[The characteristics of plasma lipids in silicosis rat models were studied based on lipid metabolomics].

Objective: To screen the differential metabolites and metabolic pathways in silicosis model by analyzing plasma metabolomics of silicosis rats. Methods: In May 2021, twenty male SD rats were randomly divided into control group (C), 1-week silicosis group (S1W), 2-week silicosis group (S2W) and 4-week silicosis group (S4W), with 5 rats in each group. Rats were intratracheally instillated with 1ml crystalline SiO(2) suspension (50 mg/ml) or normal saline and were sacrificed after 1 week, 2 weeks and 4 weeks, HE staining was used to observe the lung pathology of rats. The plasma samples were analyzed by UPLC-IMS-QTOF mass spectrometer to screen out potential differential metabolites in silicosis models and analyze their lipid enrichment. Results: HE results showed that nodules formed in the silicosis model group, and with the extension of time, nodules gradually increased and alveolar structure was gradually destroyed. Metabolomics screened out 14 differential metabolites in S1W, 24 in S2W, and 28 in S4W, and found that the differential metabolites were mainly enriched in the metabolism of glycerophospholipid metabolism, fatty acid degradation, Glycosylphosphatidylinositol (GPI) -anchor biosynthesis, fatty acid elongation and other metabolic pathways. Conclusion: There are significant changes in plasma lipid metabolites in silicosis rat models.

[Efficacy of decitabine combined with low dose chemotherapy on children with acute myeloid leukemia].

Objective: To evaluate the efficacy of decitabine combined with low dose chemotherapy (LDC) in the treatment of high-risk, refractory and relapsed pediatric acute myeloid leukemia (AML). Methods: Clinical data of 19 AML children treated with decitabine combined with LDC in the Department of Hematology, Children's Hospital of Soochow University from April 2017 to November 2019 were analyzed retrospectively. The therapeutic response, adverse effects and survival status were analyzed,and the outcomes of patients were followed up. Results: Among 19 AML cases, there were 10 males and 9 females. Five cases were high-risk AML, 7 cases were refractory AML, and 7 cases were relapsed AML. After one course of decitabine+LDC treatment, 15 cases achieved complete remission, 3 cases got partial remission, and only 1 case didn't get remission. All patients received allogeneic hematopoietic stem cell transplantation as consolidation therapy. The follow-up time of all cases was 46 (37, 58) months, 14 children had survived. The cumulative three-year overall survival rate was (79±9) %, events free survival rates was (68±11) %, and recurrence free survival rate was (81±10) %. The most common adverse effects related to the induction treatment were cytopenia (19 cases) and infection (16 cases).There were no treatment-related death during the therapy. Conclusion: Decitabine combined with LDC is a safe and effective option for high-risk, refractory and relapsed AML children, which provides an opportunity for HSCT.

[Research progress on the treatment of presbyopia].

Presbyopia is a physiological aging situation that the plasticity and elasticity of the lens and the function of the ciliary muscle become weaker, resulting in a decreased accommodation and inability to focus on near objects. Nowadays, there are many clinical strategies to correct presbyopia, each of which has its own advantages and disadvantages, however, there is no true sense of way to restore accommodation function. This article reviews both worldwide and domestic research on presbyopia, and analyzes and summaries the status quo as well as research progress of presbyopia correction modalities, surgical approaches, and drug therapies, hoping to provide a reference for clinical works.

[Treatment of adult-acquired buried penis with suprapubic liposuction combined with modified Devine operation].

OBJECTIVE: To evaluate the safety and efficacy of suprapubic liposuction combined with modified Devine surgery in adult patients with concealed penis caused by obesity. METHODS: The clinical data of 26 adult patients with buried penis admitted to the Department of Urology of Peking University People' s Hospital and the Department of Surgery of Beijing Eden Hospital from September 2017 to June 2020 were analyzed retrospectively. The average age of the patients was (33.0 ± 5.7) years, the average body mass index (BMI) was (29.0±5.4) kg/m2, and the penis length in the supine position was (2.9±1.3) cm. All the patients were treated with suprapubic liposuction combined with modified Devine operation. The improvement of penis length and complications were statistically analyzed after operation, and the satisfaction of the patients was followed up, 1 = dissatisfied; 2 = basically satisfied; 3 = satisfied; 4 = very satisfied. The measurement data were expressed in (mean±SD), nonparametric Friedman tests and multiplex analysis methods were used for data comparison. RESULTS: The average liposuction volume of the 26 patients was (450.0±90.2) mL. Immediately after operation: the penis length was (7.4±2.1) cm, increased by (4.5±1.6) cm compared with that before operation; three months after operation: the penis length was (5.3±1.8) cm, increased by (2.4±0.7) cm compared with that before operation. There was significant difference in penis length before operation, immediately after operation and three months after operation (P < 0.01). All the patients had no sexual intercourse disorder or dysuria. Postoperative edema occurred in 11 cases (42.3%), ecchymosis in 7 cases (26.9%), poor healing of prepuce wound in 2 cases (7.8%), hematoma in 1 case (3.8%), 5 cases (19.2%) without postoperative complications, and no patient had wound infection. Seventeen patients (65.4%) were very satisfied with the appearance and function of the penis, 6 patients (23.1%) were satisfied, 3 patients (11.5%) were basically satisfied, and no patients were dissatisfied. The average score of all the patients' satisfaction with postoperative penis appearance and function was (3.5±0.7). CONCLUSION: Suprapubic liposuction combined with modified Devine operation is safe and effective in the treatment of adult-acquired buried penis.

Evaluation of the Efficacy of Three Direct Fed Microbial Cocktails To Reduce Fecal Shedding of Escherichia coli O157:H7 in Naturally Colonized Cattle and Fecal Shedding and Peripheral Lymph Node Carriage of Salmonella in Experimentally Infected Cattle.

Two experiments were conducted to evaluate the feeding of direct fed microbials (DFMs) on fecal shedding of Escherichia coli O157:H7 in naturally infected cattle (experiment I) and on Salmonella in the feces and peripheral lymph nodes (PLNs) of experimentally infected cattle (experiment II). Thirty cattle, 10 per treatment, were used in each experiment. Treatments in experiment I consisted of a control (lactose carrier only); DFM1, a 1:1 ratio of Enterococcus faecium and Lactobacillus animalis; and DFM2, a 1:1 ratio of Lactobacillus acidophilus and Pediococcus acidilactici. In Experiment II, DFM1 was replaced with DFM3, a 1:2 ratio of Lactobacillus reuteri and other Lactobacillus strains. Additives were mixed in water and applied as a top-dressing to each pen's daily ration for 50 days. Approximately half-way through each experiment, the DFM concentration was doubled for the remainder of the study. Fecal samples were collected throughout experiment I and cultured for E. coli O157:H7. Cattle in experiment II were inoculated intradermally with Salmonella Montevideo on days 32, 37, and 42 and then necropsied on days 49 and 50 (five cattle per treatment on each day). Innate immune function was assessed on days 29, 49, and 50. In experiment I, fecal concentration and prevalence of E. coli O157:H7 were not different (P > 0.10) nor was there an effect (P = 0.95) on the percentage of super shedders (cattle shedding ≥3.0 log CFU/g of feces). In experiment II, no treatment differences (P > 0.05) were observed for Salmonella in the PLNs except for the inguinal nodes, which had a significantly lower Salmonella prevalence in DFM-supplemented cattle than in the controls. Immune function, as measured by monocyte nitric oxide production and neutrophil oxidative burst, was decreased (P < 0.05) in the DFM treatment groups. Although results of this research indicate little to no effect of these DFMs on E. coli O157:H7 or Salmonella in cattle, an increase in the duration of administration to that similar to what is used for commercial cattle might elicit treatment differences.

[Expression of cytokeratin(CK)7, CK8/18, CK19 and p40 in esophageal squamous cell carcinoma and their correlation with prognosis].

Objective: To evaluate the expression of cytokeratin (CK)7, CK8/18, CK19 and p40 in esophageal squamous cell carcinoma (ESCC) and its significances. Methods: One hundred and ninety cases of surgically resected ESCCs and 154 normal esophageal tissues as control were collected at the First Affiliated Hospital of Zhengzhou University in 2012.Of the 190 ESCC cases including 116 male and 74 female, aged 28-82 (60.3±8.6) years, 88 cases <60 years old and 102 cases ≥60 years old. Tissue sections were immunostained for CK7, CK8/18, CK19 and p40, and the expression was evaluated and correlated with the clinicopathologic findings and outcome. Results: CK19 and p40 were expressed in 190 cases of ESCCs; with 147 cases (77.4%) and 151 cases (79.5%) showing high p40 and CK19 expression, respectively; while 43 cases (22.6%) and 39 cases (20.5%) showed low p40 and CK19 expression, respectively. The low expression groups showed more lymph node metastases and higher pTNM stages compared to the high expression groups. The high CK19 expression group showed better prognosis than the low expression group (P<0.01); p40 expression was not correlated with prognosis(P>0.05). In contrast, CK7 and CK8/18 expression was only seen in 29 cases (15.3%) and 59 cases (31.1%) of ESCCs, respectively, and their expression correlated significantly with the degree of tumor differentiation and lymph node metastasis (P<0.05). The prognosis in the CK7 negative group was better than that in the CK7 positive group. Similar results were found in CK8/18 expression. Multivariate analysis revealed that pTNM stages, low CK19 expression and CK8/18 expression were independent prognostic factors. Conclusions: Low p40 expression and the expression of CK7 and CK8/18 cannot exclude poorly-differentiated ESCCs.CK7 and CK8/18 expression and low CK19 and p40 expression in the ESCCs are associated with lymph node metastasis and poor prognosis. Decreased expression of CK19 and positive expression of CK8/18 in ESCCs are independent prognostic markers.

[Research on the causes of death associated with combined effects of HBV and HCV infection in patients with acquired immunodeficiency syndrome].

Objective: To investigate the combined effects of hepatitis B virus and hepatitis C virus (HBV/HCV) infection on the cause of death in patients with acquired immunodeficiency syndrome (AIDS). Methods: The causes of death of 111 cases of AIDS with HBV/HCV (combined infection group) and 210 AIDS patients (single infection group) admitted to our hospital from 2012 to 2016 data were compared using chi-square test. Results: There was no statistically significant difference in gender composition and age in the combined infection groups (P > 0.05). The main causes of death in the combined infection group were severe pneumonia (44.1%), end-stage liver disease (18.9%), and central nervous system infection (14.4%). The main causes of death in the single infection group were severe pneumonia (47.6%) and central nervous system infection (14.3%) and tumor (13.3%). There was no case of end-stage liver disease. The ratio of end-stage liver disease in the former group was significantly higher than that in the latter group (χ(2) = 42.511, P < 0.001). The main cause of death in 12 HIV/HBV/HCV triple-infected patients was end-stage liver disease, accounting for 41.7%, which was significantly higher than 18.9% of end-stage liver disease in HIV/HBV or HIV/HCV dual infection (99 cases). And the difference was statistically significant (χ(2) = 4.539, P = 0.033); however, the ratio of end-stage liver disease in 50 HIV/HBV co-infected patients and 49 HIV/HCV co-infected patients was 16.0% vs. 16.3%, respectively, and the difference was not statistically significant (χ(2) = 0.002, P = 0.965). In the co-infected group, 36 patients had CD4(+) cell counts >100/µl, the primary cause of death was end-stage liver disease, accounting for 38.2%. 75 patients with CD4(+) ≤ 100/µl died due to end-stage liver disease, accounting for 9.3% and the difference was statistically significant (χ(2) = 13.852, P < 0.05). Conclusion: End-stage liver disease is the main cause of death in patients with AIDS combined with HBV or HCV, especially triplet infection and CD4(+) cell count > 100/µl. An early diagnosis and treatment of HBV or HCV infection should commence as soon as possible.

A prospective evaluation of minimal residual disease as risk stratification for CCLG-ALL-2008 treatment protocol in pediatric B precursor acute lymphoblastic leukemia.

OBJECTIVE: The aim of this prospective study was to evaluate the cut-off value of minimal residual disease (MRD) in predicting the efficacy of CCLG-ALL-2008 or CCLG-2008 treatment protocol on pediatric B-precursor ALL (BP-ALL). PATIENTS AND METHODS: Three hundred and seventy-nine Chinese pediatric BP-ALL were enrolled in this study between Dec 2008 and Sep 2013 in two stratified cohorts. One hundred and fifty-three patients enrolled between Dec 2008 and Oct 2010 as the first cohort, and 196 patients enrolled from Nov 2010 to Sep 2013 as the second cohort. Clinical and biological characteristics and 5 years EFS, RFS, and OS were analyzed. RESULTS: Patients with E2A-PBX1 showed a favorable treatment response with a lower minimal residual disease (MRD) level (< 10-4) at the time point 1 (TP1, p = 0.039) and the highest proportion of the 5-year EFS, RFS, and OS. A high level of MRD was associated with high WBC counts, increased age, BCR-ABL1 fusion gene, MLL rearrangements and adverse karyotypes. In comparison with the first cohort, the second cohort with the MRD assay incorporated prospectively, the standard risk (SR) and the intermediate risk (IR) patients showed a better RFS, EFS, and OS while the high-risk (HR) patients displayed worse RFS, EFS, and OS than those of the first cohort, respectively. Patients with MRD level at either 10-4 or 10-3 showed a similar OS at TP1 or TP2, and patients with MRD level above 10-2 had the worst OS. CONCLUSIONS: This study indicated that the levels of MRD to be an adequate guide in risk-adapted treatment under the CCLG-ALL-2008 protocol and can be adapted to the future development of advanced clinical protocols.

In Vitro Effects of Thymol-ß-D-Glucopyranoside on Salmonella enterica Serovar Typhimurium and Escherichia coli K88.

Although thymol is bactericidal against many pathogens in vitro, its in vivo effectiveness against pathogens in the lower gastrointestinal tract is limited because of its rapid absorption in the proximal gut. Thymol-ß-D-glucopyranoside (ß-thymol), a conjugated form of thymol, can deliver thymol to the lower gastrointestinal tract and has shown antibacterial effects. In the present study, we examined the in vitro effects of ß-thymol on Salmonella enterica serovar Typhimurium (ST) and Escherichia coli K88 (K88). We inoculated one-half strength Mueller-Hinton broth with 5.8 ± 0.09 log CFU/ml novobiocin- and naladixic acid-resistant (NN) ST (NVSL 95-1776) and 5.1 ± 0.09 log CFU ml(-1) NN-resistant K88, with or without porcine feces (0.1% [wt/vol]) (fecal incubations). The resultant bacterial suspensions were distributed under N2 to triplicate sets of tubes to achieve initial concentrations of 0, 3, 6, and 12 mM for ST treatments and 0, 3, 12, and 30 mM for K88 treatments. Samples were incubated at 39°C and then plated onto NN-containing brilliant green agar and NN-containing MacConkey agar; ST and K88 CFU concentrations were determined via 10-fold dilutions, and viable cell counts were performed at 0, 6, and 24 h. No differences in ST CFU counts were observed in ß-thymol-treated tubes without the added porcine feces (i.e., pure culture) at 6 or 24 h. However, in tubes that contained fecal incubations, ST CFU counts were reduced (P < 0.05) from controls at 6 h in tubes treated with 6 and 12 mM ß-thymol, whereas in tubes treated with 3, 6, and 12 mM ß-thymol the CFU counts were reduced (P < 0.05) at 24 h. No differences were observed in K88 CFU counts in pure culture or in fecal incubations at 6 h, but K88 CFU counts were reduced (P < 0.05) in both pure and fecal incubations at 24 h. The results from this study demonstrate that ß-thymol, in the presence of fecal suspensions, has anti-Salmonella and anti-E. coli effects, suggesting a role of ß-glycoside-hydrolyzing microbes for the release of bactericidal thymol from ß-thymol.

Overexpressed miR-155 is associated with initial presentation and poor outcome in Chinese pediatric acute myeloid leukemia.

OBJECTIVE: Acute myeloid leukemia (AML) is the second leading leukemia in children. There is growing evidence that microRNAs (miRNAs) are crucial regulators involved in leukemogenesis. This study aimed to investigate the role of miR-155 in Chinese pediatric AML by evaluating its diagnostic and prognostic significance. PATIENTS AND METHODS: The expression of miR-155 and miR-25 in bone marrow specimens from 83 AML and 29 non-malignancies children were analyzed by TaqMan probe-based real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). RESULTS: The expression level of miR-155 was significantly higher in AML patients than in controls. Besides, a lowest miR-155 level was found in favorable prognosis group and t (15; 17)/M3 subgroup compared to the rest, while a higher level in C-Kit/FLT3-ITD mutation and relatively lower level existed in "Negative" mutation group. Moreover, miR-155 level was positively associated with the white blood cell (WBC) count, serum lactate dehydrogenase (LDH) and C-reaction protein (CRP) value in peripheral blood (PB), as well as miR-25/miR-196b expression levels. Survival analysis showed a statistically negative association with overall survival (OS) in the expression of miR-155 in chemotherapy group. CONCLUSIONS: These finding suggested that miR-155 expression cannot only be promising biomarker for the early detection of pediatric AML but also predict poor outcome. MiR-155 would be a novel biomarker for diagnosis, prognosis and therapy in pediatric AML.

Whole exome sequencing implicates PTCH1 and COL17A1 genes in ossification of the posterior longitudinal ligament of the cervical spine in Chinese patients.

Ossification of the posterior longitudinal ligament (OPLL) of the cervical spine is a complex multifactorial disease. Patients with OPLL commonly present with symptoms in their 40s or 50s. The genetic basis of OPLL remains poorly understood. Exome capture combined with massively parallel DNA sequencing has been proposed as an efficient strategy to search for disease-causing genes of both monogenic and multigenic disorders. To identify candidate pathogenic genes associated with OPLL, we performed whole exome sequencing (WES) on two unrelated southern Chinese OPLL patients. The entire DNA coding region of the candidate genes was amplified by PCR and Sanger sequenced. The common single nucleotide polymorphisms were analyzed by association studies. WES revealed p.T265S/PTCH1, p.P1232L/PTCH1, and p.T902S/COL17A1 mutants in the two female cases with mixed OPLL. These were confirmed by Sanger sequencing. p.P1232L/PTCH1, p.N1374D/COL17A1 and p.T902S/COL17A1 were subsequently identified in three males with continuous OPLL and one female with mixed OPLL. The association studies indicated that the SNPs rs805698 and rs4918079 in COL17A1 were significantly associated with OPLL. This study suggests that WES may be a practical approach to revealing significant genetic involvement in OPLL. Variants of the PTCH1 and COL17A1 genes may contribute to the development of OPLL.

Molecular cloning and expression analysis of the ethylene insensitive3 (EIN3) gene in cucumber (Cucumis sativus).

The plant gaseous hormone ethylene regulates many aspects of plant growth, development, and responses to the environment. Ethylene insensitive3 (EIN3) is a key transcription factor involved in the ethylene signal transduction pathway. To gain a better understanding of this particular pathway in cucumber, the full-length cDNA encoding EIN3 (designated as CsEIN3) was cloned from cucumber for the first time by rapid amplification of cDNA ends. The full length of CsEIN3 was 2560 bp, with an open reading frame of 1908 bp encoding 635 amino acids. Sequence alignment and phylogenetic analyses revealed that CsEIN3 has high homology with other plant EIN3/EIL proteins that were derived from a common ancestor during evolution, and CsEIN3 was grouped into a cluster along with melon. Homology modeling demonstrated that CsEIN3 has a highly similar structure to the specific DNA-binding domain contained in EIN3/EIL proteins. Based on quantitative reverse transcription-polymerase chain reaction analysis, we found that CsEIN3 was constitutively expressed in all organs examined, and was increased during flower development and maturation in both male and female flowers. Our results suggest that CsEIN3 is involved in processes of flower development. In conclusion, this study will provide the basis for further study on the role of EIN3 in relevant biological processes of cucumber and on the molecular mechanism of the cucumber ethylene signaling pathway.

Study of chloropropanols in soy sauce by gas chromatography-triple quadrupole mass spectrometry with coupled column separation without derivatisation.

A qualitative and quantitative determination method for chloropropanols in soy sauce was developed by GC-MS/MS with coupled column separation without derivatisation. The target compounds were 1,3-dichloropropan-2-ol (1,3-DCP), 2,3-dichloropropan-1-ol (2,3-DCP), 3-monochloropropane-1,2-diol (3-MCPD) and 2-monochloropropane-1,3-diol (2-MCPD). 3-MCPD-d(5) was used as an isotope internal standard for MCPDs and 1,3-DCP-d(5) for DCPs. After spiking with internal standards and mixed with 1 g of Extrelut™ NT, about 1 g of the sample was washed by 4 ml of hexane and the analytes were eluted with 15 ml of 95% (v/v) ethyl ether/hexane mixture. The concentrated extract was directly injected without derivatisation, separated by a coupled column - a 3 m Innowax (polyethylene glycol) combined with a 30 m DB-5 ms ((5%-phenyl)-methylpolysiloxane) by a quartz capillary column connector - and detected by GC-MS/MS. The limits of detection (LODs) in the sample matrix were 1.0, 2.5, 5.0 and 5.0 µg kg(-1) for the above chloropropanols, respectively. The relative proportions of 2-MCPD/3-MCPD ranged from 0.19 to 3.74 in soy sauce samples. 2,3-DCP and 2-MCPD were more stable than 1,3-DCP and 3-MCPD under alkaline condition. The levels of chloropropanols can be decreased by an alkaline treatment process.

Plasma propofol concentrations during orthotopic liver transplantation.

OBJECTIVE: The aim of this study was to investigate the changes in plasma concentrations of propofol in three phases (the paleohepatic, anhepatic, and neohepatic phases) during orthotopic liver transplantation (OLT) using target-controlled infusion (TCI). METHODS: Ten patients undergoing OLT without venovenous bypass were studied (age 29-53 years, weight 56-79 kg). After intubation, a non-hypnotic target concentration of propofol 0.5 microg ml(-1) using a Diprifusor pump (Zeneca Pharmaceuticals, Macclesfield, UK) was administered as a supplement anesthesia throughout the procedure. Plasma samples were obtained in each phase for propofol assay, respectively. Performance parameters for the Diprifusor system in each phase, the percentage median performance error (MDPE), the percentage median absolute performance error (MDAPE), and the percentage median absolute constancy error (MDACE) were evaluated. RESULTS: In all patients, measured plasma propofol concentrations were several times higher than Diprifusor values in each phase during the procedure. In nine patients, propofol concentrations in the anhepatic phase were higher than those in the paleohepatic or neohepatic phase (P < 0.05). There were no significant differences between the paleohepatic and neohepatic phases. Interindividual variation of the plasma propofol concentrations was significant (P < 0.05). Percentage median performance error of Diprifusor in each phase, as well as MDAPE, was large (>300%) and was significantly higher in the anhepatic phase (P < 0.01), whereas MDACE was relatively small and there was no significant difference between phases. CONCLUSIONS: Models used by Diprifusor are not suitable for liver transplantation patients. A further study should be performed in order to determine all pharmacokinetic parameters of propofol in these patients.

Modeling gene expression with differential equations.

We propose a differential equation model for gene expression and provide two methods to construct the model from a set of temporal data. We model both transcription and translation by kinetic equations with feedback loops from translation products to transcription. Degradation of proteins and mRNAs is also incorporated. We study two methods to construct the model from experimental data: Minimum Weight Solutions to Linear Equations (MWSLE), which determines the regulation by solving under-determined linear equations, and Fourier Transform for Stable Systems (FTSS), which refines the model with cell cycle constraints. The results suggest that a minor set of temporal data may be sufficient to construct the model at the genome level. We also give a comprehensive discussion of other extended models: the RNA Model, the Protein Model, and the Time Delay Model.