SPINT2 mutations in the Kunitz domain 2 found in SCSD patients inactivate HAI-2 as prostasin inhibitor via abnormal protein folding and N-glycosylation.

Mutations in the Kunitz-type serine protease inhibitor HAI-2, encoded by SPINT2, are responsible for the pathogenesis of syndromic congenital sodium diarrhea (SCSD), an intractable secretory diarrhea of infancy. Some of the mutations cause defects in the functionally required Kunitz domain 1 and/or subcellular targeting signals. Almost all SCSD patients, however, harbor SPINT2 missense mutations that affect the functionally less important Kunitz domain 2. How theses single amino acid substitutions inactivate HAI-2 was, here, investigated by the doxycycline-inducible expression of three of these mutants in HAI-2-knockout Caco-2 human colorectal adenocarcinoma cells. Examining protein expressed from these HAI-2 mutants reveals that roughly 50% of the protein is synthesized as disulfide-linked oligomers that lose protease inhibitory activity due to the distortion of the Kunitz domains by disarrayed disulfide bonding. Although the remaining protein is synthesized as monomers, its glycosylation status suggests that the HAI-2 monomer remains in the immature, lightly glycosylated form, and is not converted to the heavily glycosylated mature form. Heavily glycosylated HAI-2 possesses full anti-protease activity and appropriate subcellular targeting signals, including the one embedded in the complex-type N-glycan. As predicted, these HAI-2 mutants cannot suppress the excessive prostasin proteolysis caused by HAI-2 deletion. The oligomerization and glycosylation defects have also been observed in a colorectal adenocarcinoma line that harbors one of these SPINT2 missense mutations. Our study reveals that the abnormal protein folding and N-glycosylation can cause widespread HAI-2 inactivation in SCSD patents.

A systematic review and meta-analysis of canine enteric coronavirus prevalence in dogs of mainland China.

BACKGROUND: Canine enteric coronavirus (CECoV) is a prevalent infectious disease among dogs worldwide, yet its epidemiology in mainland China remains poorly understood. This systematic review and meta-analysis aimed to assess the prevalence of CECoV in mainland China and identify factors influencing its prevalence. METHODS: A comprehensive literature search was conducted across multiple databases for studies regarding CECoV epidemiology of China. PubMed, CNKI, Wanfang, and CQVIP were searched to obtain the studies. Eligible studies were selected based on predefined criteria, and data were extracted and synthesized. The quality the studies was assessed using the JBI assessment tool. Heterogeneity was checked using I2 test statistics followed by subgroup and sensitivity analysis. Subgroup analyses were performed to explore variations in CECoV prevalence by factors such as year, region, season, health status, social housing type, gender, age, and breed. Publication bias was assessed using a funnel plot and eggers test that was followed by trim and fill analysis. RESULTS: A total of 27 studies involving 21,034 samples were included in the meta-analysis. The overall pooled prevalence of CECoV in mainland China was estimated to be 0.30 (95% CI 0.24-0.37), indicating persistent circulation of the virus. Subgroup analyses revealed higher prevalence rates in younger dogs, multi-dog households, apparently healthy dogs, and certain regions such as southwest China. Seasonal variations were observed, with lower prevalence rates in summer. However, no significant differences in prevalence were found by gender. CONCLUSIONS: This study provides valuable insights into the epidemiology of CECoV in mainland China, highlighting the persistent circulation of the virus and identifying factors associated with higher prevalence rates. Continuous monitoring and surveillance efforts, along with research into accurate detection methods and preventive measures, are essential for the effective control of CECoV and mitigation of its potential impact on animal and human health.

Anatomical Study of the Superior Auricular Artery Using 3-Dimensional Computed Tomography Angiography.

BACKGROUND: The superior auricular artery (SAA)-retroauricular flap is commonly used for the repair of defects of the superior auricle. There are few studies about the anatomy of the SAA. OBJECTIVE: This study mainly analyzed the anatomical pattern of SAA. MATERIALS AND METHODS: Computed tomography (CT) was performed on 26 cadaver heads infused with lead oxide. The anatomical pattern of the SAA was statistically analyzed by 3-dimensional CT images. RESULTS: The SAA was classified into 3 types according to whether it gave off the helix branch or the auricular dorsal branch. The SAA was located mainly in an area 2 cm above and below the horizontal line at the midpoint of the 2 base points (the otobasion superius and the apex of the external auditory canal). The origin of each branch of the SAA was mainly located in Areas 2, 3, and 4 within a circular area that had the otobasion superius as the center of the circle and a radius of 2 cm. CONCLUSION: In this study, the 3 anatomical types and anatomical patterns of the SAA were identified. These findings can provide a reference for the design of SAA-retroauricular flaps and for surgical planning.

N-glycosylation on Asn-57 is required for the correct HAI-2 protein folding and protease inhibitory activity.

Hepatocyte growth factor activator inhibitor (HAI)-2 is an integral membrane Kunitz-type serine protease inhibitor that regulates the proteolysis of matriptase and prostasin in a cell-type selective manner. The cell-type selective nature of HAI-2 function depends largely on whether the inhibitor and potential target enzymes are targeted to locations in close proximity. The N-glycan moiety of HAI-2 can function as a subcellular targeting signal. HAI-2 is synthesized with 1 of 2 different N-glycan modifications: one of oligomannose-type, which largely remains in the endoplasmic reticulum/GA, and another of complex-type, which is targeted toward the apical surface in vesicle-like structures, and could function as an inhibitor of matriptase and prostasin. HAI-2 contains 2 putative N-glycosylation sites, Asn-57 and Asn-94, point mutations of which were generated and characterized in this study. The protein expression profile of the HAI-2 mutants indicates that Asn-57, and not Asn-94, is responsible for the N-glycosylation of both HAI-2 species, suggesting that the form with oligomannose-type N-glycan is the precursor of the form with complex-type N-glycan. Unexpectedly, the vast majority of non-glycosylated HAI-2 is synthesized into multiple disulfide-linked oligomers, which lack protease inhibitory function, likely due to distorted conformations caused by the disarrayed disulfide linkages. Although forced expression of HAI-2 in HAI-2 knockout cells artificially enhances HAI-2 oligomerization, disulfide-linked HAI-2 oligomers can also be observed in unmodified cells. These results suggest that N-glycosylation on Asn-57 is required for folding into a functional HAI-2 with full protease suppressive activity and correct subcellular targeting signal.

Association of systemic immune inflammatory index with all-cause and cause-specific mortality among individuals with type 2 diabetes.

BACKGROUND: The evidence regarding the association between the systemic immune inflammatory index (SII) and mortality among individuals with diabetes is limited. This study aims to evaluate the associations between SII and all-cause and cause-specific mortality among individuals with diabetes. METHODS: The study included 8,668 participants with diabetes from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 with follow-up until 31 December 2019. The calculation of SII in this study was performed using the following formula: the neutrophil-to-lymphocyte ratio multiplied by the platelet count (10^9 cells/µL). RESULTS: The study documented 2,463 deaths over 68,542 person-years, including 853 deaths from CVD and 424 from cancer. An increase in SII was significantly associated with higher all-cause and CVD mortality risk after multivariate adjustment. For each standard deviation increment in natural log transformed SII (lnSII), all-cause mortality increased by 17%, and CVD mortality increased by 34% (both P < 0.001). Additionally, the association between SII and all-cause mortality was U-shaped, with the inflection point at 6.02. The association between SII and CVD mortality was non-linear and J-shaped, where the risk increased significantly when lnSII exceeded 6.22. Furthermore, the association between SII and CVD mortality was attenuated in female and hyperlipidemia patients. CONCLUSION: In this study, we observed a significant positive association between the SII and both all-cause and CVD mortality in patients with diabetes. Additionally, it was discovered that this association exhibited a non-linear pattern. These findings suggest that maintaining SII within an optimal range may play a critical role in mitigating the risk of mortality.

Comparative efficacy and safety of disease-modifying therapies in patients with relapsing multiple sclerosis: A systematic review and network meta-analysis.

BACKGROUND: Currently, 19 disease-modifying therapies (DMTs) have been approved for the treatment of patients with relapsing forms of multiple sclerosis (RMS). OBJECTIVE: The objective of this study was to conduct a systematic review and network meta-analysis to evaluate the efficacy and safety of DMTs in adults with RMS. METHODS: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the Food and Drug Administration, and European Medicines Agency websites for randomized controlled trials (RCTs) (from inception to July 2021). Eligible RCTs evaluated approved treatments for RMS as monotherapy and reported at least one of the primary outcome measures of interest. The primary outcome was efficacy (annualized relapse rate and 12-week confirmed disability progression) and safety (serious adverse events [AEs] and discontinuation due to AEs). We assessed the risk of bias (RoB) of included studies using the Cochrane RoB tool version 2.0 (https://www.bmj.com/content/343/bmj.d5928) for RCTs. Surface under the cumulative ranking (SUCRA) was used to rank therapies and to assess quality of general evidence, respectively. The Grading of Recommendations Assessment, Development and Evaluation framework was used to rank therapies and to assess quality of general evidence. RESULTS: A total of 43 records represent 45 RCTs selected for network meta-analysis. In total, 30,720 participants (median of 732; interquartile range: 248-931) were included, of which 67% were female. By SUCRA analysis, alemtuzumab (94.3%) presented the highest probability of being the best alternative for annualized relapse rate, whereas ofatumumab (93.5%) presented the highest probability of being the best alternative for 12-week confirmed disability progression. Interferon beta-1b subcutaneous (87.0%) presented the highest probability of the best safety among all DMTs for serious AEs, whereas alemtuzumab (92.4%) presented the highest probability of the best safety among all DMTs for discontinuation due to AEs. CONCLUSION: Network meta-analysis shows that alemtuzumab and ofatumumab present the highest efficacy among DMTs. Because there is little difference between these probabilities for many treatments, health professionals should use clinical shared decision making when formulating treatment plans with patients.

Integrated lactic acid production from lignocellulosic agricultural wastes under thermal conditions.

The production of lactic acid (LA) from agricultural wastes attracts great attention because of the sustainability and abundance of lignocellulosic feedstocks, as well as the increasing demand for biodegradable polylactic acid. In this study, we isolated a thermophilic strain Geobacillus stearothermophilus 2H-3 for use in robust production of L-(+)LA under the optimal conditions of 60 °C, pH 6.5, which were consistent with the whole-cell-based consolidated bio-saccharification (CBS) process. Sugar-rich CBS hydrolysates derived from various agricultural wastes, including corn stover, corncob residue, and wheat straw, were used as the carbon sources for 2H-3 fermentation by directly inoculating 2H-3 cells into the CBS system, without intermediate sterilization, nutrient supplementation, or adjustment of fermentation conditions. Thus, we successfully combined two whole-cell-based steps into a one-pot successive fermentation process to efficiently produce LA with high optical purity (99.5%), titer (51.36 g/L), and yield (0.74 g/gbiomass). This study provides a promising strategy for LA production from lignocellulose through CBS and 2H-3 fermentation integration.

Nonsteroidal anti-inflammatory drugs associated acute kidney injury in hospitalized children: A systematic review and meta-analysis.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are regarded as nephrotoxins. Children commonly use NSAIDs and are susceptible to nephropathy, but the relationship between acute kidney injury (AKI) and use of NSAIDs is not well examined yet. OBJECTIVE: To evaluate the relationship between AKI and use of NSAIDs in hospitalized pediatric patients who are susceptible to nephropathy. METHODS: We conducted this systematic review and meta-analysis of observational studies by searching PubMed, Embase, and Cochrane Database for articles published up to June 1, 2020. Reports included involved children (age < 18 years) who used NSAIDs for various reasons and were admitted in the hospital. The main outcome measure was whether AKI occurred, and pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated using generic inverse variance methods. RESULTS: Seven studies reporting risk of AKI in the hospitalized pediatric patients receiving NSAIDs were included applying a random-effects model. In the hospitalized pediatric population, the pooled OR of AKI for present NSAID exposure was 1.55 (95%CI 1.26-1.92). CONCLUSIONS: NSAID exposure was associated with an approximate 1.6-fold rise in the odds of developing AKI in hospitalized pediatric patients. Avoidance, cautious use of NSAIDs and further evidence are needed. This study was registered with PROSPERO (identifier: CRD42021219779).

The RNA N6 -methyladenosine modulator HNRNPA2B1 is involved in the development of non-small cell lung cancer.

The key N6  methyladenosine (m6 A) RNA methylation regulator is associated with multiple tumour progression. However, the m6 A-associated regulators that influence non-small cell lung cancer (NSCLC) development have not been fully clarified. The m6 A regulator expression pattern of NSCLC patients from The Cancer Genome Atlas (TCGA) dataset was identified. Aberrations of m6A modulators are related to NSCLC development via cBioPortal database. Furthermore, we found that IGF2BP2, IGF2BP3, HNRNPA2B1, and FTO are significantly correlated with advanced stage disease or clinical outcomes in NSCLC by UALCAN and Kaplan-Meier plot. Bioinformatics analysis showed that m6 A modulators (IGF2BP2, IGF2BP3, HNRNPA2B1, and FTO) are associated with immunomodulator and immune infiltration expression in NSCLC via the Tumor Immune Estimation Resource (TIMER) database. The co-expression between these m6A-associated modulators was analysed by protein-protein interaction networks. Finally, we found that HNRNPA2B1 promotes NSCLC development in vitro by regulating cell proliferation and metastasis functions via Cell Counting Kit 8 (CCK8) and transwell assay. Our study showed that HNRNPA2B1 is a promising target and biomarker for cancer therapy in NSCLC.

Computer Vision and Machine Learning-Based Gait Pattern Recognition for Flat Fall Prediction.

BACKGROUND: Gait recognition has been applied in the prediction of the probability of elderly flat ground fall, functional evaluation during rehabilitation, and the training of patients with lower extremity motor dysfunction. Gait distinguishing between seemingly similar kinematic patterns associated with different pathological entities is a challenge for the clinician. How to realize automatic identification and judgment of abnormal gait is a significant challenge in clinical practice. The long-term goal of our study is to develop a gait recognition computer vision system using artificial intelligence (AI) and machine learning (ML) computing. This study aims to find an optimal ML algorithm using computer vision techniques and measure variables from lower limbs to classify gait patterns in healthy people. The purpose of this study is to determine the feasibility of computer vision and machine learning (ML) computing in discriminating different gait patterns associated with flat-ground falls. METHODS: We used the Kinect® Motion system to capture the spatiotemporal gait data from seven healthy subjects in three walking trials, including normal gait, pelvic-obliquity-gait, and knee-hyperextension-gait walking. Four different classification methods including convolutional neural network (CNN), support vector machine (SVM), K-nearest neighbors (KNN), and long short-term memory (LSTM) neural networks were used to automatically classify three gait patterns. Overall, 750 sets of data were collected, and the dataset was divided into 80% for algorithm training and 20% for evaluation. RESULTS: The SVM and KNN had a higher accuracy than CNN and LSTM. The SVM (94.9 ± 3.36%) had the highest accuracy in the classification of gait patterns, followed by KNN (94.0 ± 4.22%). The accuracy of CNN was 87.6 ± 7.50% and that of LSTM 83.6 ± 5.35%. CONCLUSIONS: This study revealed that the proposed AI machine learning (ML) techniques can be used to design gait biometric systems and machine vision for gait pattern recognition. Potentially, this method can be used to remotely evaluate elderly patients and help clinicians make decisions regarding disposition, follow-up, and treatment.

Significance of Hypermethylation of Tumor-Suppressor Genes PTGER4 and ZNF43 at CpG Sites in the Prognosis of Colorectal Cancer.

The status of DNA methylation in primary tumor tissue and adjacent tumor-free tissue is associated with the occurrence of aggressive colorectal cancer (CRC) and can aid personalized cancer treatments at early stages. Tumor tissue and matched adjacent nontumorous tissue were extracted from 208 patients with CRC, and the correlation between the methylation levels of PTGER4 and ZNF43 at certain CpG loci and the prognostic factors of CRC was determined using the MassARRAY System testing platform. The Wilcoxon signed-rank test, a Chi-square test, and McNemar's test were used for group comparisons, and Kaplan-Meier curves and a log-rank test were used for prediction. The hypermethylation of PTGER4 at the CpG_4, CpG_5, CpG_15, and CpG_17 tumor tissue sites was strongly correlated with shorter recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) [hazard ratio (HR) = 3.26, 95% confidence interval (CI) = 1.38-7.73 for RFS, HR = 2.35 and 95% CI = 1.17-4.71 for PFS, HR = 4.32 and 95% CI = 1.8-10.5 for OS]. By contrast, RFS and PFS were significantly longer in the case of increased methylation of ZNF43 at the CpG_5 site of normal tissue [HR = 2.33, 95% CI = 1.07-5.08 for RFS, HR = 2.42 and 95% CI = 1.19-4.91 for PFS]. Aberrant methylation at specific CpG sites indicates tissue with aggressive behavior. Therefore, the differential methylation of PTGER4 and ZNF43 at specific loci can be employed for the prognosis of patients with CRC.

Combined Ileoileal and Ileocolic Intussusception Secondary to Inflammatory Fibroid Polyp in an Adult: A Case Report.

Intestinal intussusception is relatively rare in adults and accounts for approximately 5% of intestinal obstruction. Intussusception is classified into subtypes according to the location, including ileoileal, ileocolic, ileo-ileocolic, colo-colic, jejuno-ileal, or jejuno-jejunal; the ileocolic type being the most common. However, intussusception of a combination of different subtypes has rarely been reported in the available literature. Abdominal computed tomography (CT) is the most accurate tool to evaluate intestinal intussusception. The pathological lead point in the intestine typically results in adult intussusception. Surgical intervention is usually adopted in cases of adult intussusception due to a high incidence of underlying bowel malignancy. An inflammatory fibroid polyp (IFP) is one of the uncommon benign neoplasms of the gastrointestinal (GI) system, which can result in intestinal intussusception. Herein, we present a case of a 50-year-old female with combined ileoileal and ileocolic intussusception, which was initially diagnosed by abdominal CT. Therefore, laparoscopic right hemicolectomy surgery was performed, confirming the final diagnosis as ileoileal and ileocolic intussusception secondary to IFP.

Duodenal Ulcer with Massive Gastrointestinal Hemorrhage as an Initial Manifestation in Multiple Myeloma with Extramedullary Disease: A Case Report.

Plasma cell neoplasms are characterized by dysregulated proliferation of mature B cells, which can present with either single (solitary plasmacytoma) or systemic (multiple myeloma (MM)) involvement. MM with extramedullary plasmacytoma (EMP) is a rare disease that accounts for approximately 3-5% of all plasmacytomas. EMP with gastrointestinal (GI) system involvement is an even rarer entity, accounting for <1% of MM cases. We present a case of aggressive MM with EMP invading the duodenum, initially presented with massive upper GI hemorrhage and small bowel obstruction. A 67-year-old woman was admitted to our hospital owing to a lack of either gas or feces passage for 3 days. Abdominal distention and vomit with a high coffee ground content were observed for 24 h. The patient's condition was initially diagnosed as small bowel obstruction, upper gastrointestinal bleeding, severe anemia, acute renal failure, and hypercalcemia. Furthermore, an analysis of immunoelectrophoresis in the blood, bone marrow aspiration, and tissue biopsy supported the diagnosis of MM and EMP invading the duodenum, upper GI hemorrhage, and small bowel obstruction. Our study provided the possible involvement of MM and EMP in the differential diagnosis of patients with unexplained GI hemorrhage and small bowel obstruction. A thorough review of the literature regarding the association between MM, GI hemorrhage, and small bowel obstruction is presented in this study.

Human Papillomavirus and Risk of Colorectal Cancer: An Analysis of Nationwide Claims Data.

Background and Objectives: Although human papillomavirus (HPV) is a major etiology of cervical and anogenital cancers, whether it is associated with colorectal carcinogenesis is yet undetermined. Materials and Methods: The longitudinal association of HPV infection with colorectal cancer (CRC) was evaluated using 2000-2013 data from a nationwide Taiwanese claims database. In this retrospective cohort study, 358 patients with primary HPV diagnoses (HPV-infected cohort) and 1432 patients without such a diagnosis (HPV-uninfected cohort) were recruited between 2000 and 2006. Both cohorts were followed up to identify CRC incidences from 2006 to 2013. Hazard ratios (HRs) and their 95% confidence intervals (CIs) derived from Cox proportional hazards models were used to estimate the association between HPV and CRC risk. Results: The HPV-infected cohort had a significantly higher cumulative incidence of CRC than the HPV-uninfected cohort. The presence of HPV was associated with an increased risk of CRC (adjusted HR, 1.63; 95% CI, 1.02-3.62). Furthermore, the significant HPV-CRC risk association was evident in both sexes. Conclusions: This population-based cohort study reveals longitudinal evidence that HPV is associated with an increased risk of CRC. Further studies are required to verify the role of HPV in colorectal carcinogenesis.

Association between gastroesophageal reflux disease and colorectal cancer risk: a population-based cohort study.

PURPOSE: Several studies have investigated the association between gastroesophageal reflux disease (GERD) and colorectal cancer (CRC) risk, but the presented scientific results are highly debatable. This study examined the longitudinal association between GERD and CRC in an Asian population. METHODS: A retrospective cohort study was performed using the National Health Insurance Research Database of Taiwan. The study cohort comprised 45,828 individuals with newly diagnosed GERD (the GERD cohort) and 229,140 age, sex, and date of enrollment-matched patients without GERD (the comparison cohort) from 2000 to 2006. The primary outcome was the incidence of CRC. To estimate the effect of GERD on the risk of CRC, the Cox proportional hazards model was fitted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: There were 785 newly diagnosed CRC patients in the 45,828 patients with GERD. Relatively, there were 2375 incident CRC cases in 229,140 patients without GERD. The incidence rate of CRC for the GERD cohort (17.60 per 10,000 person-years) was significantly higher than the corresponding incidence rate for the comparison cohort (10.22 per 10,000 person-years). After adjustment for confounders, GERD was associated with a significantly increased risk of CRC (adjusted HR,1.76; 95% CI, 1.62-2.90). Of note, a significant association between GERD and CRC risk was evident in both genders. CONCLUSIONS: In conclusion, this nationwide population-based cohort study supports the hypothesis that GERD was associated with a significantly increased risk of CRC. Our findings warrant still further investigation of the underlying mechanisms related to carcinogenic effect of GERD on colorectal carcinoma.

Efficacy and Safety of Eculizumab for Paroxysmal Nocturnal Hemoglobinuria: A Systematic Review and Meta-Analysis.

BACKGROUND: Eculizumab is indicated for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). This study aimed to evaluate the efficacy and safety of eculizumab in patients with PNH. METHODS: PubMed, EMBASE, The Cochrane Library, and ClinicalTrials.gov were searched for prospective interventional studies treating PNH with eculizumab. The primary outcome was the change in lactate dehydrogenase (LDH) levels, whereas secondary outcomes included the change in hemoglobin (Hb) levels, transfusion rates, and adverse drug events. RESULTS: Patients (n=235) from 6 studies were included in this meta-analysis. LDH and Hb levels and transfusion rates decreased significantly at 12, 26 weeks, 12, 15, and >15 months. The most frequent adverse events included nasopharyngitis (effect size [ES]: 0.53; 95% confidence intervals [CI]: 0.47 to 0.60; P=0.00), headache (ES: 0.47; 95% CI: 0.25 to 0.69; P=0.00), upper respiratory tract infection (ES: 0.37; 95% CI: 0.27 to 0.46; P=0.00), nausea (ES: 0.31; 95% CI: 0.24 to 0.38; P=0.00), fatigue, diarrhea, cough, pyrexia, abdominal pain, pain in extremities, and contusion. CONCLUSION: Eculizumab is an effective and well-tolerated treatment for patients with PNH. It is effective at decreasing LDH levels and transfusion rates while increasing Hb levels. Further studies are needed to explore the safety of eculizumab.

Salvianolic acid A blocks vasculogenic mimicry formation in human non-small cell lung cancer via PI3K/Akt/mTOR signalling.

Vasculogenic mimicry (VM) is associated with aggressive cancer cells. Salvianolic acid A (Sal-A), an antioxidant and anti-inflammatory agent, has bioactive properties from Salvia miltiorrhiza Bunge. Current investigation aspired to explore the activity of Sal-A in the VM formation of non-small cell lung cancer (NSCLC) and the mechanism underling this function. The CCK8, the scratch and boyden chemotaxis assay were presented to describe NSCLC cells viability, migration and invasion capabilities, respectively. The protein expression was verified by western blotting. In this report, Sal-A caused a reduction in viability, metastasis and capillaries structure formation of NSCLC cells. Additionally, Sal-A markedly prevented the key VM related proteins, containing EphA2, VE-cadherin and MMP2. Besides, Sal-A significantly diminished p-PI3K, p-Akt and p-mTOR level in NSCLC cells. More importantly, SC79 pretreatment reversed Sal-A inhibits NSCLC cells viability, metastasis and VM formation. These data exhibit that Sal-A could block VM network formation in NSCLC cells through modulating the PI3K/Akt/mTOR signalling pathway.

Physeal-sparing posteromedial portal approach reduced distance between guide pin and neurovascular structures.

PURPOSE: To compare a femoral physeal sparing anterior cruciate ligament (ACL) reconstruction technique utilizing a posteromedial portal to traditional transphyseal techniques with regards to anatomic tunnel positioning and proximity to important neurovascular structures. METHODS: Eight cadaveric knees were obtained for the study. Femoral tunnel guide pins were placed utilizing four different techniques: accessory anterior medial portal, posteromedial portal, trans-tibial, and figure-4 methods. The knees were then dissected and the following measurements taken: distance of each pin to the saphenous and peroneal nerve, popliteus tendon, neurovascular bundle, femoral ACL footprint and articular cartilage, and the angle of the guide pin entering the lateral femoral condyle. Fluoroscopic imaging was taken to determine the disruption of the physeal scar. RESULTS: Posteromedial portal guide pin was significantly closer to the neurovascular bundle, popliteal tendon and saphenous nerve when compared to the other 3 techniques, but was further from the peroneal nerve. It also had the smallest distance from the anatomic footprint of the ACL, and the largest angle to the lateral femoral condyle. The posteromedial portal guide pin had similar distance from the articular cartilage as the accessory anterior medial portal and figure-4 guide pin, with the trans-tibial guide pin being the farthest. The posteromedial portal guide pin failed to disrupt the physeal scar in all specimens, while the other three techniques consistently violated the physeal scar. CONCLUSION: The posteromedial portal technique offers an appropriate method for anatomic ACL reconstruction while protecting the distal femoral physis from injury. Care needs to be taken with this technique as it comes in closer proximity to some of the important neurovascular structures. This study indicates that posteromedial portal technique is a less technically challenging approach for physeal-sparing ACL repair with special attention required for the protection of neurovascular bundle from potential injury.

Bifurcation and chaos analysis for a discrete ecological developmental systems.

This work concentrates on the dynamic analysis including bifurcation and chaos of a discrete ecological developmental systems. Specifically, it is a prey-predator-scavenger (PPS) system, which is derived by Euler discretization method. By choosing the step size h as a bifurcation parameter, we determine the set consists of all system's parameters, in which the system can undergo flip bifurcation (FB) and Neimark-Sacker bifurcation (NSB). The theoretical results are verified by some numerical simulations. It is shown that the discrete systems exhibit more interesting behaviors, including the chaotic sets, quasi-periodic orbits, and the cascade of period-doubling bifurcation in orbits of periods 2, 4, 8, 16. Finally, corresponding to the two bifurcation behaviors discussed, the maximum Lyapunov exponent is numerically calculated, which further verifies the rich dynamic characteristics of the discrete system.

Precision and accuracy of commercial assays for vancomycin therapeutic drug monitoring: evaluation based on external quality assessment scheme.

BACKGROUND: Vancomycin remains a mainstay of the treatment of Gram-positive bacterial infections. It is crucial to accurately determine vancomycin serum concentration for adequate dose adjustment. OBJECTIVES: To evaluate the precision and accuracy of commercial assay techniques for vancomycin concentration and to assess the comparability of vancomycin detection methods in Chinese laboratories. METHODS: Human serum samples spiked with known concentrations of vancomycin were provided to laboratories participating in the external quality assessment scheme (EQAS). Assay methods included chemiluminescence, enzyme immunoassay (EIA) and so on. The dispersion of the measurements was analysed and the robust coefficient of variation (rCV), relative percentage difference (RPD) and satisfactory rate for method groups were calculated. Moreover, performance of the Chinese laboratories was assessed. RESULTS: A total of 657 results from 75 laboratories were collected, including 84 samples from 10 Chinese laboratories. The median rCV, median RPD and satisfactory rates classified by methods ranged from 1.85% to 15.87%, -14.75% to 13.34% and 94.59% to 100.00%, respectively. Significant differences were seen in precision, between kinetic interaction of microparticles in solution (KIMS) and other methods, and in accuracy, between enzyme-multiplied immunoassay technique (EMIT), fluorescence polarization immunoassay (FPIA) and other techniques. Vancomycin detection in China mainly depended on the chemiluminescence and EMIT methods, which tended to result in lower measurements. CONCLUSIONS: Although almost all assays in this study achieved an acceptable performance for vancomycin serum concentration monitoring, obvious inconsistencies between methods were still observed. Chinese laboratories were more likely to underestimate vancomycin concentrations. Thus, recognizing inconsistencies between methods and regular participation in vancomycin EQAS are essential.