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Competing Interests: The authors declare that they have no conflict of interest.

Objective: To determine the serum levels of CMTM6 mRNA and CCN1 in patients with acute leukemia (AL), and to analyze their relationship with the clinical efficacy and prognosis of the patients., Methods: 103 AL patients admitted to our hospital from February 2015 to January 2019 were included as the study subjects. Additionally, 100 healthy subjects who underwent physical examinations during the same period were included as the control group. qRT-PCR method was applied to detect the serum CMTM6 mRNA level of the study subjects, the serum CCN1 level was measured by ELISA. The levels of serum CMTM6 mRNA and CCN1 between the control group and AL patients, as well as between patients at initial diagnosis and after one course of chemotherapy were compared, the correlation of CMTM6 mRNA and CCN1 levels at initial diagnosis with clinicopathological features and short-term efficacy in AL patients was analyzed. The correlation of the CMTM6 mRNA and CCN1 expression levels with prognosis of the patients was analyzed by Kaplan-Meier curves., Results: Compared with the control group, the serum CMTM6 mRNA level in AL patients was significantly increased ( P < 0.05), while the serum CCN1 level was significantly decreased ( P < 0.05). There were no statistically significant differences in serum CMTM6 mRNA and CCN1 levels between patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) ( P >0.05). Compared with those at the initial diagnosis, both the serum CMTM6 mRNA and CNN1 expression levels in AL patients were significantly altered after one course of chemotherapy, with CMTM6 mRNA significantly decreased ( P < 0.05) and CCN1 significantly increased ( P < 0.05). The 3-year recurrence-free survival (RFS) rate was lower in the CMTM6 high expression group and the CCN1 low expression group, compared with the CMTM6 low expression group and CCN1 high expression group, respectively ( P < 0.05)., Conclusion: Serum CMTM6 is highly expressed and CCN1 is lowly expressed in AL patients. The expression levels of serum CMTM6 and CCN1 are associated with the 3-year prognosis of the patients.

Objective: To investigate the clinical characteristics and influence of co-mutated gene on acute myeloid leukemia patients (AML) with FMS-like tyrosine kinase-3 ( FLT3 ) mutations., Methods: A total of 273 FLT3 + AML patients were enrolled, and the co-mutation gene data of the patients were collected to further analyze the prognosis of the patients. FLT3 and other common mutations were quantified by PCR amplification products direct sequencing and second-generation sequencing (NGS)., Results: When patients were divided into FLT3 - ITD + , FLT3 - TKD + , FLT3 - ITD + + TKD + and FLT3 - ITD - + TKD - group according to the type of FLT3 mutations, it was found that the frequencies of TET2 , GATA2, NRAS and ASXL1 mutation were significantly different among the 4 groups (all P < 0.05). When patients were divided into allelic ratio (AR) ≥0.5 and <0.5 group, it was found that the frequencies of FLT3 - ITD + , FLT3 - ITD - + TKD - , NPM1, NRAS and C-kit were significantly different between the two groups (all P < 0.05). When patients were divided into normal and abnormal karyotype group, it was found that the frequencies of FLT3 - ITD + , FLT3 - TKD + , NPM1, GATA2 and C-kit were significantly different between the two groups (all P < 0.05). The median overall survival (OS) of AML patients with FLT3 - TKD + (including FLT3 - ITD + + TKD + ) was longer than that of patients with FLT3 - ITD + alone ( P < 0.05). The OS and relapse-free survival (RFS) of AML patients with FLT3 + + TET2 + were both shorter than those of patients with FLT3 + + TET2 - (both P < 0.05)., Conclusion: The mutation frequencies of co-mutated genes are correlated with subtypes of FLT3 , karyotype and AR. AML patients with FLT3 - TKD + have longer OS than patients with FLT3 - ITD + alone, and patients with co-mutation of TET2 have shorter median OS and RFS.

Quantifying the impact of competition on individual tree biomass and its distribution pattern can provide a basis for improving the prediction accuracy of forest biomass models. To accurately quantify the effects of competition factors on individual biomass and its distribution, we constructed three different individual biomass models by using nonlinear coupling equations based on the biomass survey data of 50 Larix gmelinii from 18 plots of Pangu Forest Farm in Daxing'an Mountains. M-1 was a traditional singly additive biomass model. M-2 and M-3 were models taking the distance dependent simple competition index (CI) and distance independent relative diameter ( R d ) into account, respectively. Those models were used to reveal the influence of competition factors on the prediction accuracy and distribution pattern of single tree biomass model of L. gmelinii . The results showed that the adjusted R 2 of three additive models ranged from 0.694 to 0.974, mean prediction errors ranged from -0.017 to 0.021, and mean absolute errors ranged from 0.152 to 0.357. The introduction of R d could improve the fitting degree and prediction accuracy of most biomass models, but CI did not affect the model fitting effect and prediction ability. Among the three models, M-3 model had the best performance, with good fitting degree and prediction accuracy of the biomass of each part, which could accurately estimate the single tree biomass of L. gmelinii . Further simulation results showed that the variation of biomass with DBH was mainly affected by CI and R d grade, and the influence of R d was stronger than CI. CI had greater influence on root and dry biomass, but less influence on branch and leaf biomass. R d had a more significant effect on biomass of branch and leaf than on that of root and trunk.

The low incidence of combined hepatocellular cholangiocarcinoma (cHCC-CCA) is an important factor limiting research progression. Our study extensively included nearly three decades of relevant literature and assembled the most comprehensive database comprising 5,742 patients with cHCC-CCA. We summarized the characteristics, tumor markers, and clinical features of these patients. Additionally, we present the evolution of cHCC-CCA classification and explain the underlying rationale for these classification standards. We reviewed cHCC-CCA diagnostic advances using imaging features, tumor markers, and postoperative pathology, as well as treatment options such as surgical, adjuvant, and immune-targeted therapies. In addition, recent advances in more effective chemotherapeutic regimens and immune-targeted therapies were explored. Furthermore, we described the molecular mutation features and potential specific markers of cHCC-CCA. The prognostic value of Nestin has been proven, and we speculate that Nestin will also play a role in classification and diagnosis. However, further research is needed. Moreover, we believe that the possibility of using machine learning liquid biopsy for preoperative diagnosis and establishing a scoring system are directions for future research., Competing Interests: The authors declare that there is no conflict of interest in this study., (© The Author(s) 2024. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Background: Hepatic pedicle clamping (HPC) is frequently utilized during hepatectomy to reduce intraoperative bleeding and diminish the need for intraoperative blood transfusion (IBT). The long-term prognostic implications of HPC following hepatectomy for hepatocellular carcinoma (HCC) remain under debate. This study aims to elucidate the association between HPC and oncologic outcomes after HCC resection, stratified by whether IBT was administered., Patients and Methods: Prospectively collected data on patients with HCC who underwent curative resection from a multicenter database was studied. Patients were stratified into two cohorts on the basis of whether IBT was administered. The impact of HPC on long-term overall survival (OS) and recurrence-free survival (RFS) between the two cohorts was assessed by univariable and multivariable Cox regression analyses., Results: Of 3362 patients, 535 received IBT. In the IBT cohort, using or not using HPC showed no significant difference in OS and RFS outcomes (5-year OS and RFS rates 27.9% vs. 24.6% and 13.8% vs. 12.0%, P = 0.810 and 0.530). However, in the non-IBT cohort of 2827 patients, the HPC subgroup demonstrated significantly decreased OS (5-year 45.9% vs. 56.5%, P < 0.001) and RFS (5-year 24.7% vs. 33.3%, P < 0.001) when compared with the subgroup without HPC. Multivariable Cox regression analysis identified HPC as an independent risk factor of OS and RFS [hazard ratios (HR) 1.16 and 1.12, P = 0.024 and 0.044, respectively] among patients who did not receive IBT., Conclusions: The impact of HPC on the oncological outcomes following hepatectomy for patients with HCC differed significantly whether IBT was administered, and HPC adversely impacted on long-term survival for patients without receiving IBT during hepatectomy., (© 2023. Society of Surgical Oncology.)

Gastric cancer (GC) is one of the most prevalent malignant tumors of the gastrointestinal system in the globe. The effect of PIEZO2 on the immune function and pathological features of gastric cancer remains to be explored. The Online database of cancer genes and GSE54129 have been used to analyze the clinical characteristics of PIEZO2 expression. We looked at the relationship between PIEZO2 and the immune systems of GC patients. The TIDE algorithm was used to explore the value of PIEZO2 in immunotherapy. Investigated the enrichment of PIEZO2 gene ontology and associated signal pathways using Online gene databases. The results show that overexpression of PIEZO2 was identified as an independent risk factor for patients with GC who had poor overall survival. Individuals may have a better prognosis if they had poorly differentiated GC and increased PIEZO2 expression (P < 0.05). We demonstrated a strong correlation between PIEZO2 and immune cells. The majority of immune checkpoint and immunological-related genes were associated with PIEZO2 expression. And PIEZO2 might be used as an immunotherapy target. Finally, the differential PIEZO2 genes in GC were mostly implicated in the processes of inflammation, immunological response, and tumor metastasis, according to functional analysis. PIEZO2 has a negative correlation with cell stemness and mutation levels in patients with GC and a positive correlation with immune cell infiltration and gene expression in the tumor microenvironment. These findings point to PIEZO2 as a potential new immunotherapy target of GC., (© 2023. The Author(s).)

For patients with cardiovascular disease, using the antidepressant escitalopram may lead to unexpected adverse events. Here, a rare repeated sinus bradycardia event due to escitalopram is first reported. In an 82-year-old female patient with cardiac dysfunction using digoxin, tachycardia (average heart rate of 93 beats/min) was demonstrated by electrocardiogram (ECG). She began to take escitalopram and lorazepam due to depression, but sinus bradycardia (93.7% heart rate was <60 beats/min) and sinus arrest were first detected after 3 months. Its proportion decreased to 0.1% after discontinuation of digoxin and escitalopram for 1 day, and the rhythm returned to normal 2 weeks later. After 2 months, escitalopram was prescribed again in combination with quetiapine; then, 17.1% heart rate was <60 beats/min. After escitalopram and quetiapine withdrawal, the ECG showed the heart rhythm had normalized again. No other drug changes were made during these periods. Escitalopram was deemed to be a highly possible cause of sinus bradycardia according to its Naranjo's Algorithm score. Furthermore, literature on escitalopram-mediated cardiovascular adverse events was reviewed and analyzed. Empirically, escitalopram should be discontinued immediately if iatrogenic causes cannot be ruled out. Furthermore, ECG monitoring in escitalopram-related cardiovascular adverse events is highlighted, especially in patients receiving certain drug classes simultaneously (i.e., sinoatrial node inhibitors, antipsychotics)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Li, Sun, Lv, Xu, Hu and Shi.)

Background: The causation of Glycemic Traits and risks of Melanoma remains unknown. We used Mendelian Randomization (MR) to assess the links between Glycemic Traits and Melanoma. Method: Pooled data from Genome-Wide Association Studies (GWAS) were utilized to examine the relationships that exist between Fasting Insulin (n = 26), 2-h Glucose (n = 10), Fasting Glucose (n = 47), HbA1c (n = 68), and Type-2 Diabetes (n = 105) and Melanoma. We evaluated the correlation of these variations with melanoma risk using Two-Samples MR. Result: In the IVW model, Fasting Glucose (OR = 0.99, 95%CI = 0.993-0.998, p < 0.05, IVW), Type-2 Diabetes (OR = 0.998, 95%CI = 0.998-0.999, p < 0.01, IVW) and HbA1c (OR = 0.19, 95%CI = 0.0415-0.8788, p < 0.05, IVW) was causally associated with a lower risk of Melanoma. In all models analyzed, there was no apparent causal relationship between Fasting Insulin and Melanoma risk. There was no obvious causal difference in the IVW analysis of 2-h Glucose and Melanoma, but its p < 0.05 in MR Egger (OR = 0.99, 95%CI = 0.9883-0.9984, p < 0.05, MR Egger), and the direction was consistent in other MR analyses, suggesting that there may be a causal relationship. Conclusion: The results of this study suggest that a higher risk of Fasting Glucose, Type-2 Diabetes, 2-h Glucose, and HbA1c may be associated with a lower risk of Melanoma. However, no causal relationship between fasting insulin and melanoma was found. These results suggest that pharmacological or lifestyle interventions that regulate plasma glucose levels in the body may be beneficial in the prevention of melanoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Lu, Li, Shi, Shi and Yang.)

UPLC-Q-Exactive-MS/MS and network pharmacology were employed to preliminarily study the active components and mechanism of Jinwugutong Capsules in the treatment of osteoporosis. Firstly, UPLC-Q-Exactive-MS/MS was employed to characterize the chemical components of Jinwugutong Capsules, and network pharmacology was employed to establish the &quot;drug-component-target-pathway-disease&quot; network. The key targets and main active components were thus obtained. Secondly, AutoDock was used for the molecular docking between the main active components and key targets. Finally, the animal model of osteoporosis was established, and the effect of Jinwugutong Capsules on the expression of key targets including RAC-alpha serine/threonine-protein kinase(AKT1), albumin(ALB), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA). A total of 59 chemical components were identified from Jinwugutong Capsules, among which coryfolin, 8-prenylnaringenin, demethoxycurcumin, isobavachin, and genistein may be the main active components of Jinwugutong Capsules in treating osteoporosis. The topological analysis of the protein-protein interaction(PPI) network revealed 10 core targets such as AKT1, ALB, catenin beta 1(CTNNB1), TNF, and epidermal growth factor receptor(EGFR). The Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment showed that Jinwugutong Capsules mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, neuroactive ligand-receptor interaction, mitogen-activated protein kinase(MAPK) signaling pathway, Rap1 signaling pathway and so on. Molecular docking showed that the main active components of Jinwugutong Capsules well bound to the key targets. ELISA results showed that Jinwugutong Capsules down-regulated the protein levels of AKT1 and TNF-α and up-regulated the protein level of ALB, which preliminarily verified the reliability of network pharmacology. This study indicates that Jinwugutong Capsules may play a role in the treatment of osteoporosis through multiple components, targets, and pathways, which can provide reference for the further research.

Hepatitis C virus (HCV) genotypes vary greatly in different regions. The aim of this study is to investigate the distribution of HCV genotypes in HCV infected patients, in Ningxia Hui Autonomous Region. Nucleic acid extraction and amplification were performed with test kits on 153 HCV infected patients serum samples. The HCV viral load was measured using reverse transcriptase PCR (RT-PCR) and HCV genotypes were determined. Among the 153 HCV-infected patients, 56 had genotype (GT)1b (36.60%), 45 had GT2a (29.40%), 23 had GT3a (15.00%), 14 had GT3b (9.20%),13 had GT6a (8.50%), 1 had GT1g (0.70%), 1 had GT6xa (0.70%). In GT1b, 21.40% were female and 78.60% were male; in GT2a, 42.20% were female and 57.80% were male;Males were most prevalent in genotypes 1b(39.30%), while female were most prevalent in genotype 2a(46.30%). Rare GT1g and GT6xa were also detected in males. The 41-50 year age group had the highest HCV prevalence of 32.00%. HCV GT1b is the predominant HCV genotype in Ningxia Hui Autonomous Region.

Background: The immune landscape, prognostic model, and molecular variations of mantle cell lymphoma (MCL) remain unclear. Hence, an integrated bioinformatics analysis of MCL datasets is required for the development of immunotherapy and the optimization of targeted therapies., Methods: Data were obtained from the Gene Expression Omnibus (GEO) database (GSE32018, GSE45717 and GSE93291). The differentially expressed immune-related genes were selected, and the hub genes were screened by three machine learning algorithms, followed by enrichment and correlation analyses. Next, MCL molecular clusters based on the hub genes were identified by K-Means clustering, the probably approximately correct (PAC) algorithm, and principal component analysis (PCA). The landscape of immune cell infiltration and immune checkpoint molecules in distinct clusters was explored by single-sample gene-set enrichment analysis (ssGSEA) as well as the CIBERSORT and xCell algorithms. The prognostic genes and prognostic risk score model for MCL clusters were identified by least absolute shrinkage and selection operator (LASSO)-Cox analysis and cross-validation for lambda. Correlation analysis was performed to explore the correlation between the screened prognostic genes and immune cells or immune checkpoint molecules., Results: Four immune-related hub genes ( CD247, CD3E, CD4 , and GATA3 ) were screened in MCL, mainly enriched in the T-cell receptor signaling pathway. Based on the hub genes, two MCL molecular clusters were recognized. The cluster 2 group had a significantly worse overall survival (OS), with down-regulated hub genes, and a variety of activated immune effector cells declined. The majority of immune checkpoint molecules had also decreased. An efficient prognostic model was established, including six prognostic genes ( LGALS2, LAMP3, ICOS, FCAMR, IGFBP4 , and C1QA ) differentially expressed between two MCL clusters. Patients with a higher risk score in the prognostic model had a poor prognosis. Furthermore, most types of immune cells and a range of immune checkpoint molecules were positively correlated with the prognostic genes., Conclusions: Our study identified distinct molecular clusters based on the immune-related hub genes, and showed that the prognostic model affected the prognosis of MCL patients. These hub genes, modulated immune cells, and immune checkpoint molecules might be involved in oncogenesis and could be potential prognostic biomarkers in MCL., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-5815/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Cardiac fibrosis is a major structural change observed in the heart of patients with type 2 diabetes mellitus (T2DM), ultimately resulting in heart failure (HF). Suppression of inflammation is an effective therapeutic strategy for treating cardiac fibrosis and HF. Gentiopicroside (GPS), the primary component of Gentiana manshurica Kitagawa, possess potent anti-inflammatory activity. However, its cardioprotective role remains elusive., Purpose: We explored the potential cardioprotective role of GPS in T2DM rats and its underlying mechanisms., Methods: T2DM rats built by high-fat diet and streptozotocin were orally administered 25, 50, or 100 mg/kg GPS, daily for 8 weeks. The positive control drug was Metformin (200 mg/kg/day). Primary cardiac fibroblasts (CFs) were induced by high glucose (30 mM) and subsequently treated with GPS (100 μM). Cardiac function and pathological changes were analyzed using echocardiography and histological staining. Potential targets of GPS were predicted using Molecular docking. Real-time PCR as well as western blotting were applied to verify the expression of objective genes., Results: All three doses reduced fasting blood glucose levels, but only 50 and 100 mg/kg GPS improved cardiac function and alleviated inflammation and fibrosis in T2DM rats. GPS (100 mg/kg) exhibited a better effect, similar to that of metformin. Mechanistically, binding between GPS and the MH2 domain of Smad3 blocked high glucose-induced Smad3 phosphorylation, thus attenuating inflammation, oxidative stress, and activation in CFs., Conclusion: We, for the first time, demonstrated that GPS improved cardiac function in T2DM rats and elucidated the underlying mechanism through which GPS targeted Smad3 phosphorylation to suppress inflammation and activation in CFs, thereby revealing the potential application of GPS in HF therapy., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Aim: Coregonus peled fillets were used as a model to evaluate the dominant bacterial growth of chilled fish during storage after shipping and interactions of selected bacterial strains., Methods and Results: Coregonus peled fillets were transported by air and land in ice boxes about 48 h from aquatic products company in Xinjiang, China, to the laboratory located in Dalian, China. Both culture-dependent (plate counts on nonselective media) based on 16S rRNA gene sequencing and culture-independent (Illumina-MiSeq high-throughput sequencing) methods were used. To detect interactions among bacterial populations from chilled fish, the influence of 18 test strains on the growth of 12 indicator isolates was measured by a drop assay and in liquid culture medium broth. The results showed that bacterial counts exceeded 7.0 log CFU/g following storage for 4 days at 4 °C. When the bacterial counts exceeded 8.5 log CFU/g after 12 days, the predominant micro-organisms were Aeromonas, Pseudomonas, Carnobacterium, Psychrobacter and Shewanella, as measured by the culture-independent method. All test strains showed inhibiting effects on the growth of other strains in liquid culture. Pseudomonas isolates showed antibacterial activity for approximately 60% of the indicator strains on nutritional agar plates. The majority of test isolates enhancing indicator strain growth were the strains isolated on day 0., Conclusions: High-throughput sequencing approach gives whole picture of bacterial communities in chilled C. peled fillets during storage, while growth interferences between selected bacterial strains illustrate the complexity of microbial interactions., Significance and Impact of the Study: We determined the bacterial communities and growth interferences in chilled Coregonus peled after shipping and these are the first data concerning microbiota in C. peled using a culture-independent analysis. The present study will be useful for manufacture and preservation of C. peled products by providing with valuable information regarding microbiological spoilage of C. peled., (© 2022 Society for Applied Microbiology.)

Objective: To investigate the clinical characteristics and prognosis of hematological malignancies superimposed patients with solid tumors., Methods: The clinical data of 30 patients with more than two kinds of malignancy (the second is hematological malignancy) from October 2011 to October 2020 in Department of Hematology, Jiangning Hospital Affiliated to Nanjing Medical University were collected and analyzed retrospectively. The overall survival time was used as the prognostic evaluation standard, and the survival of patients were analyzed by KaplanMeier method. Logrank test and Cox regression model were used to carry out univariate and multivariate retrospective analysis on clinical and laboratory parameters of 30 patients., Results: Among 30 cases, 20 were male, 10 were female, the median age of onset of the second tumor was 70 years old. The common types of the secondary hematological malignancies to solid tumors are myelodysplastic syndrome, acute myeloid leukemia, multiple myeloma. Univariate analysis showed that patients' gender, age, type of solid tumors, the onset of interval between two kinds of tumor, chromosome karyotype were not related to do with the patients' overall survival time. Type of hematologic disease, ECOG score were associated with patients' overall survival time, and the multivariate analysis showed that the type of hematologic disease and ECOG score were independent risk factors for patients with poor prognosis., Conclusion: Patients superimposed with solid tumors complicated with myelodysplastic syndrome or acute leukemia and ECOG score ≥3 have poor prognosis and shorter overall survival time, which are independent risk factors influencing the prognosis. Bone marrow injury, immune dysfunction and genetic susceptibility after chemoradiotherapy may be the main causes of these diseases.

Background: Studies have given some pieces of evidence for the effect of total knee arthroplasty (TKA) on knee proprioception of patients with knee osteoarthritis (KOA), but their results were conflicting. This review was performed to provide an updated evidence-based meta-analysis investigating the influence of TKA on knee proprioception., Methods: The electronic databases including PubMed, Google Scholar, and the Cochrane Library were accessed from their inception to March 2020. Two reviewers identified the studies that met the selection criteria for this review. Information on study type, participants, follow-up time, and outcome measures was extracted. Methodological quality was independently assessed by two reviewers using the Cochrane Handbook 5.1.0. Eleven studies with 475 participants were included in the meta-analysis., Results: The I 2 index assessed the heterogeneity between studies. The results showed that the pooled standard mean difference of mean angle of error was - 0.58° (95% CI - 1 to - 0.16; P = 0.007; I 2  = 69%), and the joint position sense of KOA patients was better after TKA surgery than that before surgery. Pooled standard mean difference of displacement of center of pressure (COP) was - 0.39 (95% CI - 0.72 to - 0.06; P = 0.02; I 2  = 51%), and KOA patients had better static balance after TKA surgery than before surgery., Conclusions: To conclude, no standardized comprehensive evaluation protocol presently exists though different assessment tools are available to measure proprioception. Contrasting results were found in the literature since some studies found that TKA improves proprioception in KOA patients, while others found no difference in proprioception. These differences are seen whether the proprioception was assessed by joint position sense (JPS), or it was indirectly assessed by static balance. However, the lack of sufficient data on the threshold to detect passive movement (TTDPM) and dynamic balance made it difficult to draw a conclusion about whether or not the sense of motion improved after surgery. The method for measuring and evaluating knee joint force sense is worth paying attention, which will make progress with knee proprioception on TKA patients., (© 2022. The Author(s).)

Background: The number of obese people continues to increase worldwide, and obesity-related complications add to every country's health burden. Consequently, new weight-loss medications, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), are attracting increasing attention. This study sought to assess the cost effectiveness for weight loss of 4 GLP-1RAs in adult patients with obesity in the United States., Methods: Four GLP-1RA groups that received Liraglutide (1.8 mg QD), Semaglutide (1.0 mg QW), Dulaglutide (1.5 mg QW), or Exenatide (10 μg BID), and one no-treatment group were compared using a decision-tree model. All the estimated parameters were derived from published articles. Quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs) were adopted as the study endpoints. We analyzed the results with the willingness-to-pay (WTP) threshold, and conducted deterministic and probabilistic sensitivity analyses., Results: The GLP-1RAs produced effective weight-loss results; however, not all the GLP-1RAs were cost effective compared to no treatment based on a WTP threshold of $195000/QALY. Among the 4 GLP-1RAs, Semaglutide provided a cost-effective strategy with an ICER of $135467/QALY. The sensitivity analyses showed that these results are reliable., Conclusions: Among the 4 GLP-1RAs, Semaglutide was the most cost-effective obesity medication., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-200/coif). The authors have no conflict of interests to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Cetuximab is an IgG1 chimeric mAb against epidermal growth factor receptor, which can be used for chemotherapy failure or tolerance in patients with epidermal growth factor receptor expressed RAS wild-type metastatic colorectal cancer. We report on a patient who developed rapid-onset interstitial pneumonia while being treated with cetuximab plus XELOX (oxaliplatin, capecitabine) for metastatic colorectal cancer. A 75-year-old man patient was administered cetuximab plus XELOX regularly. After his cetuximab schedule was adjusted from 1 to 2 weeks, he rapidly developed interstitial pneumonia which led to acute respiratory distress syndrome. Our literature review indicated that, for patients with risk factors, a 2-week regimen of cetuximab might lead to interstitial pneumonia. Clinicians should closely monitor patients for adverse drug reactions to improve drug safety., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To explore the non-genetic factors of overall survival in patients with multiple myeloma (MM)., Methods: Kaplan-Meier survival curve, Log-rank test and Cox regression model were used to carry out univariate and multivariate retrospective analysis on clinical and laboratory parameters of 51 patients who were newly diagnosed with MM and had complete follow-up data in the Department of Hematology, the Affiliated Jiangning Hospital of Nanjing Medical University from November 2011 to October 2019., Results: Fifty-one patients included 29 males and 22 females. Followed up to December 2019, 21 cases died and 30 cases survived. The univariate analysis showed that the overall survival time of the patients was influenced by age, disease stage, standard treatment, new drugs, maintenance treatment, hypercalcemia, globulin, albumin, and hemoglobin. The overall survival time of patients with age <65 years old, ISS stage I and II, standardized treatment, new drugs, normal or below normal blood calcium, normal or below normal globulin, albumin ≥35 g/L or hemoglobin ≥100 g/L was prolonged significantly (P<0.05). The multivariate analysis showed that maintenance treatment, hypercalcemia (≥2.6 mmol/L), and hemoglobin (<100 g/L) were independent risk factors influencing the prognosis of MM patients., Conclusion: Patients with blood calcium ≥2.6 mmol/L, hemoglobin <100 g/L, and who do not undergo regular maintenance therapy show a poor prognosis.

With landsat-series multi-temporal image data, percentage of vegetation cover (PVC) was estimated by pixel dichotomy. The linear regression analysis and center of gravity migration methods were used to explore the characteristics of the spatiotemporal changes of vegetation cover in Shenzhen from 2000 to 2018. The CA-Markov model was combined to predict future land cover in Shenzhen. The results showed that the PVC in Shenzhen demonstrated obvious regional differentiation characteristics from 2000 to 2018. The eastern region occupied larger proportion than the wes-tern part, while the southern region was larger than the north part. This feature exhibited good consistency with regional topographic effect. The spatial migration characteristic of the center of gravity of PVC was from northwest to southeast, and then from southeast to northwest, with a migration rate of 551.2 m·a -1 . This process was closely related to urbanization in Shenzhen. The PVC in Shen-zhen tended to be generally improved from 2000-2018, with a improvement rate of 0.005·a -1 . The percentage of significantly improved and degraded PVC area was 30.8% and 12.8%, respectively. The CA-Markov method was used to predict the land cover/use pattern of Shenzhen in 2024 under two scenarios, theoretical scenario and natural scenario. There was no significant difference in proportion of the area of the land cover/use patterns obtained by the two kinds of prediction method, with the difference threshold being 0-1.2%. Compared with the data before 2018, the proportion of arbor forests and arable land converted into construction land in Shenzhen would be significantly reduced in 2024, whereas the contradiction between supply and demand would be still tense.

Objective: To investigate the transfusion effectiveness of suspended leucocyte depleted red blood cells (sld RBC) and fresh and irradiated apheresis platelets (fia Plt) in patients with myelodysplastic syndromes (MDS), and to explore the causes and mechanisms of ineffective platelet transfusion in patients with MDS., Methods: Clinical data of 37 patients with confirmed MDS (WHO standard) such as the sex, age, Hb levels, Plt count, hemorrhage and coagulation functions, TEG and so on, were retrospectively analyzed., Results: Among the 37 patients, 15 patients (40.5%) received only sld RBC transfusion, 9 patients (24.3%) received only fia Plt transfusion, and 13 patients (35.1%) received both transfusion. Among the 15 patients with only red blood cell transfusion, 3 patients were ineffective and the ineffectual transfusion rate was 20.0%. Among the 9 patients with only received platelet transfusion, 5 patients were ineffective and the ineffectual transfusion rate was 55.6%, there were significant statistical differences between the two groups (P﹤0.01). The red blood cell transfusion ineffective were 3 patients (23.1%) , the platelet transfusion ineffective were 8 patients (61.5%) and the both transfusion ineffective were 2 patients (15.4%) among the patients both transfusion . The positive rate of platelet antibody in MDS patients with ineffective platelet transfusion was 23.1%. Compared with the normal control group, Human P selectin (P-SelectinCD62P) (P＜0.001) and human anti-thrombin 3 antibody (AT-III Ab) (P＜0.001) significantly increased and human tissue factor pathway inhibitor (TFPI) significantly decreased (P＜0.05) in MDS patients with ineffective platelet transfusion., Conclusion: In the process of component transfusion for MDS patients, compared with the transfusion of red blood cells, the inefficiencies of platelet transfusion significantly increased, mainly due to the disorder of blood coagulation and the generation of platelet antibodies in MDS patients with ineffective platelet transfusion. Compared with the normal control group, human P selectin and human anti-thrombin 3 antibody significantly increase and human tissue factor pathway inhibitor significantly decreases in MDS patients with ineffective platelet transfusion. Human P selectin, human anti-thrombin 3 antibody and human tissue factor pathway inhibitor in molecular markers and fibrinolytic markers can be used as indicators of platelet transfusion time and efficiency in patients with MDS.

For chondrosarcoma, metastasis to the thyroid gland is extremely rare. The diagnosis and treatment of thyroid metastasis from chondrosarcoma are discussed here.We found a case of thyroid malignancy occurring after treatment of chondrosarcoma. We reviewed patient characteristics, histological presentations on initial chondrosarcoma and thyroid metastasis, treatments, times of recurrence and death. In addition, we searched Embase, PubMed, and ISI Web of Science databases (1996-2018) for articles published in the English language using the key words "chondrosarcoma" and "thyroid" and we reviewed almost all the reports about thyroid metastasis from chondrosarcoma.Only 5 cases of chondrosarcoma metastases in the thyroid gland have been reported in the literature. We found that most patients are adults, with compression signs or pain, most of whom have poor prognoses. The main examinations are ultrasound, CT and fine needle aspiration biopsy, and primary treatment is surgery.These rare cases of chondrosarcoma presenting as a metastasis in the thyroid gland highlight the importance of close communication between radiologists, histopathologists, and clinicians to ensure that such exceptional cases are not missed.

Bevacizumab (BEV) is widely used for the treatment of patients with recurrent glioblastoma (GBM), but recent evidence demonstrated that BEV induced cytoprotective autophagy, which allows tumor cells to survive. Hydroxychloroquine (HCQ) inhibits lysosomal acidification and blocks autophagy via influencing autophagosome fusion and degradation. HCQ is often used to enhance the efficacy of chemoradiotherapy. However, whether HCQ sensitizes GBM cells to BEV and the molecular mechanism of this effect are not clear. We showed that high concentrations of BEV increased the LC3-II/LC3-I ratio and caused the degradation of Beclin1 in the LN18 and LN229 cell lines, indicating that high concentrations of BEV induced the autophagy of the LN18 and LN229 cells. However, BEV (100 μg/ml) did not influence the autophagy of the LN18 and LN229 cells, and HCQ at less than 5 μg/ml significantly accumulated LC3B-II and p62 proteins and blocked the autophagy process. Importantly, we found that HCQ (5 μg/ml) potentiated the anti-cancer effect of BEV (100 μg/ml). Therefore, HCQ is a novel strategy that may augment the efficacy of BEV for GBM via the inhibition of autophagy., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Non-thyroid malignancies to the thyroid gland resulting from distant metastases are extremely rare, and such cases are rarely seen in clinical settings. The question of how a tumor metastasizes to the thyroid remains unanswered. Here we report a case of lung adenocarcinoma metastasizing to the thyroid gland. The article covers the pathological features, treatments, examination reports, and the postoperative follow-up reviews of the patient. In this article, we discuss the diagnostic method, the spread route, the prognosis, the mechanism and above all, the treatment. In addition, we searched the PubMed and ISI Web of Science databases for articles published in English using the key words "lung", "thyroid", and "metastasis", and we reviewed nearly all the reports about thyroid malignancies being metastasized from lung cancer. This rare case emphasizes the importance of the multifaceted comprehensiveness of the cephalometry diagnosis, pathological diagnosis, and immunohistochemical analysis to ensure that such rare cases are not missed. We declare that all cases of thyroid malignancies metastasized from the lungs shall be reported at large for further clinical research., Competing Interests: None., (IJCEP Copyright © 2019.)

Objective: To investigate the surgical treatment of secondary hyperparathyroidism(SHPT) with thyroid nodule(TN) in uremic patients. Method: The clinical data of 26 patients diagnosed as SHPT combined with TN were retrospectively analyzed. Result: The patients underwent total parathyroidectomy and parathyroid granuless were transplanted subcutaneously into the forearm. The levels of parathyroid hormone,alkaline phosphatase,serum calcium,serum phosphorus and calcium-phosphorus product in 6 months and 12 months after operation were significantly lower than those before operation( P <0.01).The quality of life assessed by KDQOL-SF scale was significantly higher than that before operation( P <0.01). Concomtiant TN was operated simultaneously, and gravel calcification was significantly associated with papillary thyroid carcinoma( P <0.01). Conclusion: Total parathyroidectomy plus subcutaneous minimal forearm autograft and concurrent surgery with TN are feasible, and can not only properly treat TN, but also significantly improve SHPT-related prognosis and quality of life. We should be alert to the possibility of malignant TN in SHPT background, especially those with grit calcification., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Based on dendrochronological methods, we established residual chronologies of Pinus koraiensis and Picea jezoensis, with the dominant species of broadleaved Korean pine mixed forest at low altitudes chosen as the research object, to identify the key climatic factors affecting the radial growth of the two species in Xiaoxing'anling Mountains, Northeast China. The results showed that the responses of the two species to climate factors were different, and P. koraiensis was more sensitive, and hence more suitable for dendroclimatological analysis. Response function coefficients indicated that the radial growth of P. koraiensis negatively correlated with June mean temperature of current year, while positively correlated with precipitation in June of current year. There was no significant correlation between P. jezoensis and all climate variables. Spatial correlation analysis revealed that variations in chronology of P. koraiensis contained strong regional signals, and the highest correlation occurred in the vicinity of the study area. Warming caused drought stress, which was the main factor that limited the growth of P. koraiensis, and it might have adverse effects on the Korean pine if global temperature continues to increase. The coupling effects of large-scale atmospheric-oceanic variability may affect the radial growth of P. koraiensis in Xiaoxing'anling Mountains.

Catalpa sawdust was respectively pretreated by NaOH, Ca(OH)2, H2SO4 and HCl solution, and the enzymatic hydrolysis of catalpa sawdust was significantly enhanced by alkaline pretreatments. In order to investigate the mechanisms of pretreatment of catalpa sawdust, the characteristics of catalpa sawdust before and after pretreatments were analyzed by scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. It was found that the surface of catalpa sawdust was disrupted by four kinds of chemical pretreatment, and the pretreatment with Ca(OH)2 solution resulted in the most serious damage. The XRD results showed that part of amorphous regions was damaged by alkaline pretreatments, which led to a relative increase of crystallinity Index (CrI) of catalpa sawdust; while the CrI of catalpa sawdust was insignificantly influenced by acid pretreatments. The FTIR analysis displayed that the molecular structures of hemicellulose and lignin of catalpa sawdust were damaged in different degrees by four types of pretreatment. The significant improvement of enzymatic hydrolysis of catalpa sawdust after alkaline pretreatment might be attributed to the effective delignification of alkaline.

Transcription factors regulate alteration of transcription levels. Recently, huge amount of transcriptomic data are accumulated via the application of high throughput sequencing technology, and it is reasonable to postulate that in-depth analysis of transcription data could be used to enhance gene annotation. In this study, we chose the gene family of rice WRKY transcription factors. Based on literature search, the transcriptional data under different biological processes, including biotic and abiotic stress, development, and nutrient absorption and hormone treatments were analyzed systematically. To the end, we summarize the list of differentially expressed WRKY genes. We also expect that such information will enrich their functional annotation and also provide direct clues for subsequent functional studies.

Cancer is the most common disease worldwide, with death often occurring as a result of metastasis. Thus, interfering with metastasis has been regarded as a promising strategy to improve the current cancer treatments. However, exploration and development of novel anti-metastatic agents remains a major challenge. Recent evidence indicated that a polysaccharide isolated from Taxus yunnanensis suppressed tumor cells proliferation. With the objective of seeking bioactive extracts, we had previously isolated, purified and characterized a complex, water-soluble polysaccharides, PSY-1, from the leaves of Taxus chinensis var. mairei, and identified its anti-neoplastic effects. In this study, we focused on the effects of PSY-1 on cancer metastasis and its mechanism(s). The results illustrated that PSY-1 effectively suppressed the migration and invasion ability of the melanoma cancer cell line B16-F10, caused down-regulation of MMP-2 and MMP-9, and that the NF-kappaB pathway was involved in the anti-metastatic effects imposed by PSY-1.

Interleukin-17A (IL-17A) is a multifunctional cytokine which plays a crucial role in the initiation and progression of cancer. To date, several studies have investigated associations between IL-17A -197G>A (rs2275913) polymorphism and digestive cancer risk, but the results remain conflicting. We here aimed to confirm the role of this single nucleotide polymorphism (SNP) in susceptibility to digestive cancer through a systemic review and meta-analysis. Ten eligible case-control studies were identified by searching electronic databases, involving 3,087 cases and 3,815 controls. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the strength of the association. The results of overall analyses indicated that the variant A allele was associated with an increased risk of digestive cancer (AA vs GG: OR=1.51, 95%CI=1.18-1.93; AA vs GG+GA: OR=1.45, 95%CI=1.12-1.87; A vs G: OR=1.21, 95%CI=1.05-1.39). In subgroup analysis stratified by specific cancer type, elevated risk among studies of gastric cancer was found (AA vs GG: OR=1.68, 95%CI=1.24-2.28; AA vs GG+GA: OR=1.62, 95%CI=1.16-2.26; A vs G: OR=1.23, 95%CI=1.04-1.46). According to ethnicity, there was evidence in the Asian populations for an association between this polymorphism and cancer risk (GA vs GG: OR=1.19, 95%CI=1.05-1.36; AA vs GG: OR=1.56, 95%CI=1.15-2.12; AA+GA vs GG: OR=1.28, 95%CI=1.13- 1.44; AA vs GG+GA: OR=1.42, 95%CI=1.01-2.00; A vs G: OR=1.24, 95%CI=1.08-1.44), while in the Caucasian populations an association was found in the recessive model (AA vs GG+GA: OR=1.62, 95%CI=1.17-2.24). In conclusion, the results of this meta-analysis suggest that the IL-17A -197G>A polymorphism contributes to an increased risk of human digestive cancer, both in the Asian and Caucasian populations and especially for gastric cancer.

Pales pavida Meigen is obligated polyparasitic fly and important natural enemy of some most damaging forest or agricultural pests, and thus could contribute to the biological control of them. The external morphology of main olfactory organs in this tachinid was examined using stereopic microscopy and scanning electron microscopy, and types, distribution and density of sensilla were provided. The first two antennal segments, antennal scape and pedicel, are covered by microtrichiae and several mechanoreceptors. A pedicellar button is detected on antennal pedicel as well, after its separation with antennal funiculus. On antennal funiculus, five types of sensillar structures are observed including trichoid, basiconic, coeloconic, clavate sensilla and sensory pit with subtype II basiconic sensilla and a type of rarely described coeloconic-like sensilla in it, respectively. There are two specific sensillar characteristics of Pales pavida, two types of sensory pit on antennal funiculus and lower densities of all sensilla types than relatively monoparasitic species, which may serve as applicable evidence on their adaption to environment and lifestyle. Besides, the morphology of pedicellar button in tachinids is first addressed, armed with a discussion of their possible function., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Conflict control is an important cognitive control ability and it is also crucial for human beings to execute conflict control on affective information. To address the neural correlates of cognitive control on affective conflicts, the present study recorded event-related potentials (ERPs) during a revised Eriksen Flanker Task. Participants were required to indicate the valence of the central target expression while ignoring the flanker expressions in the affective congruent condition, affective incongruent condition and neutral condition (target expressions flanked by scramble blocks). Behavioral results manifested that participants exhibited faster response speed in identifying neutral target face when it was flanked by neutral distractors than by happy distractors. Electrophysiological results showed that happy target expression induced larger N2 amplitude when flanked by sad distractors than by happy distractors and scramble blocks during the conflict monitoring processing. During the attentional control processing, happy target expression induced faster P3 response when it was flanked by happy distractors than by sad distractors, and sad target expression evoked larger P3 amplitude when it was flanked by happy distractors comparing with sad distractors. Taken together, the current findings of temporal dynamic of brain activity during cognitive control on affective conflicts shed light on the essential relationship between cognitive control and affective information processing.

Previous work from our laboratory suggests that paradoxical sleep deprivation (PSD) decreases persistent sodium currents and hyperpolarization-activated cation currents in CA1 pyramidal neurons, and this leads to decreases in neuron excitability. Here, we further investigate the mechanisms of rhythmic theta-range activity in the hippocampus by examining the resonance characteristics of hippocampal pyramidal neurons. Sleep deprivation (SD) interfered with the rhythmic activity of theta band in the hippocampus, which may be involved in the deficit of the spatial learning ability of rats. Additionally, SD changes the voltage dependence of resonance. The effect of SD on the ion currents may contribute to the alternation of the theta resonance of neurons and further influence the physiological function. These results suggest that changes in neuron resonance lead to changes in the generation of rhythmic theta activity, and may contribute to behavioral deficits associated with theta activity during learning and memory tasks. We suggest the resonant properties of hippocampal neurons are potential targets for preventing deleterious effects of sleep deprivation., (© 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)

Objective: To identify the active material of anti-hepatic fibrosis from Amydae Carapax., Methods: Membrane separation technology was adopted to screen active fraction in Amydae Carapax, and the active components were isolated from the active fraction using gel chromatography and high performance liquid chromatography. The purified active components in Amydae Carapax were further analyzed using 4700 series time-of-flight mass spectrometer., Results: Proteins and peptides of Amydae Carapax with molecular weight less than 6000 were proved to have biological activity. 8 components (Bj1-Bj8) were isolated from the active fraction. Bj4, Bj6 and Bj7 were screened as active components. Bj7 was further purified, resulting in 7 components (Bj701-Bj707). Bj704 and Bj707 showed significant biological activity. Mass spectrometry showed three molecular ion peaks with highest abundance, i.e. m/e 526, 542 and 572, i.e. m/e 526, 542 and 572, in Bj707 -A The amino acid sequences of above three peptide compounds were NDDY (Asn-Asp-Asp-Tyr), NPNPT (Asn-Pro-Asn-Pro-Thr), and HGRFG (His-Gly-Arg-Phe-Gly), respectively. And M572 was the most abandunt components., Conclusion: Three active peptide compounds of anti-hepatic fibrosis of Amydae Carapax were identified.

Dental pulp stem cells from teeth can be used for tooth regeneration. Although nondental stem cells derived from bone marrow can differentiate into odontoblast-like cells when recombined with embryonic oral epithelium, these cells can lose their ability to differentiate after an extended number of cell culture passages. There has been limited research to identify stem cells from other tissue sources to regenerate teeth. As another candidate source for mesenchymal stem cells, hair follicle has obtained much more attention recently because of its easy accessibility. In this study, cultured vibrissae follicle dermal papilla mesenchymal cells (FDPMCs) from adult C57BL/6 GFP mice can differentiate into adipocytes and osteoblasts in vitro. Moreover, in the inductive microenvironment generated by apical bud and dental mesenchyme from 7-day-old C57 mice, FDPMCs in vitro demonstrated odontogenic potential, as indicated by the morphological transformation, cell-cycle change and expression of tooth-specific markers. Under the same microenvironment, FDPMCs were incubated in vivo for 3 weeks. Coexpression of GFP and DSP proteins in the odontoblast layer was detected in the recovered implants, suggesting that GFP(+) FDPMCs can function as odontoblasts in vivo. Together, our data indicate for the first time that whisker FDPMCs from adult mice can differentiate to odontoblast-like cells.

Objective: To explore the clinical strategies for the screening of newborn eye diseases and obtain information concerning the incidence of newborn ocular diseases., Methods: Newborns in a baby-friendly nursery were evaluated for mass screening of eye diseases 2 to 7 days after birth (including reaction to light stimulation, external ocular examination and test for pupil red reflex) and those with abnormalities were subjected to diagnostic examination (external ocular examination with a hand-held slit-lamp, pupil red reflex and mydriatic examination). Newborns in neonatal intensive care unit (NICU) were subjected to screening 5 to 14 days after birth and then, together with those with high risk factors, received a comprehensive examination for screening and diagnostic purposes. The suspected cases were referred to department of ophthalmology for definite diagnosis., Results: Among the 15,398 (91.65%) newborns who were enrolled the screening program, 12 different eye diseases (involving 1266 cases) were detected, with a prevalence of 8.22%. Of these eye diseases, 7 were congenital ocular diseases, involving 809 cases (5. 254%) and including congenital ptosis in 2 cases (0.013%), congenital corneal opacity in 6 cases (0.039%), persistent pupillary membrane in 724 cases (4.702%), congenital cataract in 15 cases (0.097%), persistent hyaloid artery in 54 cases (0.351%), obstruction of nasolacrimal duct in 7 cases (0.046%) and lacrimal gland prolapse in 1 cases (0.007%). Five different diseases (457 cases, 2. 968%) detected were acquired in nature, including neonatal conjunctivitis in 391 case (2.539%), vitreous hemorrhage in 6 cases (0.039%), retinal hemorrhage in 34 cases (0.221%), and neonatal dacryocystitis in 23 cases (0.149%). Of 27 premature babies with body weight lower than 1500 g, 3 had retinopathy of prematurity (ROP, 6 eyes involved)., Conclusions: Early intervention is of great importance for the prevention and treatment of neonatal ocular diseases. The screening of newborn ocular diseases is not only feasible but also effective in the monitoring and control of the eye diseases in neonates.

Objective: To explore the multi-differentiated capability of human dental pulp stem cells (hDPSCs) obtained by cell-clone culture approach and to determine the appropriate induced medium., Methods: The cloned isolation and expansion of hDPSCs were preinduced for 24 h, and were subsequently replaced with neural-inductive medium containing certain concentration of dimethylsulfoxide (DMSO), butylated hydroxyanisode (BHA), forskolin, P-mercaptoethanol (p-ME) and hydrocortisone for 4 days. Then induced cells were analyzed by morphological observation, immnocytochemical staining for non-specific esterase (NSE) and glial fibrillary acidic protein (GFAP) expression, RT-PCR for GFAP mRNA. Meanwhile, the uninduced hDPSCs were used as negative control., Results: The morphology of induced cells changed at the initial 12 h, and displayed a typical neuron-like cells at 24 h. There was a gradual increase in the number of these neuronal differentiated cells with continuous induction. Furthermore, immnocytochemical staining showed that the induced cell expressed NSE and GFAP, two marked enzymes of neuron cell. The GFAP mRNA was also detected in induced cells by RT-PCR assay. In contrast, the uninduced cells maintained its original appearance and had no expression on them., Conclusion: hDPSCs may possess potential of multiple-differentiation and may differentiate into neuron-like cells on certain inductive condition.

Objective: To explore the model and the feasibility of newborn hearing and ocular disease simultaneous screening program and to study the birth prevalence of newborn hearing loss and newborn ocular diseases., Methods: The universal newborn hearing screening (UNHS) was performed using transient otoacoustic emission (TEOAE) in well baby nursery and by a two-stage TEOAE and auto auditory brainstem response (AABR) protocol in neonatal intensive care unit (NICU). The UNHS was simultaneous done with newborn ocular disease screening program. The examination technical method was following: the response to light, external inspection of the eyes and lids, pupil examination, red reflex examination, funduscope examination after pupil dilation for referral (for all newborn in NICU). The infants who were referred by two-stage hearing screening and/or had high-risk factors of hearing loss received following-up and routine audiological evaluation and personalized intervention from 6 months to 3 years of age. The cases had positive sign and (or) abnormal results of the ocular disease screening were referred for further examination by pediatric ophthalmologists., Results: A total of 16 800 children born in Jinan Maternal and Child Hospital from October 1, 2002 to April 30, 2005. Of these infants, 15 398 cases (91.7%) had access to the simultaneous screening program for hearing and ocular diseases. The incidence of congenital sensorineural hearing loss (SNHL) among infants who did UNHS was 0.312% (48/15 398) in bilateral and 0.227% (35/15 398) in unilateral; Of the 4 cases of congenital SNHL complicated with newborn ocular diseases: 1 profound SNHL (bilateral), auditory neuropathy with congenital cataract (bilateral), 1 mild SNHL (bilateral) with membrana papillaris perseverance (left) and 1 mild SNHL (bilateral) with retina vein dilatation (bilateral), 1 mild SNHL (right) with persistent hyaloid artery (bilateral). In all 15 398 newborns, 15 neonates with congenital cataract were detected (22 eyes, 0.10%). Twenty seven neonates with less than 1500 g birth weight admitted to NICU, retinopathy of prematurity was detected in 3 neonates (6 eyes)., Conclusion: Hearing loss and ocular diseases was not rare in neonatal and infancy. Newborn hearing and ocular disease simultaneous screening program was not only feasible but also effective in detecting hearing loss and (or) ocular disorders. Early intervention was important for the prevention or treatment of neonatal hearing loss and (or) ocular diseases, such as newborn hearing loss with congenital cataract, retinopathy of prematurity and so on.

Objective: To search the DNA sequences specific to virulent strain of Streptococcus mutans in the public database and explore new genes or new functions of already known genes from Streptococcus mutans of serotype c and suppose their functions., Methods: Thirty-one DNA fragments unique to virulent strain of Streptococcus mutans were sequenced. The sequences of these presumptive virulence DNA fragments were subjected to search through software BLASTn and BLASTx in public database, and their putative biological functions were analyzed. RESULTS Two clones were picked repeatedly. The size of the remaining DNA fragments ranged from 113 bp to 776 bp. The average G+C content was 38.59%, similar to that of the gene-coding sequences in Streptococcus mutans strain UA159 whose genome sequences were just complete. Of the twenty-nine DNA fragments, five potentially represented new DNA fragments in Streptococcus mutans, thus registered and obtained their gene's accession number in GenBank. The remaining DNA fragments showed high homology to known genes of Streptococcus mutans strain UA159. Their predicted functions of these fragments were associated to bacterial signal transduction, transcriptional regulation, stress-damage repair, biochemical metabolism, outer membrane protein synthesis, adhesion on tooth surface and hypothetical proteins., Conclusion: The gene analysis, identification and functional forecasting were carried out through bioinformatics associated software and database to find out new genes and new functions of known genes, and to supply the groundwork for researches in gene functions.

Streptococcus mutans is generally considered to be the principal aetiological agent for dental caries. Phenotypic variation in strains is often associated with differences in gene content, so the isolation of DNA fragments from these genes or associated regions is illuminating. The S. mutans strains 9-1 and 9-2, which both colonized the same oral cavity, were selected after screening for the possession of suspected virulence traits. Genomic DNA of strain 9-1 was used as the tester, and that of 9-2 was used as the driver. Suppression subtractive hybridization (SSH) was applied between the tester and the driver DNAs. The subtractive products were cloned into a pCR2.1 vector. Clone libraries representing sequence differences were obtained. The subtractive fragments that were found specifically in strain 9-1 but not in strain 9-2 were identified by dot blotting and then sequenced. BLASTn and BLASTx sequence homology analyses were subsequently performed. Twenty-seven sequences were found in the genome of strain 9-1 that were not in 9-2. Among them, three revealed no homology to published nucleotide sequences while the remaining sequences showed 81-100% homology to known genes of S. mutans strain UA159. These sequences are involved in competence development, signal transduction and transcriptional regulation, repairing stress damage, transport, carbohydrate catabolism, biochemical synthesis, or unknown functions. Differences exist in the genomes of different S. mutans isolates. SSH is effective in screening for S. mutans strain specific DNA sequences.

It has been generally proved impossible to reassemble ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) from fully denatured subunits in vitro in higher plant, because large subunit of fully denatured Rubisco is liable to precipitate when the denaturant is removed by common methods of direct dilution and one-step dialysis. In our experiment, the problem of precipitation was resolved by an improved gradual dialysis method, which gradually decreased the concentration of denaturant. However, fully denatured Rubisco subunits still could not be reassembled into holoenzyme using gradual dialysis unless chaperonin 60 was added. The restored activity of reassembled Rubisco was approximately 8% of natural enzyme. The quantity of reassembled Rubisco increased greatly when heat shock protein 70 was present in the reassembly process. ATP and Mg2+ were unnecessary for in vitro reassembly of Rubisco, and Mg2+ inhibited the reassembly process. The reassembly was weakened when ATP, Mg2+ and K+ existed together in the reassembly process.

We isolated dental papilla mesenchymal cells (DPMCs) from different rat incisor germs at the late bell stage and incubated them as cell pellets in polypropylene tubes. In vitro pellet culture of DPMCs presented several crucial characteristics of odontoblasts, as indicated by accelerated mineralization, positive immunostaining for dentin sialophosphoprotein and dentin matrix protein 1, and expression of dentin sialophosphoprotein mRNA. The allotransplantation of these pellets into renal capsules was also performed. Despite the absence of dental epithelial components, dissociated DPMCs with a complete loss of positional information rapidly underwent dentinogenesis and morphogenesis, and formed a cusp-like dentin-pulp complex containing distinctive odontoblasts, predentin, dentin, and dentinal tubules. These results imply that DPMCs at the late bell stage can reexhibit the dental morphogenesis and dentinogenesis by themselves, and epithelial-mesenchymal interactions at this stage may not be indispensable. Furthermore, different DPMC populations from the similar stage may keep the same developmental pattern.

Objective: To construct a suppression subtractive library of virulence-related genes from c serotype Streptococcus mutans (S. mutans), and lay foundations for screening the virulent genes., Methods: After being isolated from virulent and avirulent strain of S. mutans respectively, the intact and high-pure genomic DNA was digested with three appropriate four-base-cutting restriction endonueleases to produce fragments of optimal length. The digested DNA of the virulent strain ligated with adaptor was used as tester DNA, and that of the avirulent strain as driver DNA. Then the suppression subtractive hybridization was carried out, and the efficiency of ligation and subtraction detected respectively. The subtracted fragments were inserted into vector pCR2. 1 using T/A cloning kit, and transformed into E. coli TOP10F' competent cells. Those white colonies were selected to construct the suppression subtractive library., Results: Alu I chosen from three restriction endonucleases was verified to be suitable for preparing restriction fragments from S. mutans genomic DNA. Through electrophoresis of Alu I -digested DNA, a smear ranged from 0.1 to 2.0 kb was observed. The ligation efficiency of tester DNA with adaptor was at least higher than 25 percent. The subtraction efficiency of suppression subtractive hybridization confirmed the success in enrichment of differential genes between virulent and avirulent strain of S. mutans. In the subtracted group, the appearance time of the 23S rRNA gene both in tester and driver DNA was later than that in the unsubtracted group by six cycles. It suggested that suppression subtractive hybridization happened indeed. After the subtracted fragments were cloned, 96 colonies were picked up for constructing the suppression subtractive library of virulence-related genes of S. mutans., Conclusion: Suppression subtractive hybridization allows rapid and easy construction of virulence-related gene library of S. mutans.

Objective: To establish three-dimensional culture model of human dental mesenchymal cells and bioengineer in vivo with ceramic bovine bone (CBB) and Collagraft as scaffolds., Methods: Human dental mesenchymal cells induced upon stimulation of bFGF and IGF-1 or TGF-beta(1) were implanted onto CBB and Collagraft containing the same kinds of growth factors respectively. Then cell/scaffold constructs were transplanted into nude mice to establish in vivo culture model of dental mesenchymal cells. Control groups were set up at the same time. After 4 weeks or 10 weeks, the implants were taken out for histological and immunohistochemical analysis., Results: Within 10-week implant tissues, typical dentin-pulp complex-like structures were generated in scaffolds containing growth factors. Human dentin sialoprotein (DSP) was expressed in the newly formed dentin. This phenomenon wasn't observed in control groups and 4-week implants., Conclusions: Dentin-pulp complex-like structures could be bioengineered successfully with human dental mesenchymal cells and CBB or Collagrafts containing growth factors in nude mice.

Purpose: To investigate IRF6 gene mutation in a van Der Woude syndrome (VWS) family in Henan province., Methods: PCR and DNA sequencing was employed to detect the mutation of IRF6.Secondary construction transformation analysis was performed using PIX-Protein Identification software., Results: A CGC>TGC(r.279c-->t) transversion of IRF6 was identified in condon 6, showing complete segregation with the disease phenotypes and was resulting in changes of the secondary constructure of IRF6., Conclusion: VWS is caused by mutations in IRF6 gene, and IRF6 is closely related to the development of lip, palate and tooth.

Objective: To investigate the effect of transforming growth factor beta (TGF-beta) on ectomesenchymal stem cells differentiating to smooth muscle cells., Methods: 60 pmol/L TGF-beta was added to the ectomesenchymal stem cells of embryonic facial processes. Immunohistochemistry assay and image analysis were used to value the expression extent of a smooth muscle actin (alpha-SMA) and quantitative RT-PCR was used to value the quantity of alpha-SMA., Results: 2 days later, about 95% cells in TGF-beta group and 65% cells in control group without differentiation inhibitor expressed alpha-SMA. Expression of alpha-SMA in TGF-beta group was stronger than that of control group after one and two days. Quantitative RT-PCR showed the quantity of alpha-SMA mRNA in treated group cells was more than that of in control group., Conclusion: Quantity of alpha-SMA in TGF-beta group is more than that of spontaneous differentiation group. TGF-beta has positive effect on ectomesenchymal stem cells differentiating to smooth muscle cells.

Cranial neural crest-derived ectomesenchymal cells may be pluripotent stem cells that are capable of generating a range of phenotypes. The fate of these cells appears to be determined in part by intrinsic genetic programs and also by the influence of extracellular signals in the local environment. The extent of lineage determination once neural crest cells have migrated to the first branchial arch is not clear, although branchial arch pattern is not thought to be the result of crest predetermination. The aim of the present study was to test the hypothesis that ectomesenchymal cells of the first branchial arch show properties of pluripotent stem cells, the lineage of which may be directed by specific molecular signaling. Ectomesenchymal cells were enzymatically isolated from the mandibular processes of BALB/c mice and maintained in an undifferentiated state while cultured with leukemia inhibitory factor or induced to differentiate by lineage-specific induction factors or growth conditions, including transforming growth factor beta, forskolin, and a mineralization-promoting medium. Morphological observations and immunocytochemistry demonstrated that cells could be induced to differentiate into smooth muscle cells, glial cells, and osteoblasts, respectively. In the presence of the mineralization-promoting medium, alkaline phosphatase activity increased significantly and mineralization nodules formed. The data reported support the concept that many, although not all, first branchial arch-derived ectomesenchymal cells show properties of multipotent stem cells, the subsequent fate of which can be influenced by induction factors and growth conditions. Some cells, however, showed a degree of commitment with respect to their fate. The possible application of first branchial arch-derived stem cells to tissue engineering of the orofacial tissues should involve consideration of the developmental stage of cell harvesting and the desired cell fate.

Objective: To explore the feasibility of applying flash visual evoked potentials (FVEPs) for visual function test newborns and infants and bring out the consultable laboratory values of FVEPs. The technology of FVEP could be used as diagnostic tests for those who failed the screening and the infants who were cared for in the NICU., Methods: 41 normal neonates (

Objective: To investigate the characteristic and phenotype of ectomesenchymal stem cells of human fetal facial processes and the procedure of spontaneous differentiation to smooth muscle cells., Methods: The primary ectomesenchymal cells of E 50 human fetal facial processes were isolated by 2.5 g/L trypsin and cultured with DMEM/F 12 with 10(-6) U/L leukemia inhibitor factor(LIF). The morphology and growth rate were observed by inverted microscop. After being withdrawn LIF, the characteristic of cells were identified by immunohistochemistry and RT-PCR. Ultrastructure was observed by transmission electron microscope., Results: The cultured cells displayed monolayer growth and were fibroblast-like with 2-4 processes. The cells were stainely positived for anti-human natural killer cell marker-1, Vimentin, S-100, neuron specific enolase, myoglobin and VIII factor, but negatively for glial fibrillary acidic protein, neural fiblament, alpha-SMA and cytokeratin in immunohistochemistry. Two days after being withdrawn the LIF, cells expressed alpha-SMA in protein and mRNA levels. The cells were rich in muscular filament-like structure and dense bodies under transmission electron microscope., Conclusion: Cultured cells are undifferentiated ectomesenchymal stem cells. The cells have the potential for differentiating spontaneously to smooth muscle cell.