Development of a diagnostic algorithm to ascertain malignant pleural effusion utilizing clinical indicators and serum metal concentrations.

Background: Malignant pleural effusion (MPE) is prevalent among cancer patients, indicating pleural metastasis and predicting poor prognosis. However, accurately identifying MPE in clinical settings is challenging. The aim of this study was to establish an innovative nomogram-derived model based on clinical indicators and serum metal ion levels to identify MPE. Methods: From July 2020 to May 2022, 428 patients diagnosed with pleural effusion (PE) were consecutively recruited. Comprehensive demographic details, clinical symptoms, imaging data, pathological information, and laboratory results, including serum metal ion levels, were systematically collected. The nomogram was created by incorporating the most significant predictors identified through LASSO and multivariate logistic regression analysis. The predictors were assigned weighted points based on their respective regression coefficients, allowing for the calculation of a total score that corresponds to the probability of MPE. Internal validation using bootstrapping techniques assessed the nomogram's performance, including calibration, discrimination, and clinical applicability. Results: Seven key variables were identified using LASSO regression and multiple regression analysis, including dyspnea, fever, X-ray/CT compatible with malignancy, pleural carcinoembryonic antigen(pCEA), serum neuron-specific enolase(sNSE), serum carcinoembryonic antigen(sCEA), and pleural lactate dehydrogenase(pLDH). Internal validation underscored the superior performance of our model (AUC=0.940). Decision curve analysis (DCA) analysis demonstrated substantial net benefit across a probability threshold range > 1%. Additionally, serum calcium and copper levels were significantly higher, while serum zinc levels were significantly lower in MPE patients compared to benign pleural effusion (BPE) patients. Conclusion: This study effectively developed a user-friendly and reliable MPE identification model incorporating seven markers, aiding in the classification of PE subtypes in clinical settings. Furthermore, our study highlights the clinical value of serum metal ions in distinguishing malignant pleural effusion from BPE. This significant advancement provides essential tools for physicians to accurately diagnose and treat patients with MPE.

Machine learning-enhanced insights into sphingolipid-based prognostication: revealing the immunological landscape and predictive proficiency for immunomotherapy and chemotherapy responses in pancreatic carcinoma.

Background: With a poor prognosis for affected individuals, pancreatic adenocarcinoma (PAAD) is known as a complicated and diverse illness. Immunocytes have become essential elements in the development of PAAD. Notably, sphingolipid metabolism has a dual function in the development of tumors and the invasion of the immune system. Despite these implications, research on the predictive ability of sphingolipid variables for PAAD prognosis is strikingly lacking, and it is yet unclear how they can affect PAAD immunotherapy and targeted pharmacotherapy. Methods: The investigation process included SPG detection while also being pertinent to the prognosis for PAAD. Both the analytical capability of CIBERSORT and the prognostic capability of the pRRophetic R package were used to evaluate the immunological environments of the various HCC subtypes. In addition, CCK-8 experiments on PAAD cell lines were carried out to confirm the accuracy of drug sensitivity estimates. The results of these trials, which also evaluated cell survival and migratory patterns, confirmed the usefulness of sphingolipid-associated genes (SPGs). Results: As a result of this thorough investigation, 32 SPGs were identified, each of which had a measurable influence on the dynamics of overall survival. This collection of genes served as the conceptual framework for the development of a prognostic model, which was carefully assembled from 10 chosen genes. It should be noted that this grouping of patients into cohorts with high and low risk was a sign of different immune profiles and therapy responses. The increased abundance of SPGs was identified as a possible sign of inadequate responses to immune-based treatment approaches. The careful CCK-8 testing carried out on PAAD cell lines was of the highest importance for providing clear confirmation of drug sensitivity estimates. Conclusion: The significance of Sphingolipid metabolism in the complex web of PAAD development is brought home by this study. The novel risk model, built on the complexity of sphingolipid-associated genes, advances our understanding of PAAD and offers doctors a powerful tool for developing personalised treatment plans that are specifically suited to the unique characteristics of each patient.

m6A eraser FTO impairs gemcitabine resistance in pancreatic cancer through influencing NEDD4 mRNA stability by regulating the PTEN/PI3K/AKT pathway.

BACKGROUND: Gemcitabine resistance has brought great challenges to the treatment of pancreatic cancer. The N6-methyladenosine (m6A) mutation has been shown to have a significant regulatory role in chemosensitivity; however, it is not apparent whether gemcitabine resistance can be regulated by fat mass and obesity-associated protein (FTO). METHODS: Cells with established gemcitabine resistance and tissues from pancreatic cancer patients were used to evaluate FTO expression. The biological mechanisms of the effects of FTO on gemcitabine resistant cells were investigated using CCK-8, colony formation assay, flow cytometry, and inhibitory concentration 50. Immunoprecipitation/mass spectrometry, MeRIP-seq, RNA sequencing and RIP assays, RNA stability, luciferase reporter, and RNA pull down assays were employed to examine the mechanism of FTO affecting gemcitabine resistant pancreatic cancer cells. RESULTS: The results revealed that FTO was substantially expressed in cells and tissues that were resistant to gemcitabine. Functionally, the gemcitabine resistance of pancreatic cancer could be enhanced by FTO, while its depletion inhibited the growth of gemcitabine resistant tumor cells in vivo. Immunoprecipitation/mass spectrometry showed that the FTO protein can be bound to USP7 and deubiquitinated by USP7, leading to the upregulation of FTO. At the same time, FTO knockdown significantly decreased the expression level of NEDD4 in an m6A-dependent manner. RNA pull down and RNA immunoprecipitation verified YTHDF2 as the reader of NEDD4, which promoted the chemoresistance of gemcitabine resistant cells. FTO knockdown markedly increased the PTEN expression level in an NEDD4-dependent manner and influenced the chemosensitivity to gemcitabine through the PI3K/AKT pathway in pancreatic cancer cells. CONCLUSION: In conclusion, we found that gemcitabine resistance in pancreatic cancer can be influenced by FTO that demethylates NEDD4 RNA in a m6A-dependent manner, which then influences the PTEN expression level and thereby affects the PI3K/AKT pathway. We also identified that the FTO level can be upregulated by USP7.

Analysis of Voluntary Environmental Behavior and Innovation Quality of Chinese Textile Enterprises Based on Grounded Theory and Propensity Score Matching.

At a new stage of "carbon peak" and "carbon neutral," we need to strengthen the internal impetus of institutions and policies to promote ecological civilization construction. The initiative implementation of voluntary environmental behavior (VEB) is an effective way for enterprises to achieve high quality sustainable development. The VEB of enterprises include but are not limited to compliance with voluntary environmental regulations (VER). Different from the existing literature on enterprise VER, most of which are just the verification of ISO14001, the study conducts a comprehensive exploratory research on the theoretical framework of what is driving the VEB of Chinese textile enterprises. First, based on grounded theory, the paper coded the hand-collected environmental text information of Chinese listed textile enterprises from 2004 to 2018 and constructed a complete theoretical analysis framework from motivation to performance evaluation of enterprise VEB. Second, PSM method is taken to verify the conceptual model. As a result, we find the following: (1) in addition to ISO14001, the textile enterprises involve many industry-specific VER. (2) The VEB and VER of Chinese textile enterprises promote each other. (3) Either following VER or implementing VEB can effectively increase the innovation input and then actively improve the innovation quality of Chinese textile enterprises. In this way, the conclusion not only provides analysis ideas for future empirical research, but also offers practical suggestions to Chinese textile enterprises and policy makers for environmental management.

Repeated remote ischaemic preconditioning can prevent acute mountain sickness after rapid ascent to a high altitude.

BACKGROUND: This study assessed the effectiveness of 4 different repeated remote ischaemic preconditioning (RIPC) protocols varying in duration and frequency for preventing acute mountain sickness (AMS) after rapid ascent to high altitude. METHODS: In a randomized but not blinded design, participants were assigned to receive either of the four RIPC treatments at low altitude (Group A, once daily for 1 week; Group B, twice daily for 1 week; Group C, once daily for 4 weeks; and Group D, twice daily for 4 weeks) or control (no specific sham treatment). Participants were then flown to a high altitude (3650 m). The primary outcome was the incidence and severity of AMS evaluated by the Lake Louise score (LLS) after arrival; vital signs were collected simultaneously. RESULTS: A total of 250 participants (50 per group; mean age 38.56 ± 0.76 years) were included. The overall AMS incidence was 26.4%. A total of 20 AMS cases (40%) occurred in the control group, 15 cases (30%) both in the RIPC A and RIPC B groups (RR 1.3; 95%CI 0.8-2.3; χ2 = 1.099; p = 0.29), and 8 cases (16%) both in the RIPC C and D groups (RR 2.5; 95%CI 1.2 - 5.2; χ2 = 7.143, p < 0.01), with significantly lower LLSs in the RIPC C and D groups (F = 6.51, p < 0.001). The scores of gastrointestinal symptoms (F = 7.42, p < 0.001) and dizziness (F = 9.82, p < 0.001) but not headache (F = 0.60, p > 0.05) were lower in the RIPC groups compared to control. The blood oxygen saturation level (SpO2) decreased less in the RIPC B, C and D groups compared to control after arrival at a high altitude (F = 11.42, p < 0.001). The number of RIPC treatments received was moderately correlated with SpO2 (R = 0.38, p < 0.001), and SpO2 was moderately inversely correlated with the LLS (R = -0.48, p < 0.001). CONCLUSION: This study demonstrated that a four-week RIPC intervention but not a one-week regimen reduced AMS incidence and severity; however, a placebo effect might have contributed to these results.

Risk factors and prediction nomogram model for psychosocial and behavioural problems among children and adolescents during the COVID-19 pandemic: A national multicentre study: Risk Factors of Childhood Psychosocial Problems.

BACKGROUND: We aimed to explore the risk profiles attributable to psychosocial and behavioural problems during the coronavirus disease 2019 pandemic. To this end, we created a risk-prediction nomogram model. METHODS: A national multicentre study was conducted through an online questionnaire involving 12,186 children (6-11 years old) and adolescents (12-16 years old). Respondents' psychosocial and behavioural functioning were assessed using the Achenbach Child Behaviour Checklist (CBCL). Data were analysed using STATA software and R-language. RESULTS: The positive detection rate of psychological problems within Wuhan was greater than that outside Wuhan for schizoid (P = 0.005), and depression (P = 0.030) in children, and for somatic complaints (P = 0.048), immaturity (P = 0.023), and delinquent behaviour (P = 0.046) in adolescents. After graded multivariable adjustment, seven factors associated with psychological problems in children and adolescents outside Wuhan were parent-child conflict (odds ratio (OR): 4.94, 95% confidence interval (95% CI): 4.27-5.72), sleep problems (OR: 4.05, 95% CI: 3.77-4.36), online study time (OR: 0.41, 95% CI: 0.37-0.47), physical activity time (OR: 0.510, 95% CI: 0.44-0.59), number of close friends (OR: 0.51, 95% CI: 0.44-0.6), time spent playing videogames (OR: 2.26, 95% CI: 1.90-2.69) and eating disorders (OR: 2.71, 95% CI: 2.35-3.11) (all P < 0.001). Contrastingly, within Wuhan, only the first four factors, namely, parent-child conflict (5.95, 2.82-12.57), sleep problems (4.47, 3.06-6.54), online study time (0.37, 0.22-0.64), and physical activity time (0.42, 0.22-0.80) were identified (all P < 0.01). Accordingly, nomogram models were created with significant attributes and had decent prediction performance with C-indexes over 80%. LIMITATION: A cross-sectional study and self-reported measures. CONCLUSIONS: Besides the four significant risk factors within and outside Wuhan, the three additional factors outside Wuhan deserve special attention. The prediction nomogram models constructed in this study have important clinical and public health implications for psychosocial and behavioural assessment.

Psychosocial and behavioral problems of children and adolescents in the early stage of reopening schools after the COVID-19 pandemic: a national cross-sectional study in China.

This study aims to explore the psychosocial and behavioral problems of children and adolescents in the early stage of reopening schools. In this national cross-sectional study, a total of 11072 students from China were naturally divided into two groups based on their schooling status: reopened schools (RS) and home schooling (HS) group. The psychosocial and behavioral functioning were measured by Achenbach Child Behaviour Checklist (CBCL) and compared in these two groups. Multivariable logistic regression analyses were conducted to explore the independent predictors associated with the psychosocial and behavioral problems. Our results showed that the students in the RS group had more adverse behaviors than that of HS group. The RS group had the higher rates of parent-offspring conflict, prolonged homework time, increased sedentary time and sleep problems (all p < 0.001). When separate analyses were conducted in boys and girls, the RS group had the higher scores for (1) overall behavioral problems (p = 0.02 and p = 0.01), internalizing (p = 0.02 and p = 0.02) and externalizing (p = 0.02 and p = 0.004) behaviors in the 6-11 age group; (2) externalizing (p = 0.049 and p = 0.006) behaviors in the 12-16 age group. Multivariable regression showed parent-offspring conflict and increased sedentary time were the most common risk factors, while physical activity and number of close friends were protective factors for behavior problems in RS students (p < 0.01 or 0.05). The present study revealed that students' psychosocial and behavioral problems increased in the early stage of schools reopened unexpectedly. These findings suggest that close attention must be paid and holistic strategies employed in the school reopening process of post-COVID-19 period.

Detection Method for Bolted Connection Looseness at Small Angles of Timber Structures based on Deep Learning.

Bolted connections are widely used in timber structures. Bolt looseness is one of the most important factors leading to structural failure. At present, most of the detection methods for bolt looseness do not achieve a good balance between cost and accuracy. In this paper, the detection method of small angle of bolt loosening in a timber structure is studied using deep learning and machine vision technology. Firstly, three schemes are designed, and the recognition targets are the nut's own specification number, rectangular mark, and circular mark, respectively. The Single Shot MultiBox Detector (SSD) algorithm is adopted to train the image datasets. The scheme with the smallest identification angle error is the one identifying round objects, of which the identification angle error is 0.38°. Then, the identification accuracy was further improved, and the minimum recognition angle reached 1°. Finally, the looseness in a four-bolted connection and an eight-bolted connection are tested, confirming the feasibility of this method when applied on multi-bolted connection, and realizing a low operating costing and high accuracy.

Overexpression of long noncoding RNA CUDR promotes hepatic differentiation of human umbilical cord mesenchymal stem cells.

Previous studies have shown that long noncoding RNAs (lncRNAs) are capable of regulating cell differentiation and pluripotency. The objective of the present study was to explore the effect of lncRNA cancer upregulated drug resistant (CUDR) on the hepatic differentiation of human umbilical cord mesenchymal stem cells (HuMSCs). HuMSCs were subjected to a hepatogenic differentiation protocol. The level of CUDR was monitored by reverse transcription­quantitative PCR (RT­qPCR) following certain stages of hepatic differentiation. Lentivirus transfection was used to achieve CUDR overexpression. The hepatocyte­related proteins and mRNAs were then examined by immunofluorescence, ELISA and RT­qPCR analyses. The results showed that CUDR was upregulated during the hepatic differentiation of HuMSCs. Upregulation of CUDR can improve hepatic differentiation of HuMSCs, including hepatocyte­related genes and proteins. In addition, it was also found that liver­enriched transcription factors were upregulated after CUDR overexpression. Moreover, there was an association between the Wnt/ß­catenin pathway and CUDR. In summary, these results demonstrated that the overexpression of CUDR could improve the hepatic differentiation of HuMSCs, therefore it could be an ideal source for regenerative therapy.

Clinical analysis of hepatic angioleiomyoma: Two case reports.

RATIONALE: Angioleiomyoma is an uncommon benign tumor that originates from the vascular smooth muscle cells and contains thick-walled vessels. It can appear anywhere in the body but more frequently in the extremities (especially in the lower limbs) and rarely invades the internal organs. PATIENT CONCERNS: A 52-year-old Chinese woman was referred to our hospital because of finding liver neoplasm 2 weeks ago (case first) and a 64-year-old Chinese woman was admitted to hospital with enlargement of the hepatic neoplasm revealed in follow-up, who was diagnosed with angioleiomyoma of left kidney 2 years ago (case second). DIAGNOSIS: All patients were diagnosed with hepatic angioleiomyoma by pathological results. INTERVENTIONS: All patients received surgical treatment, with laparoscopic hepatectomy of the IVb segment in case 1 and laparoscopic hepatic left lateral lobectomy in case 2. OUTCOMES: The 2 patients have eventually recovered, and no recurrences or other complications have been observed so far. LESSONS: Because of atypical clinical symptoms, no specificity in laboratory examination, and lack of characteristic imaging findings, angioleiomyoma is easily misdiagnosed for another disease of the liver. But with complete resection, the prognosis is generally good.

Bouveret's syndrome: A rare presentation of gastric outlet obstruction.

Bouveret's syndrome refers to gastric outlet obstruction caused by the formation of a cholecystoduodenal fistula with subsequent migration and impaction of a large gallstone into the duodenum. A case of a 59-year-old male who presented to our institution with consistent abdominal pain and nausea is reported herein. Bouveret's syndrome was diagnosed after conducting a computed tomography scan. Surgery was performed wherein gallstone removal was followed by cholecystectomy and fistula repair associated with a pyloric bypass via gastro-jejunostomy. The patient recovered well following surgery and has remained free of symptoms for the last year.

Differentiation of umbilical cord mesenchymal stem cells into hepatocytes in comparison with bone marrow mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are considered to be an ideal source for the cell therapy of end­stage liver diseases. Umbilical cord (UC)­MSCs can be obtained via a non­invasive procedure and can be easily cultured, making them potentially superior candidates for cell transplantation when compared with MSCs from other sources. In the present study, UC­MSCs were induced to differentiate into hepatocytes and were compared with bone marrow (BM)­MSCs for their hepatic differentiation potential. UC­MSCs showed significantly higher proliferation than BM­MSCs. Under hepatic induction, UC­MSCs and BM­MSCs could differentiate into hepatocytes. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis revealed that a higher expression of the hepatocyte­specific genes albumin, cytochrome P450 3A4 (CYP3A4), tyrosine­aminotransferase, glucose­6phosphate, α1 antitrypsin and α­fetoprotein was detected in differentiated UC­MSCs when compared with differentiated BM­MSCs. The results of ELISA and western blotting were in accordance with those of RT­qPCR. Theses results indicated that UC­MSCs had higher hepatic differentiation potential than BM­MSCs. Therefore, UC­MSCs may be advantageous over BM­MSCs for the treatment of end­stage liver disease.

Insights into enhanced visible-light photocatalytic activity of C60 modified g-C3N4 hybrids: the role of nitrogen.

Recent experiments have shown that the photocatalytic activity of g-C3N4 can be greatly enhanced by C60 modification, however, a fundamental understanding of its mechanistic operation is still lacking. Using first-principles calculations, the interfacial effects of C60/g-C3N4 nanocomposites on the electronic properties, charge transfer and optical response have been explored in detail. For different stacking patterns, the two constituents are always linked by van der Waals (vdW) forces without any exception, and form type-II heterojunctions in most cases. The valence band maximum and conduction band minimum of these heterostructures are dominated by the unsaturated nitrogen (N2) atoms and C60 molecule, respectively, which strongly interact with each other, resulting in strong charge transfer between the two involved constituents and an obvious bending of the g-C3N4 sheets. The unsaturated N2 atoms included in the interfaces have a significant influence on promoting the photocatalytic performance, while the existence of saturated nitrogen (N1 and N3) atoms lying in the interfaces will weaken the interfacial interactions between C60 molecules and the g-C3N4 monolayers. Moreover, the sensitive optical response and satisfactory type-II band alignment clearly show that the C60/g-C3N4 heterostructure is an outstanding photocatalyst for hydrogen production. We proposed a deep insight (the role of nitrogen) into understanding the improved photocatalytic ability of the C60/g-C3N4 nanocomposites, which may contribute to the rational design of both C60/g-C3N4 and g-C3N4-based nanocomposite photocatalysts.

Transplantation of insulin-producing cells to treat diabetic rats after 90% pancreatectomy.

AIM: To investigate the effects of transplantation of insulin-producing cells (IPCs) in the treatment of diabetic rats after 90% pancreatectomy. METHODS: Human umbilical cord mesenchymal stem cells (UCMSCs) were isolated and induced into IPCs using differentiation medium. Differentiated cells were examined by dithizone (DTZ) staining, reverse transcription-polymerase chain reaction (RT-PCR), and real-time RT-PCR. C-peptide release, both spontaneously and after glucose challenge, was measured by ELISA. IPCs were then transplanted into Sprague-Dawley rats after 90% pancreatectomy and blood glucose levels and body weight were measured. RESULTS: The differentiated cells were positive for DTZ staining and expressed pancreatic ß-cell related genes. C-peptide release by the differentiated cells increased after glucose challenge (380.6 ± 15.32 pmol/L vs 272.4 ± 15.32 pmol/L, P < 0.05). Further, in the cell transplantation group, blood sugar levels were significantly lower than in the sham group 2 wk after transplantation (18.7 ± 2.5 mmol/L vs 25.8 ± 1.25 mmol/L, P < 0.05). Glucose tolerance tests showed that 45 min after intraperitoneal glucose injection, blood glucose levels were significantly lower on day 56 after transplantation of IPCs (12.5 ± 4.7 mmol/L vs 42.2 ± 9.3 mmol/L, P < 0.05). CONCLUSION: Our results show that UCMSCs can differentiate into islet-like cells in vitro under certain conditions, which can function as IPCs both in vivo and in vitro.

[Cryopreservation of microencapsulated human hepatocytes].

OBJECTIVE: To establish a stable method of isolation, culture and cryopreservation of adult primary hepatocytes to provide potential hepatocyte resources for therapeutic usage in hepatocyte transplantation and bioartificial liver support systems for the treatment of acute and chronic liver diseases,and for experimental usage as an in vitro model of the liver. METHODS: Adult hepatocytes from 20 human donors undergoing partial hepatectomy were isolated using a two-step extracoporeal collagenase perfusion technique.Seven preincubation time points (2h,6h,12h,24h,36h,48h and 72h) were selected for optimization.After pre-incubation at 4 degrees C for 12-24h in HepatoZYME-SFM (the optimal condition),hepatocytes were microencapsulated using alginate-poly-L-lysine-alginate microcapsules,transferred to a complete medium containing 10% dimethyl sulphoxide and immediately placed into an isopropanol progressive freezing container for overnight freezing at -80 degrees C followed by immersion in liquid nitrogen the next day.During the post-thawing culture period,the cells were tested for albumin secretion,urea synthesis,cell cycling,transcription and protein synthesis (measuring mRNA and protein levels),and the morphological structure and pathology,for comparison with the features from before microencapsulated cryopreservation (PMC). RESULTS: The viability and plating efficiency of the hepatocytes isolated using the two-step extracorporeal collagenase perfusion technique were 75.0+/-4.6% and 72.0+/-6.0%,respectively.The pre-incubation times of 12h and 24h (viability:61.4+/-4.8% and 62.0+/-5.6%; plating efficiency:3.2+/-5.8% and 62.6+/-3.6%,respectively) showed significantly higher albumin secretion than all other time points tested (F =40.3,all P less than 0.05).Compared with the immediate cryopreservation (immediately frozen control) hepatocytes,the PMC hepatocytes showed significantly better transcription and protein synthesis and higher albumin secretion and urea levels.The PMC group did not show a significantly different level of albumin production from the directly cultured hepatocytes (culture day 2:ll9.2ng/ml vs.131.36ng/ml,P =0.051; day 3:110ng/ml vs.120.4ng/ml,P=0.063; day 4:98.2ng/ml vs.109.8ng/ml,P more than 0.05).However,over culturing days 2,3 and 4,comparison of the PMC hepatocytes to the immediate cryopreservation hepatoeytes showed the former to have significantly higher secretion of albumin (119.2ng/ml vs.101.2ng/ml,110.0ng/ml vs.87.6ng/ml and 98.2ng/ml vs.73.8ng/ml; all P less than 0.05) and urea level (7.83 mug/ml vs.6.79 mug/ml,6.83 mug/ml vs.5.89 mug/ml and 5.85 mug/ml vs.4.83 mug/ml; all P less than 0.05).The post-thawed PMC hepatoeytes showed preservation of the morphological structure,while the immediate cryopreservation hepatocytes did not. CONCLUSION: The two-step extracorporeal collagenase perfusion technique after partial hepatectomy is a novel,simple,and reliable method for hepatocyte isolation.Pre-incubation at 4 degrees C for 12-24h before the microencapsulation cryopreservation allows for efficient recovery of functional and morphological integrity after thawing and provides viable hepatoeytes that may be useful for clinical applications in pharmacotoxicology,bioartificial liver therapy and cell therapy in humans.

Induction of highly functional hepatocytes from human umbilical cord mesenchymal stem cells by HNF4α transduction.

AIM: To investigate the differentiation potential of human umbilical mesenchymal stem cells (HuMSCs) and the key factors that facilitate hepatic differentiation. METHODS: HuMSCs were induced to become hepatocyte-like cells according to a previously published protocol. The differentiation status of the hepatocyte-like cells was examined by observing the morphological changes under an inverted microscope and by immunofluorescence analysis. Hepatocyte nuclear factor 4 alpha (HNF4α) overexpression was achieved by plasmid transfection of the hepatocyte-like cells. The expression of proteins and genes of interest was then examined by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR) or real-time RT-PCR methods. RESULTS: Our results demonstrated that HuMSCs can easily be induced into hepatocyte-like cells using a published differentiation protocol. The overexpression of HNF4α in the induced HuMSCs significantly enhanced the expression levels of hepatic-specific proteins and genes. HNF4α overexpression may be associated with liver-enriched transcription factor networks and the Wnt/ß-Catenin pathway. CONCLUSION: The overexpression of HNF4α improves the hepatic differentiation of HuMSCs and is a simple way to improve cellular sources for clinical applications.

Types and timing of therapy for vocal fold paresis/paralysis after thyroidectomy: a systematic review and meta-analysis.

OBJECTIVES: To perform a systematic literature review to evaluate the type and timing of therapy for vocal fold paresis/paralysis after thyroidectomy and develop a primary decision-making pathway. STUDY DESIGN: Meta-analysis. METHODS: Four databases and one journal were searched using the key words of "thyroidectomy," "vocal cord paresis/paralysis," and "therapy." Study quality was evaluated using the Cochrane Collaboration's risk of bias tools. Data regarding type and timing of therapy were extracted from 39 articles. Odds ratios (ORs), relative risk (RR), 95% confidence interval, and heterogeneity were recorded. Logistic regression analysis was performed to determine the relationships between timing and OR/RR. RESULTS: Among the 13 studies investigating unilateral paresis/paralysis, five focused on early therapy (0-6 months). In these studies, the OR for clinical heterogeneity was significantly higher after neurolysis than after injection laryngoplasty and voice training (Q = 17.002, I(2) = 78%, P = 0.000), and the RR for heterogeneity was significantly higher after injection laryngoplasty at ≥12 months than <12 months (Q = 9.984, I(2) = 89.9%, P = 0.002). In the 26 studies that investigated bilateral paresis/paralysis, the OR for heterogeneity was significantly higher for bilateral posterior cordectomy than for endolaryngeal laterofixation (Q = 3.510, I(2) = 71.5%, P = 0.061) and laser arytenoidectomy with posterior cordectomy (Q = 2.90, I(2) = 65.6%, P = 0.088). CONCLUSIONS: For unilateral vocal fold paresis/paralysis after thyroidectomy, we recommend absorbable mass injection laryngoplasty, voice training, and neurolysis during the first 12 months but laryngeal reinnervation after 12 months. For bilateral vocal fold paresis/paralysis, we recommend early laterofixation and combined laser arytenoidectomy with posterior cordectomy after 12 months.

Evaluation and integration of existing methods for computational prediction of allergens.

BACKGROUND: Allergy involves a series of complex reactions and factors that contribute to the development of the disease and triggering of the symptoms, including rhinitis, asthma, atopic eczema, skin sensitivity, even acute and fatal anaphylactic shock. Prediction and evaluation of the potential allergenicity is of importance for safety evaluation of foods and other environment factors. Although several computational approaches for assessing the potential allergenicity of proteins have been developed, their performance and relative merits and shortcomings have not been compared systematically. RESULTS: To evaluate and improve the existing methods for allergen prediction, we collected an up-to-date definitive dataset consisting of 989 known allergens and massive putative non-allergens. The three most widely used allergen computational prediction approaches including sequence-, motif- and SVM-based (Support Vector Machine) methods were systematically compared using the defined parameters and we found that SVM-based method outperformed the other two methods with higher accuracy and specificity. The sequence-based method with the criteria defined by FAO/WHO (FAO: Food and Agriculture Organization of the United Nations; WHO: World Health Organization) has higher sensitivity of over 98%, but having a low specificity. The advantage of motif-based method is the ability to visualize the key motif within the allergen. Notably, the performances of the sequence-based method defined by FAO/WHO and motif eliciting strategy could be improved by the optimization of parameters. To facilitate the allergen prediction, we integrated these three methods in a web-based application proAP, which provides the global search of the known allergens and a powerful tool for allergen predication. Flexible parameter setting and batch prediction were also implemented. The proAP can be accessed at http://gmobl.sjtu.edu.cn/proAP/main.html. CONCLUSIONS: This study comprehensively evaluated sequence-, motif- and SVM-based computational prediction approaches for allergens and optimized their parameters to obtain better performance. These findings may provide helpful guidance for the researchers in allergen-prediction. Furthermore, we integrated these methods into a web application proAP, greatly facilitating users to do customizable allergen search and prediction.