Preoperative pancreatic stent placement before the enucleation of insulinoma located in the head and neck of the pancreas in proximity to the main pancreatic duct: study protocol for a multicentre randomised clinical trial in Chinese tertiary medical centres.

INTRODUCTION: The surgical intervention approach to insulinomas in proximity to the main pancreatic duct remains controversial. Standard pancreatic resection is recommended by several guidelines; however, enucleation (EN) still attracts surgeons with less risk of late exocrine/endocrine insufficiency, despite a higher postoperative pancreatic fistula (POPF) rate. Recently, the efficacy and safety of preoperative pancreatic stent placement before the EN have been demonstrated. Thus, a multicentre open-label study is being conducted to evaluate the efficacy and safety of stent placement in improving the outcome of EN of insulinomas in proximity to the main pancreatic duct. METHODS AND ANALYSIS: This is a prospective, randomised, open-label, superiority clinical trial conducted at multiple tertiary centres in China. The major eligibility criterion is the presence of insulinoma located in the head and neck of the pancreas in proximity (≤2 mm) to the main pancreatic duct. Blocked randomisation will be performed to allocate patients into the stent EN group and the direct EN group. Patients in the stent EN group will go through stent placement by the endoscopist within 24 hours before the EN surgery, whereas other patients will receive EN surgery directly. The primary outcome is the assessment of the superiority of stent placement in reducing POPF rate measured by the International Study Group of Pancreatic Surgery standard. Both interventions will be performed in an inpatient setting and regular follow-up will be performed. The primary outcome (POPF rate) will be tested for superiority with the Χ2 test. The difference in secondary outcomes between the two groups will be analysed using appropriate tests. ETHICS AND DISSEMINATION: The study has been approved by the Peking Union Medical College Hospital Institutional Review Board (K23C0195), Ruijin Hospital Ethics Committee (2023-314), Peking University First Hospital Ethics Committee (2024033-001), Institutional Review Board of Xuanwu Hospital of Capital Medical University (2023223-002), Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University (XJTU1AF2023LSK-473), Institutional Review Board of Tongji Medical College Tongji Hospital (TJ-IRB202402059), Ethics Committee of Tongji Medical College Union Hospital (2023-0929) and Shanghai Cancer Center Institutional Review Board (2309282-16). The results of the study will be published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05523778.

Deubiquitylase USP31 Induces Autophagy and Promotes the Progression in Lung Squamous Cell Carcinoma Cells by Stabilizing E2F1 Expression.

BACKGROUND: Autophagy exerts a vital role in the progression of lung squamous cell carcinoma (LUSC). Ubiquitin-specific peptidase 31 (USP31) has recently been found to be involved in the development of a variety of cancers. However, whether USP31 modulates autophagy in LUSC remains unclear. METHODS: This study revealed that high levels of USP31 were discovered in LUSC tissue samples employing the Gene Expression Profiling Interactive Analysis (GEPIA) database, quantitative real- time PCR (qRT-PCR), and Western blot analysis. Cell proliferation was tested via cell counting kit 8 (CCK-8) as well as colony formation, demonstrating that USP31-stable knockdown reduced cell viability. RESULTS: Immunofluorescence analysis illustrated that USP31 knockdown blocked the occurrence of LUSC autophagy. Meanwhile, USP31 has been shown to stabilize the expression of E2F transcription factor 1 (E2F1) through the proteasome pathway. Furthermore, overexpressed E2F1 effectively eliminated the effect of USP31 knockdown on LUSC cell proliferation and autophagy. CONCLUSION: In summary, this investigation proved that USP31 promoted LUSC cell growth and autophagy, at least in part by stabilizing E2F1 expression, which provided a potential therapeutic gene for the treatment of LUSC.

Hydrolase mimic via second coordination sphere engineering in metal-organic frameworks for environmental remediation.

Enzymes achieve high catalytic activity with their elaborate arrangements of amino acid residues in confined optimized spaces. Nevertheless, when exposed to complicated environmental implementation scenarios, including high acidity, organic solvent and high ionic strength, enzymes exhibit low operational stability and poor activity. Here, we report a metal-organic frameworks (MOFs)-based artificial enzyme system via second coordination sphere engineering to achieve high hydrolytic activity under mild conditions. Experiments and theoretical calculations reveal that amide cleavage catalyzed by MOFs follows two distinct catalytic mechanisms, Lewis acid- and hydrogen bonding-mediated hydrolytic processes. The hydrogen bond formed in the secondary coordination sphere exhibits 11-fold higher hydrolytic activity than the Lewis acidic zinc ions. The MOFs exhibit satisfactory degradation performance of toxins and high stability under extreme working conditions, including complicated fermentation broth and high ethanol environments, and display broad substrate specificity. These findings hold great promise for designing artificial enzymes for environmental remediation.

Lactiplantibacillus plantarum enables blood urate control in mice through degradation of nucleosides in gastrointestinal tract.

BACKGROUND: Lactobacillus species in gut microbiota shows great promise in alleviation of metabolic diseases. However, little is known about the molecular mechanism of how Lactobacillus interacts with metabolites in circulation. Here, using high nucleoside intake to induce hyperuricemia in mice, we investigated the improvement in systemic urate metabolism by oral administration of L. plantarum via different host pathways. RESULTS: Gene expression analysis demonstrated that L. plantarum inhibited the activity of xanthine oxidase and purine nucleoside phosphorylase in liver to suppress urate synthesis. The gut microbiota composition did not dramatically change by oral administration of L. plantarum over 14 days, indicated by no significant difference in α and ß diversities. However, multi-omic network analysis revealed that increase of L. plantarum and decrease of L. johnsonii contributed to a decrease in serum urate levels. Besides, genomic analysis and recombinant protein expression showed that three ribonucleoside hydrolases, RihA-C, in L. plantarum rapidly and cooperatively catalyzed the hydrolysis of nucleosides into nucleobases. Furthermore, the absorption of nucleobase by intestinal epithelial cells was less than that of nucleoside, which resulted in a reduction of urate generation, evidenced by the phenomenon that mice fed with nucleobase diet generated less serum urate than those fed with nucleoside diet over a period of 9-day gavage. CONCLUSION: Collectively, our work provides substantial evidence identifying the specific role of L. plantarum in improvement of urate circulation. We highlight the importance of the enzymes RihA-C existing in L. plantarum for the urate metabolism in hyperuricemia mice induced by a high-nucleoside diet. Although the direct connection between nucleobase transport and host urate levels has not been identified, the lack of nucleobase transporter in intestinal epithelial cells might be important to decrease its absorption and metabolization for urate production, leading to the decrease of serum urate in host. These findings provide important insights into urate metabolism regulation. Video Abstract.

Influencing factors of self-disclosure and its impact on quality of life in patients with systemic lupus erythematosus.

BACKGROUND: Self-disclosure may enhance positive illness perceptions, whereas patients with systemic lupus erythematosus (SLE) always facing negative illness perceptions due to multiple reasons, so elucidation of factors affecting self-disclosure may facilitate the development of quality of life. METHODS: A total of 161 hospitalized patients with SLE were recruited. Scales on demographic and clinical characteristics, self-disclosure, psychosocial status (e.g. Social Support Rating Scale - SSRS) and quality of life were used to collect related information from clients. Univariate analysis was performed by Kruskal-Wallis rank-sum test or chi-square test, and multivariate analysis by ordinal logistic regression. RESULTS: Social support, drinking, depression and cause of hospitalization were found to be influencing factors of self-disclosure. Multiple logistic regression analyses revealed that the significant and independent factors associated with self-disclosure in patients with SLE were social support, drinking and depression. Domains of LupusQoL, except physical health and fatigue, were positively correlated with self-disclosure. CONCLUSIONS: With the increase of social support, the level of self-disclosure become worse, drinking, depression and cause of hospitalization are risk factors for it. Moreover, the level of self-disclosure is positively related to the LupusQoL. Medical staff should formulate effective measures according to the results to improve self-disclosure in patients with SLE and promote their quality of life.

The learning curve for robot-assisted distal pancreatectomy: a single-center experience of 301 cases.

Robotic distal pancreatectomy (RDP) has become a routine procedure in many pancreatic centers. This study aimed to describe a single-center experience with RDP since the first case, identify the learning curves of operation time and complication rate, and discuss the safety and feasibility of RDP. Methods: We collected and retrospectively analyzed the single-center surgical experience of 301 patients undergoing RDP at Peking Union Medical College Hospital (PUMCH) between 2012 and 2022 and described the change in operation proficiency and occurrence of perioperative complications in this observational study. The learning curve was assessed using the cumulative sum method. Results: We observed a three-phase pattern of RDP learning with operation time, complications, and postoperative pancreatic fistula as indicators and a two-phase pattern for spleening-preserving success. The mean operation time was 3.9 hours. The incidence rate of clinically significant postoperative pancreatic fistula (CRPOPF) was 17.9% and overall Clavien-Dindo complication rate (≥3) was 16.6%. The change of postoperative complicate rate was correlated with percentage of malignant cases. Conclusion: In the last decade, an evident decrease was seen in operation time, complication rate, and an increase in the spleen-preserving rate of distal pancreatectomy. With proper training, RDP is a safe and feasible procedure.

The impact of distress disclosure and anxiety on the association between social support and quality of life among Chinese women with systemic lupus erythematosus.

The evidence on the relationship between social support and quality of life in female systemic lupus erythematosus (SLE) patients is complex. The purpose of this study was to explore the impacts of distress disclosure and anxiety on the association between social support and quality of life among Chinese women with SLE. A cross-sectional study was conducted, and 237 samples were obtained. Measures included demographic characteristics, Lupus Quality of Life (LupusQoL), social support rate scale (SSRS), distress disclosure index (DDI), and self-rating anxiety scale (SAS). Descriptive statistics, correlation analysis, and moderated mediating effect analysis were carried out. The LupusQoL was negatively correlated with age, systemic lupus erythematosus disease activity index (SLEDAI), DDI, and SAS. SSRS had a positive predictive effect on the LupusQoL, while SLEDAI and DDI had the opposite effect. SAS had a negative predictive effect on the LupusQoL. There were interactive effects of SAS and DDI on LupusQoL. In the moderated mediation model, SAS played moderating effect in the role of DDI on LupusQoL; the DDI of female patients with SLE played a partial mediator role, the mediation effect was 0.19, and the mediation effect ratio was 33.3%. In conclusion, to pay attention to the QOL, we should consider the mediator role of distress disclosure and the moderating role of anxiety.

Causal Relationship Between Sleep Traits and Risk of Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization Study.

A correlation between sleep and systemic lupus erythematosus (SLE) has been observed in a number of prior investigations. However, little is known regarding the potential causative relationship between them. In this study, we selected genetic instruments for sleep traits from pooled data from published genome-wide association studies (GWAS). Independent genetic variants associated with six sleep-related traits (chronotype, sleep duration, short sleep duration, long sleep duration, insomnia, and daytime sleepiness) were selected as instrumental variables. A two-sample Mendelian randomization (TSMR) study was first conducted to assess the causal relationship between sleep traits and SLE (7219 cases versus 15,991 controls). The reverse MR analysis was then used to infer the causal relationship between SLE and sleep traits. Inverse variance weighted (IVW), MR Egger, Weighted median, and Weighted mode were applied to perform the primary MR analysis. MR Egger regression and the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test were used to detect horizontal pleiotropy, and Cochran's Q was used to detect heterogeneity. In studies of the effect of sleep traits on SLE risk, the IVW method demonstrated no causal relationship between chronotype, sleep duration, short sleep duration, long sleep duration, insomnia, daytime sleepiness and SLE risk. The remaining three methods agreed with the results of IVW. In studies of the effect of SLE on the risk of sleep traits, neither IVW, MR Egger, Weighted median, nor Weighted mode methods provided evidence of a causal relationship between SLE and the risk of sleep traits. Overall, our study found no evidence of a bidirectional causal relationship between genetically predicted sleep traits and SLE.

Association Between Sleep Traits and Rheumatoid Arthritis: A Mendelian Randomization Study.

Currently, the causal association between sleep disorders and rheumatoid arthritis (RA) has been poorly understood. In this two-sample Mendelian randomization (TSMR) study, we tried to explore whether sleep disorders are causally associated with RA. Seven sleep-related traits were chosen from the published Genome-Wide Association Study (GWAS): short sleep duration, frequent insomnia, any insomnia, sleep duration, getting up, morningness (early-to-bed/up habit), and snoring, 27, 53, 57, 57, 70, 274, and 42 individual single-nucleotide polymorphisms (SNPs) (P < 5 × 10-8) were obtained as instrumental variables (IVs) for these sleep-related traits. Outcome variables were obtained from a public GWAS study that included 14,361 cases and 43,923 European Ancestry controls. The causal relationship between sleep disturbances and RA risk were evaluated by a two-sample Mendelian randomization (MR) analysis using inverse variance weighted (IVW), MR-Egger regression, weighted median, and weight mode methods. MR-Egger Regression and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) were used to test for horizontal pleomorphism and outliers. There was no evidence of a link between RA and frequent insomnia (IVW, odds ratio (OR): 0.99; 95% interval (CI): 0.84-1.16; P = 0.858), any insomnia (IVW, OR: 1.09; 95% CI: 0.85-1.42; P = 0.489), sleep duration (IVW, OR: 0.65, 95% CI: 0.38-1.10, P = 0.269), getting up (IVW, OR: 0.56, 95% CI: 0.13-2.46, P = 0.442), morningness (IVW, OR: 2.59; 95% CI: 0.73-9.16; P = 0.142), or snoring (IVW, OR: 0.95; 95% CI: 0.68-1.33; P = 0.757). Short sleep duration (6h) had a causal effect on RA, as supported by IVW and weighted median (OR: 1.47, 95% CI: 1.12-1.94, P = 0.006; OR: 1.43, 95%CI:1.01-2.05, P = 0.047). Sensitivity analysis showed that the results were stable. Our findings imply that short sleep duration is causally linked to an increased risk of RA. Therefore, sleep length should be considered in disease models, and physicians should advise people to avoid short sleep duration practices to lower the risk of RA.

Reliability and validity of the Chinese version of the eight-item Morisky Medication Adherence Scale in Chinese patients with systemic lupus erythematosus.

OBJECTIVE: To evaluate the reliability and validity of the Chinese version of the eight-item Morisky Medication Adherence Scale (MMAS-8) in Chinese patients with systemic lupus erythematosus (SLE). METHODS: The survey was conducted with a consecutive sampling of 158 Chinese SLE patients attending public hospitals from January to March 2021. We used the translated Chinese version of the MMAS-8 to collect related data. Reliability, item, and factor analyses were used to test the reliability and validity of the MMAS-8 scale in the selected patients. The internal consistency reliability was evaluated using Cronbach's α coefficient. Test-retest reliability was assessed using intraclass correlation coefficients (ICCs) in a subset of 30 participants. Construct validity was evaluated using confirmatory factor analysis and correlations between the Self-efficacy for Appropriate Medication Use Scale (SEAMS) and related measures. RESULTS: The internal consistency reliability of the Chinese version of the MMAS-8 was high (Cronbach's α = 0.817), and the test-retest reliability was excellent (intraclass correlation = 0.947; P < 0.001). There were significant differences in the F test and t test between the two extreme groups before and after the ranking of 27% of the questionnaire scores (P < 0.001). The Kaiser-Meyer-Olkin (KMO) value of construct validity was 0.860. The spherical test value of Bartlettgers was 417.8822. Factor analysis yielded three components that accounted for 69.375% of the total variance. Exploratory factor analysis identified three dimensions of the Chinese version of the MMAS-8. In terms of criterion validity, the correlation of the MMAS-8 score in SEAMS indicated that the convergent validity was good (r = 0.926; P < 0.001). CONCLUSIONS: This study shows that the Chinese version of the Medication Adherence Scale-8 is a reliable and valid tool for assessing medication adherence in Chinese SLE patients. Key Points • Many factors affect medication adherence in SLE patients. • Many questionnaires measure medication adherence levels. • There is a lack of reliable validation of medication adherence questionnaires specifically for SLE patients.

Identification and in silico Analysis of Nonsense SNPs of Human Colorectal Cancer Protein.

Colorectal cancer (CRC) is the third most prevalent disease in the world, with an estimated 1.2 million new cases each year. Spontaneous CRCs account for around 70% of all CRCs, are caused by somatic mutations. Minor variations or single-nucleotide polymorphisms (SNPs) in oncogene or tumor-suppressor genes cause familial CRC. MSH2 and MSH6 genes are located on chromosome 2. These genes products are involved in the repair of DNA replication defects. If these proteins are changed, the replication errors are not rectified, resulting in damaged DNA leading to colorectal cancer. We employed a variety of computational methodologies to find nsSNPs that are harmful to the structure and function of the MSH6 protein and could be causing CRC in our study. SIFT, PROVEAN, Poly- Phen-2, PhD-SNP, and SNPs&GO were among the in silico methods used to do the computational research. According to the findings, mutations of G932Q, E1234Q, and F1104Q are important alterations in native MSH6 protein rs35717727 that may contribute to its dysfunction and, ultimately, disease. The study also provided three-dimensional structures of the native MSH6 protein and mutations. These nsSNPs should be considered as key target mutations in many disorders involving MSH6 dysfunction in future studies. This is the first thorough study to use in silico technologies to assess MSH6 gene variants, and it will be extremely useful in planning largescale investigations and developing precision medicines to treat disorders caused by these polymorphisms. Additionally, animal models of various autoimmune disorders with these mutations could aid in determining their precise involvement.

Frailty in rheumatoid arthritis: A systematic review and meta-analysis.

OBJECTIVE: Rheumatoid arthritis (RA) may cause damage to multiple organs and may further restrict the patient's physical, psychological and social functions. This meta-analysis aimed to explore the prevalence of frailty and prefrailty and the influential factors in RA patients. METHODS: PubMed, Web of Science, Cochrane, Embase, and CNKI were searched to identify related articles. Articles published before July 23rd, 2021 that assessed frailty in patients with RA qualified for the systematic review and meta-analysis. A quality appraisal of the studies was performed using the Agency for Healthcare Research and Quality and Newcastle-Ottawa Scales. The pooled results were displayed as odds ratios or standardized mean differences (ORs/SMDs) and 95% confidence intervals (CIs). RESULTS: The article search generated 2273 articles, of which 16 satisfied the inclusion criteria and were merged in the final review. A total of 8556 RA patients were finally included. The pooled prevalence of frailty in the patients with RA was 33.5% (95% CI: 25.2-41.7%), and the pooled prevalence of prefrailty was 39.9% (95% CI: 29.4-50.3%). Subgroup analyses showed that frailty was more prevalent in females (24.7%) than in males (19.1%). The prevalence of prefrailty in females was similar to that in males among the RA patients. Frailty in RA was associated with the female sex (OR: 1.47, 95% CI: 1.04-2.07) and disease activity (OR: 1.47, 95% CI: 1.03-2.09). CONCLUSION: Frailty is prevalent in RA patients. Female gender and disease activity are associated with the prevalence of frailty in RA patients.

Risk factors and prevention of postoperative pancreatic fistula after insulinoma enucleation:a retrospective study from a high-volume center.

BACKGROUND/OBJECTIVES: Enucleation is an effective surgical method to treat pancreatic insulinoma, however, the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) is high. We aim to investigate the risk factors for CR-POPF which have not been well characterized and develop effective methods to prevent CR-POPF after enucleation. METHODS: This retrospective cohort study included 161 patients diagnosed with insulinoma from June 2016 to July 2020 in Peking Union Medical College Hospital. The risk factors for CR-POPF were evaluated and the role of prophylactic pre-operative pancreatic stent to prevent the occurrence of CR-POPF after enucleation of pancreatic insulinoma were explored. RESULTS: A cohort of 161 insulinoma cases were reviewed. The CT or MRI imaging reports could be tracked in 108 cases. A total of 96 patients underwent surgery, while 81 experienced pancreatic enucleation. Univariate and multivariate analyses showed that the distance from insulinoma to the main pancreatic duct (MPD) ≤2 mm was an independent risk factor for CR-POPF (p = 0.003, OR = 6.011, 95% Cl 1.852-19.512). The pre-operative pancreatic stent substantially reduced the incidence of CR-POPF in patients with tumor located in proximity to (distance ≤2 mm) the MPD (CR-POPF of the stented group vs the non-stented group: 37.5% vs 71.4%, p = 0.028). CONCLUSIONS: The distance from insulinoma to MPD ≤2 mm is a predictive factor for CR-POPF after enucleation. Pancreatic duct stenting may benefit patients with insulinoma in proximity to the MPD by enabling a lower CR-POPF rate, so it should be considered before the enucleation of the insulinoma in proximity to the MPD (distance ≤2 mm).

Psychological Status and Correlated Factors of Primary Medical Staff During the COVID-19 Outbreak in Hefei City, China.

OBJECTIVE: To investigate the mental illness and correlated factors of primary medical staff during the COVID-19 outbreak in Hefei city, China. METHODS: A total of 180 primary medical staff were randomly selected from seven community hospitals in Hefei Economic and Technological Development Zone as a study group. One hundred and eighty-two health people were recruited as the control group. The self-rating Anxiety Scale (SAS), self-rating Depression Scale (SDS) and Psychological questionnaire of public health emergencies were distributed to them for evaluation. RESULTS: The score of SAS, SDS in study group was higher than that in control group [(35.57±10.39) vs (31.31±7.98); (44.16±8.46) vs (41.47±9.47)] (t=4.371, P< 0.001; t=2.849, P=0.005). The fear subscale and total score in the psychological questionnaire of sudden public health events were negatively correlated with age (r=-0.216, P=0.004; r=-0.154, P=0.039). Marriage was negatively correlated with depression subscales in psychological questionnaires of SAS, SDS and sudden public health events (r=-0.184, P=0.013; r=-0.298, P<0.001; r=-0.161, P=0.031; r=-0.147, P=0.049). Education level was positively correlated with the total score of a psychological questionnaire for sudden public health events (r=0.151, P=0.043); Logistic regression analysis showed that marital status was a protective factor of psychological abnormality. CONCLUSION: It is necessary to pay attention to the psychological status of primary medical staff, especially the young unmarried medical staff.

Biosynthesis of 3-Hydroxy-3-Methylbutyrate from l-Leucine by Whole-Cell Catalysis.

3-Hydroxy-3-methylbutyrate (HMB) is an important compound that can be used for the synthesis of a variety of chemicals in the food and pharmaceutical fields. Here, a biocatalytic method using l-leucine as a substrate was designed and constructed by expressing l-amino acid deaminase (l-AAD) and 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) in Escherichia coli. To reduce the influence of the rate-limiting step on the cascade reaction, two 4-HPPD mutants were screened by rational design and both showed improved catalytic activity. Under optimal reaction conditions, the maximum conversion rate and production rate were 80% and 0.257 g/L·h, respectively. HMB production could be realized with high efficiency without an additional supply of adenosine triphosphate (ATP), which successfully overcomes the shortcomings of chemical production and fermentation methods. This design-based strategy of constructing a whole-cell catalyst system from l-leucine might serve as an alternative route to HMB synthesis.

Physical Stability of Medium-Chain Triglyceride/Long-Chain Triglyceride Emulsion Injections From 5 Manufacturers in High-Concentration Electrolyte-Based Total Nutrient Admixtures.

BACKGROUND: Lipid emulsion injections for parenteral nutrition are an important source of energy and essential fatty acids. Yet stability and compounding challenges remain. We compared the physicochemical stability of 5 commercial medium-chain triglyceride/long-chain triglyceride (MCT/LCT)-based lipid emulsions compounded in total nutrient admixtures (TNAs). METHODS: Stability of the MCT/LCT-based TNAs was assessed when compounded with high concentrations of electrolytes. We measured mean droplet diameter (MDD), percentage of fat residing in globules ≥5 µm (PFAT5), pH, and osmolality immediately after compounding (time 0) and 6, 12, 18, 24, 36, 48, 60, and 72 hours later. Repeated-measures analyses of variance were used to evaluate changes in stability over time, and post hoc tests were used to assess group differences. RESULTS: Over 72 hours, MDD of TNAs ranged from 0.206 to 0.713 µm, PFAT5 from 0.58% × 10-3 to 43.18% × 10-3 , pH from 5.769 to 5.879, and osmolality from 1304 to 1357 mOsm/kg. MDDs and PFAT5s showed a tendency to increase gradually over the first 24 hours and then decrease or remained stable after that. We identified some significant differences in MDDs and PFAT5s among the 5 MCT/LCT-based TNAs, although all met the United States Pharmacopeia <729> standards. CONCLUSIONS: The stability of some commercial MCT/LCT-based TNAs under high concentrations of electrolytes exhibits differences over the 72 hours after compounding. Clinicians should pay attention, therefore, to possible performance differences of injectable lipid emulsions produced by different manufacturers when compounded in TNAs under high electrolyte concentrations.

MARCKSL1 promotes the proliferation, migration and invasion of lung adenocarcinoma cells.

Lung cancer is the most common cancer in males and females and ~40% of lung cancer cases are adenocarcinomas. Previous studies have demonstrated that myristoylated alanine rich protein kinase C substrate (MARCKS) is upregulated in several types of cancer and is associated with poor prognosis in patients with breast cancer. However, its expression level and role in lung adenocarcinoma remain unknown. Therefore, the aim of the present study was to investigate the expression level and biological functions of MARCKS like 1 (MARCKSL1), a member of the MARCKS family, in lung adenocarcinoma. The expression level of MARCKSL1 was examined in human lung adenocarcinoma tissues and cell lines. MARCKSL1-specific small interfering RNAs effectively suppressed its expression level and significantly inhibited the proliferation, migration and invasion of lung adenocarcinoma cells. Additionally, the role of MARCKSLI in the regulation of metastasis was examined. Silencing MARCKSL1 decreased the expression of the epithelial-mesenchymal transition (EMT)-associated proteins E-cadherin, N-cadherin, vimentin and snail family transcriptional repressor 2, and decreased the phosphorylation level of AKT. The results obtained in the current study suggested that MARCKSL1 promoted the progression of lung adenocarcinoma by regulating EMT. MARCKSLI may have prognostic value and serve as a novel therapeutic target in lung adenocarcinoma.

Discovery and validation of potential bacterial biomarkers for lung cancer.

Microbes are residents in a number of body sites, including the oral and nasal cavities, which are connected to the lung via the pharynx. The associations between oral diseases and increased risk of lung cancer have been reported in previous prospective studies. In this study, we measured variations of salivary microbiota and evaluated their potential association with lung cancer, including squamous cell carcinoma (SCC) and adenocarcinoma (AC). A three-phase study was performed: First, we investigated the salivary microbiota from 20 lung cancer patients (10 SCC and 10 AC) and control subjects (n=10) using a deep sequencing analysis. Salivary Capnocytophaga, Selenomonas, Veillonella and Neisseria were found to be significantly altered in patients with SCC and AC when compared to that in control subjects. Second, we confirmed the significant changes of Capnocytophaga, Veillonella and Neisseria in the same lung cancer patients using quantitative PCR (qPCR). Finally, these bacterial species were further validated on new patient/control cohorts (n=56) with qPCR. The combination of two bacterial biomarkers, Capnocytophaga and Veillonella, yielded a receiver operating characteristic (ROC) value of 0.86 with an 84.6% sensitivity and 86.7% specificity in distinguishing patients with SCC from control subjects and a ROC value of 0.80 with a 78.6% sensitivity and 80.0% specificity in distinguishing patients with AC from control subjects. In conclusion, we have for the first time demonstrated the association of saliva microbiota with lung cancer. Particularly, the combination of the 16S sequencing discovery with qPCR validation studies revealed that the levels of Capnocytophaga and Veillonella were significantly higher in the saliva from lung cancer patients, which may serve as potential biomarkers for the disease detection/classification.

Subtype identification in acutely dissociated rat nodose ganglion neurons based on morphologic parameters.

Nodose ganglia are composed of A-, Ah- and C-type neurons. Despite their important roles in regulating visceral afferent function, including cardiovascular, pulmonary, and gastrointestinal homeostasis, information about subtype-specific expression, molecular identity, and function of individual ion transporting proteins is scarce. Although experiments utilizing the sliced ganglion preparation have provided valuable insights into the electrophysiological properties of nodose ganglion neuron subtypes, detailed characterization of their electrical phenotypes will require measurements in isolated cells. One major unresolved problem, however, is the difficulty to unambiguously identify the subtype of isolated nodose ganglion neurons without current-clamp recording, because the magnitude of conduction velocity in the corresponding afferent fiber, a reliable marker to discriminate subtypes in situ, can no longer be determined. Here, we present data supporting the notion that application of an algorithm regarding to microscopic structural characteristics, such as neuron shape evaluated by the ratio between shortest and longest axis, neuron surface characteristics, like membrane roughness, and axon attachment, enables specific and sensitive subtype identification of acutely dissociated rat nodose ganglion neurons, by which the accuracy of identification is further validated by electrophysiological markers and overall positive predictive rates is 89.26% (90.04%, 76.47%, and 98.21% for A-, Ah, and C-type, respectively). This approach should aid in gaining insight into the molecular correlates underlying phenotypic heterogeneity of nodose ganglia. Additionally, several critical points that help for neuron identification and afferent conduction calibration are also discussed.