Role of low-proportion, hydrophobic dissolved organic matter components in inhibiting methylmercury uptake by phytoplankton.

Uptake of methylmercury (MeHg), a potent neurotoxin, by phytoplankton is a major concern due to its role as the primary pathway for MeHg entry into aquatic food webs, thereby posing a significant risk to human health. While it is widely believed that the MeHg uptake by plankton is negatively correlated with the concentrations of dissolved organic matter (DOM) in the water, ongoing debates continue regarding the specific components of DOM that exerts the dominant influence on this process. In this study, we employed a widely-used resin fractionation approach to separate and classify DOM derived from algae (AOM) and natural rivers (NOM) into distinct components: strongly hydrophobic, weakly hydrophobic, and hydrophilic fractions. We conduct a comparative analysis of different DOM components using a combination of spectroscopy and mass spectrometry techniques, aiming to identify their impact on MeHg uptake by Microcystis elabens, a prevalent alga in freshwater environments. We found that the hydrophobic components had exhibited more pronounced spectral characteristics associated with the protein structures while protein-like compounds between hydrophobic and hydrophilic components displayed significant variations in both distributions and the values of m/z (mass-to-charge ratio) of the molecules. Regardless of DOM sources, the low-proportion hydrophobic components usually dominated inhibition of MeHg uptake by Microcystis elabens. Results inferred from the correlation analysis suggest that the uptake of MeHg by the phytoplankton was most strongly and negatively correlated with the presence of protein-like components. Our findings underscore the importance of considering the diverse impacts of different DOM fractions on inhibition of phytoplankton MeHg uptake. This information should be considered in future assessments and modeling endeavors aimed at understanding and predicting risks associated with aquatic Hg contamination.

Construction of ceRNA Network and Analysis of Key mRNA and Immune Function for Bladder Urothelial Carcinoma Based on Bioinformatics / 现代检验医学杂志

Objective To construct a regulatory network of competing endogenous RNA(ceRNA)with prognostic value for bladder urothelial carcinoma(BLCA),and analyze the relationship between key messenger RNA(mRNA)and immune function.Methods The UCSC Xena database was used to download mRNA expression data from 404 BLCA patients and 28 normal individuals and key mRNAs were screened by differential analysis.ENCORI database was utilized to search microRNAs(miRNAs)that bind to key mRNAs and all long non-coding RNAs(LncRNAs)that bind to miRNAs.The expression data of miRNA and LncRNA were downloaded from TCGA database,co-expression analysis was performed to identify key mRNA with all miRNAs and miRNA with all LncRNAs,and thus key miRNAs and LncRNAs were screened out.Survival analysis was conducted based on the differences in expression levels of these key mRNAs,miRNAs,and LncRNAs between tumor patients and normal individuals,and finally a ceRNA regulatory network was constructed.The correlation between key mRNAs and immune cells,immune checkpoints(CD274,PDCD1 and CTLA4),and immune cell marker genes(IG)was analyzed using the TIMER 2.0 database.Results A total of 22 key mRNAs were screened,with the most significant difference being proline 3-hydroxylase 4(P3H4).The expression of P3H4 in patients with BLCA was high,and survival time was shorter in patients with high expression.A sum of 33 miRNAs and 14 LncRNAs were screened using the key mRNAs as the central link.Through co-expression analysis and survival analysis,hsa-miR-151a-3p and MIR100 HG were identified as the key miRNA and key LncRNA with prognostic value.The differences in the above analysis results were statistically significant(all P＜0.05).Based on these findings,a ceRNA regulatory network consisting of 1 mRNA,1 miRNA,and 1 LncRNA was constructed.Immunoassay firstly revealed a significant positive correlation between double positive T cells and P3H4 expression in the tumor microenvironment of BLCA.Moreover,there were 3 types of immune cells(tumor-associated neutrophils,and tumor-associated macrophages,dendritic cells),3 immune checkpoints(CD274,PDCD1,CTLA4),and 15 IGs with significant correlation with P3H4.These differences were statistically significant(all P＜0.01).Conclusion This study could help to reveal the progression mechanism of BLCA.The constructed ceRNA network and immune analysis can offer new insights into potential biological targets and immunotherapy directions for the diagnosis,treatment,and prediction of BLCA patients.

Effects and mechnism of abnormal stress promoting MIF,COX2 and PGE2 in the progression of temporomandibular joint osteoarthritis / 解放军医学杂志

Objective To investigate the effects and mechnism of abnormal stress promoting macrophage mobility inhibitory factor(MIF),cyclooxygenase 2(COX2)and prostaglandin E2(PGE2)in the progression of temporomandibular joint osteoarthritis(TMJOA).Methods From January 2020 to December 2021,TMJOA and temporomandibular joint internal derangement(TMJID)patients(30 cases in each group,we divided the TMJOA into group TMJ Ⅰ,Ⅱ,Ⅲ according to the stage)who were admitted to TMJOA special clinic of the First Affiliated Hospital of Xinjiang Medical University and accompanied by abnormal occlusion were collected.The pain score of the occlusal state of the patients was evaluated by visual analogue scale.The expression levels of MIF,COX2 and PGE2 in synovial fluid were detected by ELISA.We used the unilateral anterior crossbite for TMJOA(UAC)rats model(the grouped into:UAC-4 weeks,UAC-8 weeks and UAC-12 weeks group),and control group at the same time(grouped into:Ctrl-4 weeks,Ctrl-8 weeks and Ctrl-12 weeks group),each group had 6 rats.The expression levels of MIF,COX2 and PGE2 in serum and synovial fluid of rats were detected by ELISA.The expression levels of IL-1β,IL-18,MIF,COX2 and PTGER2 in temporomandibular joint of rats were detected by Western blotting.The fluid flow shear stress(FFSS)model of fibroblast-like synovial cells(FLSs)was established,and the mRNA and protein expression levels of above indexes were detected by RT-PCR and Western blotting.Results Visual analogue scale evaluation showed that the pain score of TMJOA Ⅰ and Ⅱ group was significantly higher than that of TMJID(P<0.001).ELISA results showed that the expression levels of MIF,COX2 and PGE2 in synovial fluid in TMJOA group were higher than those in TMJID group(P<0.05),and the expression levels were the highest in TMJOA Ⅱ group.Compared with control group,the expressions of MIF,COX2 and PGE2 in serum and synovial fluid at UAC-4 weeks,8 weeks and 12 weeks were slightly higher,and significantly higher at UAC-8 weeks in rat TMJOA model(P<0.05).In addition,the expression trend of protein levels in temporomandibular joint tissues was similar,which showed higher expression levels of IL-1β,IL-18,MIF,COX2 and PTGER2(P<0.05).In the cell model where FFSS interfered with FLSs,with the increase of FFSS,cell with deformation,incomplete cell membrane and reduced number.Compared with control group,the expression levels of IL-1β,IL-18,MIF,COX2 and PGE2(PTGER2)of FLSs were increased in 1,3,5 and 10 dyn/cm2 intervention groups(P<0.05).Conclusion MIF,COX2 and PGE2 were highly expressed in temporomandibular joint synovial fluid of TMJOA patients with malocclusion.And these three factors were also highly expressed in serum and synovial fluid of UAC rats.The abnormal fluid shear stress promotes the secretion of MIF,COX2 and PGE2 by FLSs to participate in joint microenvironment inflammation and accelerate disease progression.

Imaging evaluation of cerebrospinal fluid otorrhea associated with inner ear malformation in children / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the imaging evaluation of cerebrospinal fluid (CSF) otorrhea associated with inner ear malformation (IEM) in children. Methods: The clinical data of 28 children with CSF otorrhea associated with IEM confirmed by surgical exploration in Beijing Children's Hospital, from Nov, 2016 to Jan, 2021, were analyzed retrospectively,including 16 boys and 12 girls, aged from 8-month to 15-year and 8-month old, with a median age of 4-year old. The shapes of stapes were observed during the exploration surgery, and the imaging features of temporal bone high resolution CT(HRCT) and inner ear MRI pre- and post-operation were analyzed. Results: In 28 children with CSF otorrhea, 89.3%(25/28) had stapes footplates defect during exploration. Preoperative CT showed indirect signs such as IEM, tympanic membrane bulging, soft tissue in the tympanum and mastoid cavity. IEM included four kinds: incomplete partition type I (IP-Ⅰ), common cavity (CC), incomplete partition type Ⅱ (IP-Ⅱ), and cochlear aplasia (CA); 100%(28/28) presented with vestibule dilation; 85.7%(24/28) with a defect in the lamina cribrosa of the internal auditory canal. The direct diagnostic sign of CSF otorrrhea could be seen in 73.9%(17/23) pre-operative MRI: two T2-weighted hyperintense signals between vestibule and middle ear cavity were connected by slightly lower or mixed intense T2-weighted signals, and obvious in the coronal-plane; 100%(23/23) hyperintense T2-weighted signals in the tympanum connected with those in the Eustachian tube.In post-operative CT, the soft tissues in the tympanum and mastoid cavity decreased or disappeared as early as one week. In post-operative MRI, the hyperintense T2-weighted signals of tympanum and mastoid decreased or disappeared in 3 days to 1 month,soft tissues tamponade with moderate intense T2-weighted signal were seen in the vestibule in 1-4 months. Conclusions: IP-Ⅰ, CC, IP-Ⅱ and CA with dilated vestibule can lead to CSF otorrhea. Combined with special medical history, T2-weighted signal of inner ear MRI can provide diagnostic basie for most children with IEM and CSF otorrhea.HRCT and MRI of inner ear can also be used to evaluate the effect of surgery.

Effectiveness of autologous hematopoietic stem cell transplantation in the treatment of high-risk neuroblastoma in children: a single-center clinical study / 中国当代儿科杂志

OBJECTIVES@#To investigate the effectiveness of high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (ASCT) in the treatment of children with high-risk neuroblastoma (NB).@*METHODS@#A retrospective analysis was performed on 29 children with high-risk NB who were admitted to Shanghai Children's Hospital and were treated with high-dose chemotherapy combined with ASCT from January 2013 to December 2021, and their clinical features and prognosis were analyzed.@*RESULTS@#Among the 29 children treated by high-dose chemotherapy combined with ASCT, there were 18 boys (62%) and 11 girls (38%), with a median age of onset of 36 (27, 59) months. According to the International Neuroblastoma Staging System, 6 children (21%) had stage III NB and 23 children (79%) had stage IV NB, and the common metastatic sites at initial diagnosis were bone in 22 children (76%), bone marrow in 21 children (72%), and intracalvarium in 4 children (14%). All 29 children achieved reconstruction of hematopoietic function after ASCT. After being followed up for a median time of 25 (17, 45) months, 21 children (72%) had continuous complete remission and 8 (28%) experienced recurrence. The 3-year overall survival rate and event-free survival rate were 68.9%±16.1% and 61.4%±14.4%, respectively. Presence of bone marrow metastasis, neuron-specific enolase ≥370 ng/mL and positive bone marrow immunophenotyping might reduce the 3-year event-free survival rate (P<0.05).@*CONCLUSIONS@#Children with high-risk NB who have bone marrow metastasis at initial diagnosis tend to have a poor prognosis. ASCT combined with high-dose chemotherapy can effectively improve the prognosis of children with NB with a favorable safety profile.

The clinical analysis of 12 patients with immunoglobulin G4 related sialoadenitis and literature review / 中华风湿病学杂志

Objective To explore the clinical characteristics of Immunoglobulin G4 (IgG4) related sialoadenitis,to analyze the difference between the IgG4 related sialoadenitis and Sj(o)gren'syndrome (SS) and to summarize the treatment method and prognosis of the disease,so as to help clinical diagnosis and appropriate treatment.Methods According to inclusion criteria and exclusione criteria,we collected 12 cases of IgG4 related sialoadenitis patients and 78 cases of SS patients from the First Affiliated Hospital of Xinjiang Medical University from 2015-2017.The clinical manifestations,laboratory test,pathological examinations,imaging examinations and the effects of treatment of IgG4 related sialoadenitis were retrospectively anal-yzed.Several aspects of the examination were compared with SS.The count data was analyzed by chi-square test or Fisher exact probality using Statistical program for social sciences (SPSS) 19.0 software.Results Characteristics of IgG4 related sialoadenitis was that one or more pairs of salivary glands and lacimal glands were enlarged with increasing serum IgG4 levels and IgG4+ plasma cell infiltration.Compared with SS,sialoadenitis enlargement (12/12 vs 18/78,x2=24.339,P＜0.01),dry eyes and mouth (9/12 vs 78/78,P＜0.01),serum IgG4 (12/12 vs 0/78,x2=81.554,P＜0.01),antinuclear antibodies (1/11 vs 78/78,x2=71.030,P＜0.01),anti-SSA antibody (0/9 vs 68/78,x2=31.001,P＜0.01),anti-SSB antibody (0/9 vs 36/78,x2=5.311,P=0.021),anti-Ro-52 antibody (0/9 vs 70/78,x2=-35.824,P＜0.01),infiltration of IgG4 positive plasma cell (12/12 vs 0/78,x2=81.554,P＜0.01),therapeutic efficacy of glucocorticoid (6/6 vs 0/34,P＜0.01) was statistically significant.Conclusion IgG4 related sialoadenitis has remarkable characteristics in clinical manifestations,serology,pathology and imaging examinations.Although IgG4 related sialoadenitis and SS have many similarities,we still need to diagnose the disease as early as possible and set up a reasonable treatment plan for patients.

The clinical analysis of 12 patients with immunoglobulin G4 related sialoadenitis and literature review / 中华风湿病学杂志

Objective@#To explore the clinical characteristics of Immunoglobulin G4 (IgG4) related sialoadenitis, to analyze the difference between the IgG4 related sialoadenitis and Sjögren′ syndrome (SS) and to summarize the treatment method and prognosis of the disease, so as to help clinical diagnosis and appro-priate treatment.@*Methods@#According to inclusion criteria and exclusione criteria, we collected 12 cases of IgG4 related sialoadenitis patients and 78 cases of SS patients from the First Affiliated Hospital of Xinjiang Medical University from 2015-2017. The clinical manifestations, laboratory test, pathological examinations, imaging examinations and the effects of treatment of IgG4 related sialoadenitis were retrospectively anal-yzed. Several aspects of the examination were compared with SS. The count data was analyzed by chi-square test or Fisher exact probality using Statistical program for social sciences (SPSS) 19.0 software.@*Results@#Character-istics of IgG4 related sialoadenitis was that one or more pairs of salivary glands and lacimal glands were enlar-ged with increasing serum IgG4 levels and IgG4+ plasma cell infiltration. Compared with SS, sialoadenitis enl-argement (12/12 vs 18/78, χ2=24.339, P<0.01), dry eyes and mouth (9/12 vs 78/78, P<0.01), serum IgG4 (12/12 vs 0/78, χ2=81.554, P<0.01), antinuclear antibodies (1/11 vs 78/78, χ2=71.030, P<0.01), anti-SSA antibody (0/9 vs 68/78,χ2=31.001, P<0.01), anti-SSB antibody (0/9 vs 36/78, χ2=5.311, P=0.021), anti-Ro-52 antibody (0/9 vs 70/78, χ2=35.824, P<0.01), infiltration of IgG4 positive plasma cell (12/12 vs 0/78, χ2=81.554, P<0.01), therapeutic efficacy of glucocorticoid (6/6 vs 0/34, P<0.01) was statistically significant.@*Conclusion@#IgG4 related sialoadenitis has remarkable characteristics in clinical manifestations, serology, pathology and imaging examinations. Although IgG4 related sialoadenitis and SS have many similarities, we still need to diagnose the disease as early as possible and set up a reasonable treatment plan for patients.

The effects of silica dust on the expression of MyD88 and TRAF6 mRNA of lung macrophages in rats / 中华劳动卫生职业病杂志

Objective@#To investigate the effects of silica dust on the expression of Myeloid differentiation factor 88 (MyD88) mRNA and tumor necrosis factor receptor-associated factor (TRAF6) mRNA of lung macrophages in rats.@*Methods@#Selecting 40 SPF-class Wistar rats with average weight (200±20) g randomly divided into control group and 30 d, 60 d, 120 d experimental groups with 10 rats in each group according to body weight. The experimental groups rats were injected with 1 ml of SiO2 (100 mg/ml) suspension through the trachea into lung only once, then they were respectively killed after 30, 60, 120 days. The control group rats were injected with 1 ml of saline into lung, and killed after 120 days. The lungs of the rats were taken for pathological observation. Lung macrophages were extracted and counted, and their activity was detected by MTT. RT-qPCR was used to assess the relative contents of MyD88 mRNA and TRAF6 mRNA.@*Results@#Silica dust inhalation led to infiltration of lung tissue cells, thickening the alveolar wall and destruction of alveolar structure. The longer the exposure to dust, the more obvious the results were. The number of macrophages in all experimental groups and activity in the 30 d, 60 d groups were significantly higher than that in the control group (P<0.05) . Among them, 30 d group had the largest number and the highest activity. Compared with the control group, the expression of MyD88 mRNA and TRAF6 mRNA of lung macrophages in rats increased in the experimental groups (P<0.05) , especially in the 60 d group.@*Conclusion@#Silica dust inhalation can increase the expression of MyD88 and TRAF6 in macrophages, suggesting that silica dust can induce silicosis fibrosis by activating TLR/NF-κB signal pathway.

[Re-operation treatment in uremic patients complicated with persistent secondary hyperparathyroidism after parathyroidectomy with autotransplantation].

Objective:To analyze the clinical profile and therapeutic effect of re-operation treatment in uremic patients complicated with persistent secondary hyperparathyroidism(SHPT)after parathyroidectomy with autotransplantation.Method:Twelve persistent SHPT patients who were treated with reoperation of paramyroidectomy(PTX)were enrolled in this study during the period from Jan 2014 to Jul 2017 in our hospital.We evaluated the location of the remaining parathyroid glands by ultrasonography,dual-phase 99 Tcm-sestamibi scintigraphy,CT and MR imaging of the neck before the operation.We resected the parathyroid gland tissue in situ,and the ectopic parathyroid glands hiding in thymus,mediastinal,tracheal esophageal groove,thyroid gland and other locations in the neck.During the surgery,nanocarbon imaging was used to help identify the parathyroid gland and parathyroid hormone assay(IOPTH)was measured at the end of the surgery.We observed the changes of clinical symptoms after the surgery and collected blood parameters including serum intact aramyroidhomone(i-PTH),calcium(Ca),phosphoms(P),calcium and phosphorus product before and after surgery.Complications and failure were also analyzed.Result:All the 12 patients underwented successful operation.The postoperative pathological results were hyperplastic parathyroid glands tissue.22 parathyroid glands were resected,among which 14 were located at the neck in situ,8 were ectopic,i.e.,located at thymus in 4 cases,superior mediastinum in 2 cases and thyroid parenchyma in 2 cases.The clinical symptoms were significantly improved including osteoarthritis,skin itching and limb weakness.The levels of serum iPTH,calcium,phosphorus and calcium and phosphorus product were significantly lower than those before operation(P<0.05).Ten patients presented hypocalcemia after surgery and the level of calcium returned to normal after supplement of calcium.Temporary injury of laryngeal nerve was found in4 cases,but there was no patient with transient bucking,dyspnea or death.No recurrence was found during 1 year follow-up.Conclusion:It was very important to locate the residual parathyroid gland accurately with a variety of imaging methods in uremic patients complicated with persistent or recurrent SHPT when they needed re-operation.Surgeons should explorate ectopic parathyroid gland according to the concept of the superior mediastinum dissection and the central compartment neck dissection.Meanwhile,the use of nanocarbon assisted parathyroid gland negative imaging and rapid IOPTH can significantly improve the success rate of surgery and reduce surgical complications.

Expression and significance of LAT1 and p-s6 breast cancer / 临床与实验病理学杂志

Purpose To investigate the expression and significance of type L amino acid transporter 1 (LAT1 ) and phosphorylated s6 ribosomal protein (p-s6) in breast cancer tissues and their correlation. Methods LAT1 protein and p-s6 protein were detected by immunohistochemical EnVision two step method in 178 cases of breast cancer and 78 cases of benign breast lesion, and the relationship between the expression and clinicopathological parameters was analyzed. Results The positive rate of LAT1 in breast cancer was 36.5％, which was significantly higher than that of breast benign lesion tissues (23.1 ％, P＜ 0.05 ), the positive rate of p-s6 in breast cancer tissues was33.2％, which was significantly higher than that of breast benign lesion tissues (12.8％, P＜0.05). There was a positive correlation between the expression of LAT1 protein and p-s6 protein in breast cancer tissues (r = 0.345, P＜ 0.05). The expression of LAT1 protein in breast cancer was correlated with tumor diameter, axillary lymph node metastasis, TNM staging and HER-2 level (P＜ 0.05), but not associated with the patient's age, histological grade, ER, and PR levels (P＞ 0.05). The expression of p-s6 protein was related to axillary lymph node metastasis, TNM staging, age and ER level (P＜ 0.05), but not associated with tumor diameter, histological grade, PR and HER-2 levels (P＞ 0.05 ). Multivariate analysis showed that the expres sion of LAT1 protein was related to tumor diameter and expression level of HER-2. The expression of p-s6 protein was related to axillary lymph node metastasis. Conclusion The expression of LAT1 protein and p-s6 protein in breast cancer is up-regulated, and the expression of these two proteins is positively related, which implying that LAT1 and p-s6 might play a synergistic role in the development and progression of breast cancer.

Multicenter clinical trial of acute lymphoblastic leukemia in elder children and adolescents / 中华血液学杂志

Objective: To analyze the clinical characteristics and long-term outcomes with multicenter study for acute lymphoblastic leukemia (ALL) in children over 10 years old and adolescents. Method: Newly diagnosed ALL patients aged from 10 to 18 years old in three hospitals were included in the study from May 1(st) 2005 to April 30(th) 2015. They were received ALL-2005/2009 protocol following up to December 31(st) 2016. The clinical characteristics, outcomes and the prognostic analysis were evaluated between the two protocols. Results: Totally, 237 patients were involved in the study, 76 cases for ALL-2005 and 161 cases for ALL-2009 protocol. Complete remission (CR) after induction therapy was 94.5%. 64 (28.6%) patients relapsed with a median time of 14.5 months and 70 (29.5%) patients passed away during the following time. In long-term follow-up, the 5-year event-free survival (EFS) and 5-year overall survival (OS) of ALL patients were (63.1±3.3)% and (68.4±3.2)%. The 7-year EFS and OS were (61.0±3.5)% and (67.6±3.3)%.The 5-year EFS of intermediate risk group in ALL-2005 and ALL-2009 protocol were (73.6±6.1)% and (71.7±4.3)% with no difference (χ(2)=0.064, P=0.801). The 5-year EFS of high risk group in two protocols were (27.6±9.6)% and (33.9±9.3)%, showing no significant difference (χ(2)=0.296, P=0.586). Five years relapsed rate of two protocols were (33.8±5.7)% and (32.6±4.1)% with no difference (χ(2)=0.055, P=0.815). The mortalities were 36.8% and 29.8% separately (χ(2)=2.869, P=0.090). Univariate analysis indicated that age, male, risk, BCR/ABL translocation/t(9;22) and resistant to induction were risk prognostic factors in long-term survival (χ(2)=4.764, 4.796, 46.410, 9.560, 25.450; P=0.029, 0.029, <0.001, 0.049, <0.001). Cox multivariate analysis showed male, risk and resistant to induction were independent risk prognostic factors (RR=1.790, 2.727, 2.719; P=0.021, 0.000, 0.012). Conclusion: Protocol ALL-2009 enhanced the chemotherapy intensity in intermediate risk group with no benefit of survival. BCR-ABL fusion or t(9;22) translocation was still the risk factor of prognosis. TKI inhibitor used in these patients could improve survival. EFS rate was increased a little and death rate was decreased in ALL-2009 protocol with no significant lower relapsed rate comparing with ALL-2005 protocol.

Study of intracellular location of adenovirus protein IX with correlative light and electron microscopy based on miniSOG / 中华实验和临床病毒学杂志

Objective@#To establish a method of correlative light and electron microscopy (CLEM) to study the intracellular location of adenovirus protein IX.@*Methods@#MiniSOG (mini singlet oxygen generator) is a recently-invented genetically-encoded tag for CLEM. MiniSOG-fused adenovirus IX gene (IXSOG) was cloned by PCR, and inserted into pcDNA3 plasmid to form pTPL-IXSOG, which was used to transfect 293 cells. IXSOG expressing cells could be distinguished under fluorescence microscope due to the emission of green fluorescence of miniSOG. The transfected cells were fixed in 2.5% glutaraldehyde in situ, stained with diaminobenzidine(DAB) through the photooxidation activity of miniSOG, and used to prepare ultrathin sections. Intracellular location of IXSOG was studied by observing the sections under transmission electron microscope.@*Results@#Eukaryotic expression plasmid carrying IXSOG fusion gene was constructed. IXSOG expressing cells were selected for DAB photooxidation and preparation of ultrathin sections. IXSOG fusion mainly formed punctate aggregations or inclusions in the nucleus.@*Conclusions@#The correlative light and electron microscopy method based on miniSOG was successfully established, and it could be used to study the intracellular localization of viral proteins.

Relationship between the expression of TIP30 and clinico-pathological characteristics in extrahepatic cholangiocarcinoma / 中国现代普通外科进展

Objective:To investigate the expression of TIP30 and its relationship with clinico-pathological characteristics in patients with extrahepatic cholangiocarcinoma (ECC).Methods:The expression of TIP30 in 78 cases of ECC tissues and 78 cases of para-cancerous tissues were detected by immunohistochemistry.Results:The positive expression rate of TIP30 was 43.59％ and 75.64％ in ECC tissues and para-cancerous tissues,respectively.Differences were statistically significant (P＜ 0.05).The expression levels of TIP30 were not correlated with age,gender,degree of differentiation and tumor size(P＞0.05),but correlated with lymph node metastasis,distant metastasis and TNM staging(P＜ 0.05).The median overall survival of 78 ECC cases was 14.8 months,and it of TIP30 positive expression cases was 20.3 months,statistically higher than 11.5 months in TIP30 negative expression cases(P＜ 0.01).Conclusion:The downregulation of TIP30 is closely correlated with the development,metastasis and prognosis of ECC.TIP30 may be used as a molecular marker to identify and predict the progression,metastasis and prognosis of ECC.

Design and application of Shenmen point electronic stimulator for attenuating insomnia and anxiety / 医疗卫生装备

Objective To design and manufacture a Shenmen point electronic stimulator and determine its therapeutic effects for insomnia and anxiety.Methods The stimulator was composed of a single point electrode unit and an electronic stimulation generator.The single point electrode unit consisted of a circular transdermal patch and two circular electrodes which was used for precision stimulation on Shenmen point.The electronic stimulation generator released low-frequency square-wave pulse current based on specific parameters to treat the examinees with insomnia and anxiety.The curative effect of the stimulator was tested by Hamilton rating scale for anxiety and evaluation on improved sleeping.Results The stimulator executed precision stimulation based on specific requirements on the point.30-min treatment with the stimulator before sleeping in 10 d contributed to significantly decreasing Hamilton rating scores for anxiety and improving sleeping quality.Conclusion The stimulator markedly attenuates anxiety and insomnia,and can be a convenient,effective and safe choice for adjunctive therapy of insomnia and anxiety.

Design and application of Shenmen point electronic stimulator for attenuating insomnia and anxiety / 医疗卫生装备

Objective To design and manufacture a Shenmen point electronic stimulator and determine its therapeutic effects for insomnia and anxiety.Methods The stimulator was composed of a single point electrode unit and an electronic stimulation generator.The single point electrode unit consisted of a circular transdermal patch and two circular electrodes which was used for precision stimulation on Shenmen point.The electronic stimulation generator released low-frequency square-wave pulse current based on specific parameters to treat the examinees with insomnia and anxiety.The curative effect of the stimulator was tested by Hamilton rating scale for anxiety and evaluation on improved sleeping.Results The stimulator executed precision stimulation based on specific requirements on the point.30-min treatment with the stimulator before sleeping in 10 d contributed to significantly decreasing Hamilton rating scores for anxiety and improving sleeping quality.Conclusion The stimulator markedly attenuates anxiety and insomnia,and can be a convenient,effective and safe choice for adjunctive therapy of insomnia and anxiety.

Midterm clinical outcomes and radiological results of surgical treatment for Hirayama disease / 北京大学学报(医学版)

Objective:To assess the midterm clinical and radiological outcomes of internal fixation and fusion for the treatment of Hirayama disease and to evaluate the clinical significance and value of this procedure.Methods:In the study,36 patients were treated with anterior cervical internal fixation and fusion.The clinical outcomes including muscle strength and atrophy were recorded.The radiological outcomes including range of motion of cervical spine and the cross-sectional area of spinal cord at each level on MRI scan were measured before and at 3 month,1 year and 2 years follow-up time points after surgery.Results:(1) Clinical outcomes:all the patients showed no further progression of symptoms except one patient with mild progression of muscular weakness and atrophy.As the time passed by,the ratio of the patients with muscle strength and atrophy improvement increased.There were 26.5 ％ of patients in 3 months,36.0％ in 1 year and 85.7％ in 2 years who experienced muscle strength improvement.8.8％ of patients in 3 months,24.0％ in 1 year and 35.8％ in 2 years felt muscle atrophy improvement.And 12 of the 14 patients showed improved muscle strength and atrophy at the end of 2 years period follow-up.(2) Radiological outcomes:the range of motion (ROM) of C2-C7 was significantly decreased after the operation.The ROM of preoperation was 62.25° ±2.10° and that of 2 years postoperation was 13.67° ± 7.51°(P ＜ 0.01).The spinal cord was of no compression on flexion MRI.The cross-section area of spinal cord on MRI was significantly increased only at C6 level (P ＜0.05) at the end of three months follow-up.The level of increased cross-section area rose to C4-C5-C6 levels (P ＜0.01) in 1 year and to C4-C5-C6-C7 levels at the end of 2 years follow-up P ＜ 0.05).The cross-section area increased 15.60％ at C4,19.08％ at C5,21.60％ at C6 and 23.91％ at C7 with significant difference (P ＜0.05) 2 years after the operation.Conclusion:Anterior cervical internal fixation and fusion is an effective surgical treatment for Hirayama disease and may provide preferable midterm clinical and radiological outcomes.This procedure has clinical significance and value in terms of control of the progression and outcome of this disease.

Simvastatin protect retinal ganglion cells against optic nerve crush in mice / 眼科新进展

Objectivc To investigate the protective effect of simvastatin on retinal ganglion cells (RGC) after optic nerve crush (ONC).Methods Together 50 Kunming mice were randomly divided into normal group,sham group,ONC group and simvastatin protection group.The mice in the normal group were untreated,the sham group was treated with the exposure of the optic nerve without injury,the ONC group mice underwent ONC operation on the left eyes,followed by intravitreal administration of equilibrium solvent [50 mg · mL-1 ethanol plus 1 mol · L-1 NaOH,which were activated by 1 mol · L-1 HC1 (pH 7.2)],and the simvastatin protection group was intravitreally injected different concentrations of simvastatin (0.5 g · L-1,1.0 g · L-1,1.5 g · L-1) after ONC operation.Brn3a immunofluorescence staining,HE staining and toluidine blue staining were used to detect the apoptosis of RGC and pathological changes of optic nerve.Results On day 7 after operation,in the ONC group,the apoptosis of RGC was observed obviously,with the survival rate dropping to (35.1 ± 3.9) ％,and the thickness from the retinal ganglion cell layer to outer nuclear layer was decreased from (123.13 ± 1.04) μm to (97.48 ± 2.33) μm,which was significantly thinner than that in the control group (P ＜ 0.01);moreover,the fibrous bundle of optic nerve disappeared,and the neuroglial cells were clustered into groups,as well as the axons showed swelling and serious degeneration,but after intravitreal injection of 1.0 g · L-1 simvastatin,the survival rate of retinal ganglion cells increased to (76.3 ± 3.7) ％ (P ＜ 0.05),and the aforementioned thickness was increased to (111.39 ± 4.06) μm,which was statistically significant when compared with the ONC group (P ＜ 0.01).The degeneration of optic nerve was improved,and the structure of neuroglial cell axons and the nerve fibers became normal.Conclusion Simvastatin can reduce the optic nerve degeneration and improve the survival rote of retinal ganglion cells.

Ertapenem versus piperacillin/tazobactam for diabetic foot infections in China: a Phase 3, multicentre, randomized, double-blind, active-controlled, non-inferiority trial.

OBJECTIVES: Few randomized controlled studies have compared antibiotic regimens against diabetic foot infections (DFIs) in Chinese patients. We evaluated the efficacy and safety of ertapenem versus piperacillin/tazobactam for the treatment of DFIs in Chinese patients. METHODS: Patients with moderate to severe DFIs requiring parenteral antibiotics were randomized in a 1 : 1 ratio to receive ertapenem (1.0 g once daily) or piperacillin/tazobactam (4.5 g every 8 h) by 30 min intravenous (iv) infusions for ≥5 days. The primary outcome was favourable clinical response at discontinuation of iv therapy (DCIV). An evaluable-patient population was identified for primary analysis of non-inferiority at -15%. Safety was assessed. ClinicalTrials.gov: NCT01370616. RESULTS: Of 565 patients randomized, 443 patients (ertapenem = 219 and piperacillin/tazobactam = 224) were clinically evaluable for primary analysis. In the clinically evaluable population, the proportions of patients with favourable clinical response at DCIV were 93.6% (205/219) and 97.3% (218/224) in the ertapenem and piperacillin/tazobactam groups, respectively (difference: -3.8%, 95% CI: -8.3%, 0.0%). Ertapenem had a significantly lower favourable clinical response rate (91.5% versus 97.2%, 95% CI for difference: -12.1%, -0.3%) at DCIV in severe DFI patients. In the modified ITT population, 88.8% (237/267) and 90.6% (241/266) of patients in the ertapenem and piperacillin/tazobactam groups, respectively, had favourable clinical responses at DCIV (difference: -1.9%, 95% CI: -7.3%, 3.3%). Microbiological eradications of causative pathogens and adverse events were similar between treatment groups. CONCLUSIONS: Treatment with ertapenem was non-inferior to piperacillin/tazobactam in Chinese patients with DFIs. Ertapenem treatment resulted in a markedly lower rate of clinical resolution in severe DFIs.

Platelets Decrease the Sensitivity of Leukemia Cell L1210 to Multiple Drugs via Activiting The AKT and ERK Signalling Pathway / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of platelets on signal transducers and the sensitivity of leukemia cells to chemotherapeuticl drugs in leukemia cells L1210.</p><p><b>METHODS</b>Murine platelets were prepared and cocultured with leukemia L1210 cells, and the aggregation between them was observed by flow cytometry. The levels of several transducer proteins in leukemia cells were analyzed with Western blot. In some experiments, methotrexate, vincristine or doxorubicin was added to the coculture system and the cell proliferation was measured by using CCK8 colorigenic methods to detect the sensitivity of leukemia cells to the therapeuticals drugs.</p><p><b>RESULTS</b>Platelets, either freshly prepared or fixed with 1% paraformaldehyde, aggregated with leukemia cells. Both fresh and fixed platelets increased the level of phosphorylation of AKT and ERK in leukemia cells as measured with Western blot. Also, platelets significantly decreased the sensitivity of 3 therapeutics to L1210 cells.</p><p><b>CONCLUSION</b>Platelets may bind with L1210 cells and decrease the sensitivity of the leukemia cells to chemotherapeutics, possibly by activating the AKT and ERK signaling pathways.</p>

Expression Changes of Matrix Reconstitution-related Genes in Bone Marrow during 5-Fluorouracil-Induced Hemopoietic Injury and Their Significance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the expression change of the genes related with matrix reconstitution during the injury and reconstitution of murine bone marrow following treatment with 5-fluorouracil (5-FU).</p><p><b>METHODS</b>C57BL/6 mice received intraperitoneal injection of 5-FU (200 mg/kg), and peripheral blood cell counts were monitored at 3, 6, 9, 15, 21, 27 days after treatment. Bone marrow cells were harvested at these times for total RNA extraction using TRIzol. Reverse transcriptions in combination with real-time PCR were performed for detecting expression of genes related with matrix reconstitution, including ECM-1, MMP-2, MMP-3, MMP-13 and TIMP-1.</p><p><b>RESULTS</b>After injection of 5-FU, the numbers of three line cells in peripheral blood (i.e. RBC, WBC and platelets) decreased and then recovered with differential dynamics. Similarly, RT-qPCR revealed that all the 5 detected gene expressions were significantly up-regulated during the injury. The mRNA expression of MMP-2 reached to peak at day 3 while the other genes reached to peak at day 6. MMP-3 has a low expression when compared with others, but its expression increased significantly after injury.</p><p><b>CONCLUSION</b>In 5-FU induced hematopoietic injury and reconstitution model, matrix reconstitution-related genes may play an important role in hematopoietic reconstitution, but different genes play different roles at various time, and cooperate with each other for hematopoietic reconstitution.</p>