Boosting BDNF in muscle rescues impaired axonal transport in a mouse model of DI-CMTC peripheral neuropathy.

Charcot-Marie-Tooth disease (CMT) is a genetic peripheral neuropathy caused by mutations in many functionally diverse genes. The aminoacyl-tRNA synthetase (ARS) enzymes, which transfer amino acids to partner tRNAs for protein synthesis, represent the largest protein family genetically linked to CMT aetiology, suggesting pathomechanistic commonalities. Dominant intermediate CMT type C (DI-CMTC) is caused by YARS1 mutations driving a toxic gain-of-function in the encoded tyrosyl-tRNA synthetase (TyrRS), which is mediated by exposure of consensus neomorphic surfaces through conformational changes of the mutant protein. In this study, we first showed that human DI-CMTC-causing TyrRSE196K mis-interacts with the extracellular domain of the BDNF receptor TrkB, an aberrant association we have previously characterised for several mutant glycyl-tRNA synthetases linked to CMT type 2D (CMT2D). We then performed temporal neuromuscular assessments of YarsE196K mice modelling DI-CMT. We determined that YarsE196K homozygotes display a selective, age-dependent impairment in in vivo axonal transport of neurotrophin-containing signalling endosomes, phenocopying CMT2D mice. This impairment is replicated by injection of recombinant TyrRSE196K, but not TyrRSWT, into muscles of wild-type mice. Augmenting BDNF in DI-CMTC muscles, through injection of recombinant protein or muscle-specific gene therapy, resulted in complete axonal transport correction. Therefore, this work identifies a non-cell autonomous pathomechanism common to ARS-related neuropathies, and highlights the potential of boosting BDNF levels in muscles as a therapeutic strategy.

Boosting BDNF in muscle rescues impaired axonal transport in a mouse model of DI-CMTC peripheral neuropathy.

Charcot-Marie-Tooth disease (CMT) is a genetic peripheral neuropathy caused by mutations in many functionally diverse genes. The aminoacyl-tRNA synthetase (ARS) enzymes, which transfer amino acids to partner tRNAs for protein synthesis, represent the largest protein family genetically linked to CMT aetiology, suggesting pathomechanistic commonalities. Dominant intermediate CMT type C (DI-CMTC) is caused by YARS1 mutations driving a toxic gain-of-function in the encoded tyrosyl-tRNA synthetase (TyrRS), which is mediated by exposure of consensus neomorphic surfaces through conformational changes of the mutant protein. In this study, we first showed that human DI-CMTC-causing TyrRSE196K mis-interacts with the extracellular domain of the BDNF receptor TrkB, an aberrant association we have previously characterised for several mutant glycyl-tRNA synthetases linked to CMT type 2D (CMT2D). We then performed temporal neuromuscular assessments of YarsE196K mice modelling DI-CMT. We determined that YarsE196K homozygotes display a selective, age-dependent impairment in in vivo axonal transport of neurotrophin-containing signalling endosomes, phenocopying CMT2D mice. This impairment is replicated by injection of recombinant TyrRSE196K, but not TyrRSWT, into muscles of wild-type mice. Augmenting BDNF in DI-CMTC muscles, through injection of recombinant protein or muscle-specific gene therapy, resulted in complete axonal transport correction. Therefore, this work identifies a non-cell autonomous pathomechanism common to ARS-related neuropathies, and highlights the potential of boosting BDNF levels in muscles as a therapeutic strategy.

Serum IL-31 is related to the severity and 3-month prognosis of patients with Intracerebral hemorrhage.

Interleukin (IL)-31/IL-33 axis has been proved to play an important role in the regulation of inflammation, and serum IL-33 was found to be a novel serum prognostic marker of intracerebral hemorrhage (ICH), while the value of serum IL-31 levels on prognosis in patients with ICH remains unknown. The present study was designed to study the value of serum IL-31 levels on prognosis in ICH patients. A total of 200 ICH patients and 50 healthy people were included in this study. We collected clinical data such as demographic data, laboratory data, admission disease scores and medical histories of these participants. We measured serum IL-31 levels using enzyme-linked immunosorbent assay, and assessed the prognosis of ICH patients 3 months after onset by mRS scale, and mRS > 2 was defined as a 3-month poor outcome. The level of IL-31 in ICH patients were significantly higher than that in healthy control people (211.91 ± 61.61 vs 167.64 ± 27.45 pg/mL, P < .001), and levels of IL-31 in ICH patients with 3-month good outcome were significantly lower than that in ICH patients with 3-month poor outcome (196.09 ± 50.84 vs 248.05 ± 41.41 pg/mL, P < .001). Results of correlation analysis suggested that the level of serum IL-31 was positively related to admission NIHSS score (r = 0.627, P < .001), hematoma volume (r = 0.352, P < .001), mRS score (r = 0.515, P < .001), high-density lipoprotein-cholesterol (r = 0.177, P = .012), serum C-reactive protein levels (r = 0.483, P < .001), and serum tumor necrosis factor α levels (r = 0.389, P < .001) in ICH patients, while the level of serum IL-31 was negatively related to the admission GCS score (r = -0.518, P < .001) and triglycerides (r = -0.147, P = .038). Results of multivariate regression analysis shows that serum IL-31 levels are an independent risk factor affecting NIHSS scores (OR = 1.023, 95% CI = 1.010-2.036) and 3-month prognosis (OR = 1.023, 95% CI = 0.982-1.747) in ICH patients. The receiver operating characteristic curve analysis showed that the sensitivity and specificity of serum IL-31 level in evaluating the prognosis of ICH were 85.2% and 76.7%, respectively. A cutoff value of serum IL-31 level > 185.30 pg/mL may indicate a poor prognosis for ICH. Serum IL-31 levels on admission in ICH patients are associated with patient prognosis, and higher serum IL-31 levels are associated with a higher risk of poor prognosis in ICH patients.

Risk factors for acute ischemic stroke in patients with type 2 diabetes mellitus.

To investigate the risk factors for acute ischemic stroke (AIS) in patients with type 2 diabetes mellitus (T2DM) patients. a total of 120 T2DM patients who met the inclusion and exclusion criteria, from between January 2021 to June 2022, were randomly selected and divided into T2DM and T2DM + AIS groups based on the presence or absence of a history of AIS. Blood samples were collected by fasting, 24 hours after admission, and levels of serum uric acid (UA), serum homocysteine (Hcy), serum creatinine (SCR), blood urea nitrogen (BUN), fasting blood glucose (FBG), glycated hemoglobin A1c (HbA1c), serum total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, high-sensitivity C-reactive protein (hs-CRP), and lipoprotein-associated phospholipase A2 (Lp-PLA2) were measured. Multivariate logistic regression analysis was performed for the significantly associated indicators to analyze the risk factors for AIS, and finally ROC curve analysis was carried out to explore the predictive value of the above risk factors for AIS in T2DM patients. the levels of FBG, Hcy, Hs-CRP and Lp-PLA2 were significantly higher in the T2DM + AIS group than those in T2DM group (P < .05). Multivariate logistic regression analysis revealed that hs-CRP and Lp-PLA2 were independent risk factors for the development of AIS in patients with T2DM with an OR of 2.85 (95% CI: 1.26-6.43, P = .012) and 3.64 (95% CI: 1.63-8.12, P = .002), respectively. ROC curve analysis showed that plasma hs-CRP and Lp-PLA2 showed good performance to predict AIS occurrence in T2DM patients (AUC = 0.749, 95% CI: 0.663, 0.835; and 0.791, 95% CI: 0.712, 0.870), with a sensitivity of 58.1% and 83.9%, and a specificity of 84.5% and 60.3%, respectively. The optimal concentration cutoff points of hs-CRP and Lp-PLA2 were 3.38 mg/L and 204.2 ng/mL. our findings suggested that plasma hs-CRP and Lp-PLA2 were independent risk factors for developing AIS in T2DM patients. Hs-CRP and Lp-PLA2 are potential biomarker for risk for AIS in patients with T2DM.

Plasma MMP-9/TIMP-1 ratio serves as a novel potential biomarker in Alzheimer's disease.

This study aimed to explore the diagnostic potential of plasma MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio for Alzheimer's disease (AD). This retrospective study was performed in a cohort consisting of patients with AD (AD group) and cognitive normal subjects (HC group). Cerebrospinal fluid (CSF) classic biomarkers including Aß42, Aß40, total tau (t-tau), and phosphorylated tau (p-tau) levels, and plasma MMP-9 and TIMP-1 levels were measured by commercially available ELISA kits, respectively. The differential diagnostic potential of plasma MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio was evaluated using the receiver operating characteristic curve analysis. It was observed that significantly elevated levels of plasma MMP-9 and MMP-9/TIMP-1 ratio in patients with AD than HC. Both MMP-9 and MMP-9/TIMP-1 ratios were negatively correlated with CSF Aß42/Aß40 ratio and positively correlated with CSF p-tau in AD group. ROC curve analysis showed better diagnostic accuracy of MMP-9/TIMP-1 ratio than MMP-9 for AD at a cutoff value of 1.35 with an area under the curve of 0.906 and sensitivity and specificity of 95.8% and 75%, respectively. Our findings encourage the use of plasma MMP-9/TIMP-1 ratio as a biomarker in the diagnosis of AD.

Effect of uncertain clinical conditions on the early healing and stability of distal radius fractures.

BACKGROUND AND OBJECTIVES: The healing outcomes of distal radius fracture (DRF) treated with the volar locking plate (VLP) depend on surgical strategies and postoperative rehabilitation. However, the accurate prediction of healing outcomes is challenging due to a range of certainties related to the clinical conditions of DRF patients, including fracture geometry, fixation configuration, and physiological loading. The purpose of this study is to investigate the influence of uncertainty and variability in fracture/fixation parameters on the mechano-biology and biomechanical stability of DRF, using a probabilistic numerical approach based on the results from a series of experimental tests performed in this study. METHODS: Six composite radius sawboneses fitted with titanium VLP (VLP 2.0, Austofix) were loaded to failure at a rate of 2 N/s. The testing results of the elastic and plastic behaviour of the VLP were used as inputs for a probabilistic-based computational model of DRF, which simulated mechano-regulated tissue differentiation and fixation elastic capacity at the fracture site. Finally, the probability of success in early indirect healing and fracture stabilisation was predicted. RESULTS: The titanium VLP is a strong and ductile fixation whose flexibility and elastic capacity are governed by flexion working length and bone-to-plate distance, respectively. A fixation with optimised designs and configurations is critical to mechanically stabilising the early fracture site. Importantly, the uncertainty and variability in fracture/fixation parameters could compromise early DRF healing. The physiological loading uncertainty is the most adverse factor, followed by the negative impact of uncertainty in fracture geometry. CONCLUSIONS: The VRP 2.0 fixation made of grade II titanium is a desirable fixation that is strong enough to resist irreparable deformation during early recovery and is also ductile to deform plastically without implant failure at late rehabilitation.

Panaxynol ameliorates cardiac ischemia/reperfusion injury by suppressing NLRP3-induced pyroptosis and apoptosis via HMGB1/TLR4/NF-κB axis.

BACKGROUND AND PURPOSE: Panaxynol (PNN) is a common natural minor component in Umbelliferae plants. Many clinical studies have shown that PNN exhibits nutritional value and anti-inflammatory and other pharmacological activities. However, whether PNN can mediate cardiac ischemia/reperfusion injury (IRI) remains unclear. Here, we aimed to determine the potential effects of PNN on myocardial IRI. METHODS: Myocardial IRI was stimulated in a mouse IRI model, and neonatal rat ventricle myocytes (NRVMs) were exposed to hypoxia/reoxygenation to construct in an vitro model. Myocardial infarction size, myocardial tissue injury, myocardial apoptotic index, hemodynamic monitoring, pyroptosis-related proteins, cardiac enzyme activities and inflammatory responses were examined to assess myocardial injury. RESULTS: It was found that PNN administration markedly reduced myocardial infarct size and apoptosis, suppressed myocardial damage and cell pyroptosis, attenuated pro-inflammatory cytokines and neutrophil infiltration via NLRP3 inhibitor. More importantly, PNN treatment remarkably decreased the expression of TLR4/NF-κB pathway-associated proteins and NLRP3-related pyroptosis proteins by HMGB1 inhibitor. PNN also enhanced cell viability, reduced cardiac enzyme activities, suppressed apoptosis and attenuated inflammation in the isolated NRVMs. Furthermore, vitro studies indicated that MCC950 (a NLRP3 inhibitor) increased the anti-inflammatory and anti-apoptotic effects of PNN on NRVMs via HMGB1/TLR4 pathway. CONCLUSION: To sum up, our results demonstrate that PNN exhibits a cardioprotective effect by modulating heart IRI-induced apoptosis and pyroptosis via HMGB1/TLR4/NF-κB pathway, thereby inhibiting NLRP3 inflammasome stimulation.

The Interrater and Intrarater Reliability of the Humeral Head Ossification System and the Proximal Femur Maturity Index Assessments for Patients with Adolescent Idiopathic Scoliosis.

Background: Skeletal maturity can evaluate the growth and development potential of children and provide a guide for the management of adolescent idiopathic scoliosis (AIS). Recent studies have demonstrated the advantages of the Humeral Head Ossification System (HHOS) and the Proximal Femur Maturity Index (PFMI), based on standard scoliosis films, in the management of AIS patients. We further assessed the HHOS and the PFMI method's reliability in the interrater and intrarater. Methods: The data from 38 patients, including the humeral head and proximal femur on standard scoliosis films, were distributed to the eight raters in the form of a PowerPoint presentation. On 38 independent standard spine radiographs, raters utilized the HHOS and PFMI to assign grades. The PPT sequence was randomly changed and then reevaluated 2 weeks later. For every system, the 95% confidence interval (95% CI) and intraclass correlation coefficient (ICC) were calculated to evaluate the interrater and intrarater reliability. Results: The HHOS was extremely reliable, with an intraobserver ICC of 0.802. In the first round, the interobserver ICC reliability for the HHOS was 0.955 (0.929-0.974), while in the second round, it was 0.939 (0.905-0.964). The PFMI was extremely reliable, with an intraobserver ICC of 0.888. In the first round, the interobserver ICC reliability for the PFMI was 0.967 (0.948-0.981), while in the second round, it was 0.973 (0.957-0.984). Conclusions: The HHOS and PFMI classifications had excellent reliability. These two methods are beneficial to reduce additional exposure to radiation and expense for AIS. There are advantages and disadvantages to each classification. Clinicians should choose a personalized and reasonable method to assess skeletal maturity, which will assist in the management of adolescent scoliosis patients.

Autoimmune encephalitis with posterior reversible encephalopathy syndrome: A case report.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a neuroimaging-based syndrome and is associated with multifocal vasogenic cerebral edema. Patients with PRES frequently demonstrate headache, seizure, encephalopathy, altered mental function, visual loss and so on. We here report a patient who showed persistent neurologic deficits after PRES and was ultimately diagnosed with autoimmune encephalitis (AE). CASE SUMMARY: This case exhibits a rare imaging manifestation of anti-casper 2 encephalitis which was initially well-matched with PRES and associated vasogenic edema. CONCLUSION: AE should be further considered when the etiology, clinical manifestations, and course of PRES are atypical.

Two-port robotic sleeve lobectomy using Stratafix sutures for central lung tumors.

OBJECTIVES: To explore the feasibility of two-port robotic sleeve lobectomy using Stratafix sutures for central lung tumors, and to summarize the surgical techniques and clinical outcomes. METHODS: We retrospectively evaluated 15 consecutive patients who underwent robotic bronchial sleeve lobectomy, performed by a single surgeon between March 2021 and September 2021. A half-continuous suture technique with two Stratafix sutures was used for bronchial anastomosis. The operative techniques and outcomes were analyzed. RESULTS: Complete resection was achieved in all patients undergoing different types of robotic bronchial sleeve lobectomy. There were no conversions to thoracotomy. The mean duration of surgery was 102.35 ± 46.31 min, mean time for bronchial anastomosis was 25.8 ± 15.2 min, mean blood loss was 64.71 ± 38.59 ml, and mean postoperative hospital stay was 4.76 ± 2.54 days. There was no death on follow-up within 90 days after surgery. CONCLUSIONS: Two-port robotic bronchial sleeve lobectomy and the novel anastomotic technique are both feasible and safe for selected patients.

The characteristics and treatment strategy for transolecranon fracture-dislocation of the elbow in children: a retrospective study.

BACKGROUND: Transolecranon fracture-dislocation of the elbow is rarely seen in children. The purpose of this retrospective study was to discuss the pathological characteristics and treatment strategy for this injury in children. METHODS: From October 2016 to March 2019, 15 patients seen and treated at our institutions for transolecranon fracture-dislocation of the elbow were identified, and their medical records and radiographs were reviewed retrospectively. There were 11 boys and 4 girls, with an average age of 8.3 years (from 5 to 14 years). The left arm was involved in 10 cases, and the right arm was involved in 5 cases. Type I (simple fracture) was found in 11 cases, and type II (comminuted fracture) was found in 4 cases, 3 of which with coronoid process involved. Closed reduction was successful under local anaesthesia in 14 cases but failed in 1 case. In 11 patients with type I fractures, 10 received fixation of Kirschner wire and tension band, and one patient underwent bone plate fixation. In 4 patients with comminuted fractures (type II), internal fixation was performed with Kirschner wires combined with reconstruction plates. RESULTS: The 15 patients were followed up for 24 to 48 months (average, 30.2 months). The final evaluation showed fine anatomical relationship of the elbow in all with no complications observed. Failure of internal fixation did not occur in any patient. The fractures acquired bony union in all patients after 8 to 12 weeks (average, 9.6 weeks). The therapeutic efficacy was evaluated at the final follow-up by the Mayo elbow performance score (MEPS) as excellent in 11 cases, good in 3 cases and fair in one case. CONCLUSIONS: As a type of complicated fracture-dislocation of the elbow, the transolecranon fracture-dislocation is rare in children. The fracture is mainly simple type. Treatment options depend on the type of fracture-dislocation. Only anatomical reduction of the olecranon fracture and restoration of a normal trochlear notch can lead to a stable humeroradial joint and good clinical efficacy.

First case of forearm crisscross injury in children: A case report.

BACKGROUND: Forearm crisscross injury is rare in children; there is no relevant literature so far. Surgeons lack experience and knowledge in treating this type of crisscross injury. We report a case of forearm crisscross injury in a child for the first time and analyze its mechanism. CASE SUMMARY: An 8-year-old boy experienced pain in his left forearm when he accidentally fell while skateboarding. Physical examination revealed swelling and deformity of the left forearm. We performed imaging and the results revealed left radial head dislocation, left distal radial epiphyseal separation from the shaft, and interruption of the continuity of the dorsal cortex of the left distal ulna. Anteroposterior and lateral X-ray films showed that the radius and ulna were crisscrossed. A diagnosis of superior radioulnar joint dislocation, left distal radial epiphyseal injury, and left distal ulnar fracture was made. After unsuccessful manual reduction, we adopted a minimally invasive procedure and succeeded. After a 14-wk period of follow-up, the patient had good left upper limb function, no complaints of pain or limited range of motion, and good follow-up results. CONCLUSION: This is the first report of a child with a forearm crisscross injury in which the mechanism and the differences from adult crisscross injury are analyzed. Minimally invasive surgery with intramedullary fixation can achieve a good therapeutic effect. This case provides a reference for the treatment of similar patients in the future.

Coinfection of Clostridium perfringens and Escherichia coli in gas-producing perianal abscess diagnosed by 16S rDNA sequencing: a case report.

BACKGROUND: Gas-producing perianal abscess raises the possibility of clostridial infection, with Clostridium perfringens being the most common causative agent, which is highly lethal if untreated timely. As the treatment of clostridial infections often differs from that of non-clostridial infections, which they may closely resemble, the importance of accurate pathogenic organism identification cannot be overemphasized. The 16S rDNA of bacteria is highly conserved within a species and among species of the same genus but demonstrates substantial variation between different species, thus making it a suitable genomic candidate for bacterial detection and identification. CASE PRESENTATION: Here, we report the case of a 53-year-old patient who was admitted to the hospital for a gas-producing perianal abscess. The patient was managed with ceftizoxime and ornidazole and then received debridement and drainage at the lesion on the second day after admission. The bacterial cultures of the patient isolates from the debridement showed a coinfection of Escherichia coli and Enterococcus faecium. Although perianal redness and swelling subsided obviously after the surgery, the patient was febrile to 38.3℃ with his left upper thigh red and swollen, aggravated with tenderness and crepitus. Considering insufficient debridement and the risk of incorrect identification of pathogens, a second debridement and drainage were performed 4 days after the primary operation, and 16S rDNA sequencing of the isolates implicated Clostridium perfringens infection. Given the discrepancies in diagnostic results and the treatment outcomes, Enterococcus faecium was identified as sample contamination, and a diagnosis of coinfection of Clostridium perfringens and Escherichia coli in gas-producing perianal abscess was confirmed. The patient was then successfully treated with meropenem and vancomycin and was discharged at 27 days of admission. CONCLUSIONS: This case represents the first report of coinfection of both clostridial and non-clostridial organisms in gas-producing perianal abscess and the first case reporting the use of 16S rDNA sequencing in the diagnosis of perianal abscess. Timely pathogen identification is critical for treating gas-producing perianal abscess and an antibiotic regimen covering both aerobic and anaerobic organisms is recommended before true pathogens are identified.

Surgical techniques and outcome analysis of uniportal video-assisted thoracic surgery complex sleeve lung resection: a 20 case-series study.

BACKGROUND: Our study aims to explore the feasibility of uniportal video-assisted complex sleeve lung resection and summarize the surgical techniques and clinical outcomes. METHODS: From June 2016 to April 2020, a total of 20 complex sleeve pulmonary and distal tracheal resections were performed by the single surgical team at the Thoracic Surgery Department of the Shanghai Pulmonary Hospital. We defined cases as complex sleeve pulmonary resections if they required pulmonary segment sleeve resection, extended sleeve resection (lobectomy plus segmentectomy of the remaining lobe), sleeve pneumonectomy, lobectomy plus carinoplasty or neo-carina construction, pulmonary-sparing main bronchus resection plus carina reconstruction, and distal trachea resection with end to end anastomosis. RESULTS: The 20 cases comprised lung squamous cell carcinoma (n=11), lung adenocarcinoma (n=2), hamartoma (n=3), adenoid cystic carcinoma (n=2), carcinoid tumor (n=1), and pleomorphic carcinoma (n=1). The average blood loss during the operation was 250±126.17 mL (50-800 mL). The average operation time was 192.0±61.1 minutes. The average number of lymph node stations removed was 5.82±1.33, including station seven in all cases, and the median number of lymph nodes removed was 4.18±5.89. On the day of surgery, the drainage volume was 266±192.01 mL. The mean postoperative hospital stay was 5.37±1.86 days. Twelve of the 16 patients diagnosed with malignancy received postoperative chemotherapy. Granuloma formation at the anastomosis level led to stenosis in one case, and tumor recurrence occurred in one case. Broncho-esophageal fistula occurred in one patient after radiochemotherapy. The postoperative follow-up time was 15.6±10.7 months. The 30-day mortality was zero, and at one-year follow-up, only one patient had died of metastatic disease after the operation. CONCLUSIONS: Uniportal video-assisted complex sleeve pulmonary resections are feasible when conducted by experienced teams.

Hydrothermal synthesis of a novel nanolayered tin phosphate for removing Cr(iii).

In this work, an outstanding nanolayered tin phosphate with 15.0 Å interlayer spacing, Sn (HPO4)2·3H2O (SnP-H+), has been synthesized by conventional hydrothermal method and first used in the adsorptive removal of Cr(iii) from aqueous solution. A number of factors such as contact time, initial concentration of Cr(iii), temperature, pH, and ionic strength on adsorption were investigated by batch tests. Moreover, the isothermal adsorption characteristics and kinetic model of Cr(iii) onto SnP-H+ were studied. The results showed that the adsorption of Cr(iii) by SnP-H+ was in accordance with the Langmuir adsorption isotherm model and the pseudo-second-order kinetic model. The adsorption capacity of Cr(iii) onto SnP-H+ at temperature 40.0 °C and pH 3.0 could reach 81.1 mg g-1. And the distribution coefficient K d was 23.0 g L-1. Overall, experiments certified that SnP-H+ was an excellent adsorbent that can effectively remove Cr(iii) from aqueous solution.

Content analysis of vitamins, dietary fibers and amino acids in a wide collection of barley (Hordeum vulgare L.) from Tibet, China.

Barley (Hordeum vulgare L.) is an important agricultural crop. Various studies on the genetic diversity, biochemical and molecular attributes on this species are known. However, information on nutritional variability in a large panel of barley cultivars is limited. Therefore, it is of interest for a quantitative analysis of vitamins, amino acids and dietary fibers in 245 barley of Tibet region in China. The coefficient of variation analysis revealed strong variation of vitamins (VB1>VB2>VE), essential amino acids (valine, histidine, methionine, lysine), non-essential amino acids (proline, tyrosine, cysteine), dietary fibers, (cellulose > lignin). Principal component analysis detected three clusters of cultivars, each with specific characteristics. However, the most nutritional cultivars were found in Cluster 3, which encompassed 52 cultivars. Distinctly, six cultivars (ZQ2000, BJX230, BJX229, BJX249, BJX191 and BJX265) were identified with highest nutritional values. This study reveals a large nutritional diversity in barley cultivars from Tibet and represents an important reference for the exploitation of these germplasm in crop improvement and breeding programmes.

Box-Behnken response surface approach to identify factors affecting membrane fouling in a hybrid membrane bioreactor treating domestic sewage.

The effect of hydraulic retention time (HRT) and sludge retention time (SRT) on extracellular polymer substrate (EPS) content and resistance of a hybrid membrane bioreactor (HMBR) treating domestic sewage was analyzed by Box-Behnken response surface methodology. The quadratic response surface model demonstrated significant effects of both HRT and SRT on EPS content (both P value < 0.05), SRT on membrane resistance (P value = 0.0119), and their interaction was significant (P value = 0.0273) for EPS but not membrane resistance (P value = 0.0609). Model optimization indicates that the optimal conditions for the HMBR to control membrane fouling were an HRT of 10 h and SRT of 30 days. Under these optimal conditions, both the EPS content and the predicted membrane resistance closely matched the actual average value with the error about 8%. Thus, the feasibility of applying response surface methodology to an HMBR for treating domestic sewage was demonstrated. According to the detection result of the three-dimensional fluorescence (excitation-emission matrix), humic acid-like and fulvic acid-like substances gain much higher levels in the suspended carriers than those in the membrane and sludge, suggesting that these are key components of the membrane pollutants. Graphical abstract .

Obesity and nonalcoholic fatty liver disease associated with adenocarcinoma in patients with lung cancer.

Lung cancer has become the leading cause of cancer-related deaths around the world. In addition to genetic risk factors and smoking, the metabolic risk factors remain to be elusive.To evaluate the associations between obesity, nonalcoholic fatty liver disease (NAFLD) and pulmonary adenocarcinoma in patients with lung cancer.Consecutive operation-proven lung cancer patients with assessment of metabolic disorders and liver ultrasound in 2009 and 2013 were retrospectively enrolled. T-test and multivariate logistic regression were applied to evaluate the contribution of individual factors to lung adenocarcinoma, as well as the synergistic effects between these factors.Among 3664 lung cancer patients with ultrasound examination, 2844 cases were enrolled for further analysis. Of them, 1053 (37.0%) were females, 1242 (43.7%) were cigarette smokers, 1658 (58.3%) were diagnosed as lung adenocarcinoma, 744 (26.2%) had obesity, and 614 (21.6%) had NAFLD. Proportion of female gender, nonsmoker, obesity, NAFLD, and serum lipid levels in patients with adenocarcinoma were significantly higher than those in other subtypes of lung cancer, and in 2013 than in 2009 (all P < .01). NAFLD and obesity were shown as independent factors and positively associated with pulmonary adenocarcinoma, along with female gender and nonsmoking, higher serum levels of cholesterol. NAFLD and other contributing factors exhibited no synergistic effects on adenocarcinoma.Obesity and NAFLD might increase the risk for pulmonary adenocarcinoma, especially in nonsmoking females, and underscore the need for further study into carcinogenic mechanisms and preventive interventions.

Silence of lncRNA MIAT protects ATDC5 cells against lipopolysaccharides challenge via up-regulating miR-132.

The over-expanding role of lncRNA myocardial infarction associated transcript (MIAT) in various human diseases has been recently revealed. This study attempted to see the role of MIAT in a cell model of osteoarthritis (OA). ATDC5 cells were subjected to lipopolysaccharides (LPS) to mimic a cell model of OA. The effects of MIAT on the model were tested by performing CCK-8 assay, flow cytometry, qRT-PCR, western blot and ELISA. The downstream miRNA and signalling pathways were studied by utilizing qRT-PCR and western blot. Transfection of ATDC5 cells with the shRNA specific against MIAT significantly attenuated LPS-evoked apoptosis and cytokines release. At the meantime, the viability loss and the cleavage of caspases were ameliorated as well. MIAT overexpressed lead to the opposite result. Further, miR-132 was found to be negatively regulated by MIAT. The protective effects of MIAT silence were flattened when miR-132 expression was suppressed. Besides that the inhibitory effects of MIAT silence on LPS-evoked NF-κB and JNK activation were eliminated by miR-132 silence. This study illustrated that silence of MIAT protected ATDC5 cells against LPS challenge. The chondroprotective effects of MIAT silence may be via up-regulation of miR-132 and inhibition of NF-κB and JNK pathways.

Axial length/corneal radius of curvature ratio and refractive development evaluation in 3- to 4-year-old children: the Shanghai Pudong Eye Study.

AIM: To measure and analysis axial length (AL)/corneal radius of curvature (CRC) ratio and other refractive parameters, provide a medical reference range for refractive development evaluation and earlier visual impairment screening of 3 to 4y kindergarten students. METHODS: Between April and June 2017, a total of 4350 participants aged 3- to 4-year-old (8700 eyes) from 10 cluster random sampling kindergartens in Shanghai, Pudong District were involved. According to the measurement and analysis of the unaided visual acuity (VA), AL, CRC, AL/CRC ratio, astigmatism and other refractive parameters, the data distribution and reference range were obtained. RESULTS: Uncorrected VA of examined children was 0.23±0.08 (logMAR, mean±SD) [95% confidence interval (CI) range ≤0.36]; AL was 22.10±0.79 mm (95%CI 20.55-23.65); CRC was 7.86±0.26 mm (95%CI, 7.35-8.37); AL/CRC ratio was 2.81±0.12 (95%CI, 2.57-3.05). The median of astigmatism was -0.5 D, a total of 56.3% had astigmatism <-0.50 D, 85.3%<-1.00 D, 6.7%>-1.50 D; 71% were astigmatism with the rule. Eye-specific analyses were conducted. Statistical difference of VA was in right and left eyes. There were no significant differences between two eyes of AL, CRC, AL/CRC ratio and astigmatism (P>0.05). CONCLUSION: VA and AL/CRC ratio reference could be used to assess refractive development in children and screening uncorrected refractive errors or amblyopia. Astigmatism needs to be considered in the diagnosis.