseline and 3, 6 months of exercise. At the same time, the differences in sensory test scores, nerve reflex scores, and neurological symptom scores were compared between the baseline, 3 and 6 months, in the observation group. Except for resistance exercise, the other treatments in the control group were the same as those in the observation group. RESULTS: Compared with the control group, there was statistically difference in the TCSS scores in the observation group at 3 months (P<0.05); there were also statistically difference in the HbA1C and TCSS scores in the observation group at 6 months (both P<0.05). The changes of TCSS scores, FBG, HbA1C in the observation group at 3 months and 6 months were significantly lower than those in the baseline, with significant differences (all P<0.05); but there were no significant differences in BMI, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure and TC, TG, LDL, HDL (all P>0.05). In the TCSS scores, the neurosymptom score, sensory test score were all reduced compared with the baseline, with significant differences (both P<0.05); but there was no significant difference in the neuroreflex score (P>0.05). In the control group, the TG and TC at 3 and 6 months were decreased compared with the baseline, and there was significant difference (both P<0.05), while there was no significant difference in the other indicators (all P>0.05). CONCLUSIONS: After the intervention of resistance exercise, the blood glucose and DPN can be improved in a certain extent, and which can be popularized in Type 2 diabetes patients.

The Clinical Kinase Index: A Method to Prioritize Understudied Kinases as Drug Targets for the Treatment of Cancer.

The approval of the first kinase inhibitor, Gleevec, ushered in a paradigm shift for oncological treatment-the use of genomic data for targeted, efficacious therapies. Since then, over 48 additional small-molecule kinase inhibitors have been approved, solidifying the case for kinases as a highly druggable and attractive target class. Despite the role deregulated kinase activity plays in cancer, only 8% of the kinome has been effectively "drugged." Moreover, 24% of the 634 human kinases are understudied. We have developed a comprehensive scoring system that utilizes differential gene expression, pathological parameters, overall survival, and mutational hotspot analysis to rank and prioritize clinically relevant kinases across 17 solid tumor cancers from The Cancer Genome Atlas. We have developed the clinical kinase index (CKI) app (http://cki.ccs.miami.edu) to facilitate interactive analysis of all kinases in each cancer. Collectively, we report that understudied kinases have potential clinical value as biomarkers or drug targets that warrant further study.

12q14.3 microdeletion involving HMGA2 gene cause a Silver-Russell syndrome-like phenotype: a case report and review of the literature.

BACKGROUND: Silver-Russell Syndrome (SRS) is a genetic disorder characterized by intrauterine and postnatal growth restriction and normal head circumference with consequent relative macrocephaly. Addictional findings are protruding forehead in early life, body asymmetry (of upper and lower limbs) and substantial feeding difficulties. Although several genetic mechanisms that cause the syndrome are known, more than 40% of patients with a SRS-like phenotype remain without an etiological diagnosis. In the last few years, different clinical reports have suggested that mutations or deletions of the HMGA2 gene can be responsible for a SRS-like phenotype in patients with negative results of the common diagnostic tests for this syndrome. CASE PRESENTATION: We present a 3-year-old male patient with clinical diagnosis of Silver-Russell Syndrome (SRS) associated with a de novo heterozygous deletion of the long arm of the chromosome 12 (12q14.3) encompassing the HMGA2 gene. CONCLUSIONS: Our report confirms the etiological role of HMGA2 as a disease gene in the development of a SRS-like phenotype.

Diabetic Peripheral Neuropathy Is Associated With Higher Systolic Blood Pressure in Adults With Type 2 Diabetes With and Without Hypertension in the Chinese Han Population.

OBJECTIVES: Our aim in this study was to investigate the association between diabetic peripheral neuropathy (DPN) and above-normal blood pressure in nonhypertensive adult patients with type 2 diabetes mellitus (T2DM). We also compared achievement of clinical targets for DPN and non-DPN with T2DM. METHODS: A retrospective survey was administered to 3,810 patients with T2DM. Cases were grouped according to the Toronto Clinical Scoring System as follows: non-DPN, mild DPN, moderate DPN and severe DPN. A total of 1,835 patients (hypertensive, 1,247; nonhypertensive, 588) also underwent nerve conduction velocity testing, and then was divided into quartile groups. RESULTS: Irrespective of hypertension, systolic blood pressure (SBP) and glycated hemoglobin levels in the DPN group were higher than those in the non-DPN group (p<0.001). In hypertensive patients, blood pressure goal achievement was lower in the DPN group compared with the non-DPN group (31.1% vs 40.5%, p<0.05). Compared with the nerve conduction velocity Q1 (P75%) groups decreased by 62.2%, 68.2% and 78.0%, respectively. In the nonhypertensive patients, detection of optimal SBP was lower in the DPN group than in the non-DPN group (p<0.05). After adjusting for age, sex and diabetes duration (model 2), a 3-point higher DPN score on the Toronto Clinical Scoring System was associated with an SBP level of 4.2 mmHg higher (95% confidence interval, 0.01 to 0.17; p<0.01) in nonhypertensive patients with diabetes. CONCLUSIONS: DPN is associated with difficulty in hypertension management in T2DM. It is also associated with elevated systolic blood hypertension, even in nonhypertensive patients with diabetes. Elevated SBP in nonhypertensive T2DM may be also worthy of further attention.

Effect of resistance exercise on peripheral neuropathy in Type 2 diabetes mellitus / 中南大学学报(医学版)

OBJECTIVES@#To explore the improvement of neurological symptoms in patients with Type 2 diabetic peripheral neuropathy via resistance exercise.@*METHODS@#A total of 100 patients with Type 2 diabetic peripheral neuropathy were selected as the research objects, and they were randomly divided into an observation group who performed resistance exercise (@*RESULTS@#Compared with the control group, there was statistically difference in the TCSS scores in the observation group at 3 months (@*CONCLUSIONS@#After the intervention of resistance exercise, the blood glucose and DPN can be improved in a certain extent, and which can be popularized in Type 2 diabetes patients.

Molecular Etiology Disclosed by Array CGH in Patients With Silver-Russell Syndrome or Similar Phenotypes.

Introduction: Silver-Russell syndrome (SRS) is an imprinting disorder primarily caused by genetic and epigenetic aberrations on chromosomes 11 and 7. SRS is a rare growth retardation disorder often misdiagnosed due to its heterogeneous and non-specific clinical features. The Netchine-Harbison clinical scoring system (NH-CSS) is the recommended tool for differentiating patients into clinical SRS or unlikely SRS. However, the clinical diagnosis is molecularly confirmed only in about 60% of patients, leaving the remaining substantial proportion of SRS patients with unknown genetic etiology. Materials and Methods: A cohort of 34 Italian patients with SRS or SRS-like features scored according to the NH-CSS and without any SRS-associated (epi)genetic alterations was analyzed by high-resolution array-based comparative genomic hybridization (CGH) in order to identify potentially pathogenic copy number variants (CNVs). Results and Discussion: In seven patients, making up 21% of the initial cohort, five pathogenic and two potentially pathogenic CNVs were found involving distinct genomic regions either previously associated with growth delay conditions (1q24.3-q25.3, 17p13.3, 17q22, and 22q11.2-q11.22) and with SRS spectrum (7p12.1 and 7p15.3-p14.3) or outlined for the first time (19q13.42), providing a better definition of reported and as yet unreported SRS overlapping syndromes. All the variants involve genes with a defined role in growth pathways, and for two genes mapping at 7p, IGF2BP3 and GRB10, the association with SRS turns out to be reinforced. The deleterious effect of the two potentially pathogenic variants, comprising GRB10 and ZNF331 genes, was explored by targeted approaches, though further studies are needed to validate their pathogenic role in the SRS etiology. In conclusion, we reconfirm the utility of performing a genome-wide scan to achieve a differential diagnosis in patients with SRS or similar features and to highlight novel chromosome alterations associated with SRS and growth retardation disorders.