Clinical Evaluation of a Vancomycin Dosage Strategy Based on a Serum Trough Concentration Model in Elderly Patients with Severe Pneumonia / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to evaluate the clinical benefits of a vancomycin dosage strategy based on a serum trough concentration model in elderly patients.@*METHODS@#This prospective single-center, open-label, randomized controlled trial categorized 66 elderly patients with severe pneumonia into study and control groups. The control group received vancomycin using a regimen decided by the attending physician. Meanwhile, the study group received individualized vancomycin therapy with a dosing strategy based on a serum trough concentration model. The primary endpoint was the proportion of patients with serum trough concentrations reaching the target values. The secondary endpoints were clinical response, vancomycin treatment duration, and vancomycin-associated acute kidney injury (VA-AKI) occurrence.@*RESULTS@#All patients were at least 60 years old (median age = 81 years). The proportion of patients with target trough concentration achievement (≥ 15 mg/L) with the initial vancomycin regimen was significantly higher in the study group compared to the control group (75.8% vs. 42.4%, P = 0.006). Forty-five patients (68.2%) achieved clinical success, the median duration of vancomycin therapy was 10.0 days, and VA-AKI occurred in eight patients (12.1%). However, there were no significant differences in these parameters between the two groups. The model for predicting vancomycin trough concentrations was upgraded to: serum trough concentration (mg/L) = 17.194 - 0.104 × creatinine clearance rate (mL/min) + 0.313 × vancomycin daily dose [(mg/(kg∙d)].@*CONCLUSION@#A vancomycin dosage strategy based on a serum trough concentration model can improve the proportion of patients achieving target trough concentrations in elderly patients with severe pneumonia.

Correlation between theta-gamma neural oscillations in hippocampal CA3 area and the spatial identifying and cognitive ability in rats / 生理学报

The present study was aimed to explore the correlation between θ-γ neural oscillations phase-amplitude coupling (PAC) in hippocampal CA3 area and the changes of spatial identifying and cognitive ability before and after shock avoidance training in rats. According to the results of Y-type maze shock avoidance training, the rats were divided into two groups: the fast avoidance response group and the general avoidance response group. The local field potential (LFP) of hippocampal CA3 area was recorded by wireless telemetry before and after shock avoidance training. The variation of θ oscillation (3-7 Hz) and low-γ neural oscillation (30-60 Hz) PAC in hippocampal CA3 area was analyzed by MATLAB wavelet packet extraction technique. The results showed that, compared with the general avoidance response group, the fast avoidance response group exhibited higher θ-γ neural oscillation PAC in hippocampal CA3 area before training. θ-γ oscillation PAC in hippocampal CA3 area was increased in both groups after training. It was also noticed that θ-γ neural oscillation PAC of some frequency bands in the general avoidance response group were significantly higher than those in the fast avoidance response group. The results suggest that certain intensity of training can change the spatial identifying and cognitive ability of rats, and the mechanism may involve the increase of the synchrony of θ-γ neural oscillation, i.e., the enhancement of θ-γ phase-amplitude alternating frequency coupling in hippocampal neurons.

Celastrol inhibits PAK1 kinase and inhibits the proliferation of pancreatic cancer cells / 药学学报

The p21-activated kinase 1 (PAK1) is a member of the P21-activated protein kinase family that plays an important role in the proliferation and on cogenesis of pancreatic cancer. PAK1 is an important target for the treatment of pancreatic cancer. At present, akinase inhibitor targeting PAK1 is still in the preclinical research stage. Therefore, screening for new PAK1 kinase inhibitors is of great significance. In this study the natural compound celastrol was found to have a significant inhibitory effect on PAK1, with an IC50 value of 3.614 μmol·L-1. Molecular docking results showed that celastrol had good binding to PAK1. An MTT assay indicated that celastrol inhibited the proliferation of pancreatic cancer cells BxPC-3 and PANC-1. Mechanistic studies revealed that the inhibition of pancreatic cancer cells by celastrol was reversed by PAK1 siRNA. Celastrol inhibited PAK1 and the subsequent activation of downstream signaling pathways, thereby activating apoptosis signaling pathways and triggering apoptosis in pancreatic cancer cells. These findings suggested that celastrol induced apoptosis in pancreatic cancer cells by suppressing the PAK1 kinase signaling pathway and has potential value for the treatment of pancreatic cancer.

Study on technological conditions of complex extraction of isoliquiritin / 中草药

Objective: To investigate the effect of extraction and reverse extraction conditions on the transfer of isoliquiritin. Methods: The extraction rate of isoliquiritin was used as the index to determine the best composition and concentration of complexing extractant. Taking the reverse extraction rate of isoliquiritin as the index, the species and concentration of the reverse extraction agent were investigated, and finally the technological conditions for the extraction and reverse extraction of isoliquiritin from glycyrrhizin ultrafiltration were obtained. Results: The best complexation extraction condition was: the ratio of TRPO to sulfonated kerosene was 7:93, and the extraction rate of isoliquiritin reached 97.60%. The best reverse extraction agent was 0.26% NaOH aqueous solution, and the reverse extraction rate of isoliquiritin reached 95.40%. Conclusion: Under the optimal conditions of extraction and reverse extraction obtained in this experiment, isoliquiritin can be transferred from glycyrrhizin ultrafiltration to complexing extractant and then to alkaline reverse extraction agent, and finally isoliquiritin can be obtained by extraction and reverse extraction.

IL-17D regulates recruitment of lung NK cells and promotion of Astragalus membranaceus / 中国免疫学杂志

Objective:To investigate the role of IL-17D to regulate the recruitment of lung NK cells and the effects of Astragalus membranaceus on IL-17D.Methods:The lung metastasis of tumor model was established by injecting B16 melanoma cells through caudal vein.After being treated with IL-17D or Astragalus membranaceus respectively,the expression of IL-17D and NK cells in lung was detected by flow cytometry and RT-PCR.Results:The production of IL-17D and the content of NK cells in the lung tumor me-tastasis model were dramatically decreased.After treatment with IL-17D,the content of NK cells in lung was significantly increased and the lung tumor foci were decreased.Along with up-regulated recruitments of NK cells,CXCL9 and IL-15,which support NK cell recruitments and maintain survival,were significantly increased.Astragalus inhibited lung tumor developments in lung by increasing the IL-17D expression and up-regulated the lung NK cell content.Conclusion: IL-17D can regulate the lung recruitment of NK cells.Astragalus mongholicus can enhance the capacity of NK cell recruitment and promote anti-tumor immune effects by up-regulating the expression of IL-17D.

Clinical Analysis of 7 Children with Mature B-cell Acute Lymphoblastic Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of CCCG-BNHL-2015 protocol in treatment of children with mature B-cell acute lymphoblastic leukemia (mature B-ALL).</p><p><b>METHODS</b>Seven pediatric patients with newly diagnosed mature B-ALL were treated by CCCG-BNHL-2015 protocol (risk group R4) in Children's Hospital of Nanjing Medical University from November 2014 to January 2017.</p><p><b>RESULTS</b>The median age of patients at initial diagnosis was 7.2 years (range 4.1 to 11.75 years) with a male predominance (5:2), the clinical characters were as follows: 4 cases combined with thoracic and/or abdominal lumps, only lymphonode was involved in 1 case, bone destruction was complicated in 2 cases and 1 case was complicated with central nervous system leukemia. In 2 children, tumor lysis syndrome appeared at early phase. The lactate dehydrogenase level at diagnosis of all patients extremely increased. All patients achieved complete remission after 2 to 4 courses of therapy. Two among them underwent autologous hematopoietic stem cell transplantation. One with primary central nervous system leukemia relapsed before the last course, then the treatment was abandoned. The rest of 6 patients survived with a median follow-up period of 14 months (ranged from 7 to 28 months), and suffered from different degrees of myelosuppression and infection. No one died from serious complications.</p><p><b>CONCLUSION</b>The CCCG-BNHL-2015 protocol (risk group R4) shows better curative effect, higher safety and remission rate in childhood mature B-cell lymphoblastic leukemia.</p>

Changes of Peripheral Blood Marrow-Derived Suppressor Cell Level after Chemotherapy Induction Remission by VDLP Regimen and Their Relationship with Immune System in B-ALL Children / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the changes of peripheral blood marrow-derived suppressor cell level after chemotherapy induction remission by regimen consisting of vincristine, daunorubicin, L-asparaginase and prednisone (VDLP) and to analyze their relationship with immume system in B-ALL children.</p><p><b>METHODS</b>Thirty B-ALL children after induction remission by VDLP regimen from August 2015 to August 2016 were selected as B-ALL group and 30 normal healthy children were selected as control group. The peripheral blood in 2 groups was collected and detected by flow cytometry, then the ratios of CD30cells and CD33HLA-DRmarrow-derived suppressor cells, CD14CD33HLA-DRmarrow-derived suppressor cells and CD15CD33HLA-DRmarrow-derived suppressor cells were calculated, and their changes after induction remission by VDLP regimen and the relationship with immune system were analyzed.</p><p><b>RESULTS</b>After treatment the ratio of CD33cells in peripheral blood of B-ALL group and control group was not significantly different (P> 0.05), moreover, the ratio of CD33cells in B-ALL group was significantly higher than that before treatment (P<0.05), while the ratios of CD33HLA-DRmarrow-derived suppressor cells, CD14CD33HLA-DRmarrow-derived suppressor cells and CD15CD33HLA-DRmarrow-derived suppressor cells in B-ALL group were significantly lower than those in control group (all P<0.05), but the ratios of these cells in B-ALL group were higher than those before treatment, and yet there was no statistical significance (P>0.05).</p><p><b>CONCLUSION</b>The ratios of marrow-derived suppressor cells in peripheral blood of B-ALL children in complete remission after treatment with VDLP regimen are higher than those before treatment, but are significantly lower than normal value, which may be related with non-complese recovery of immune system in B-ALL children after treatment.</p>

Comparison of the histological morphology between normal skin and scar tissue / 华中科技大学学报（医学）（英德文版）

Skin wound healing is a complex event, and interrupted wound healing process could lead to scar formation. The aim of this study was to examine the morphological changes of scar tissue. Pathological staining (HE staining, Masson's trichrome staining, methenamine silver staining) was used to evaluate the morphological changes of regenerating epidermis in normal skin and scar tissue, and immunofluorescence staining to detect the expression of collagen IV, a component of basement membrane (BM), and the expression of integrinβ4, a receptor for BM laminins. Additionally, the expression of CK14, CK5, and CK10 was measured to evaluate the proliferation and differentiation of keratinocytes in normal skin and scar tissue. The results showed that the structure of the skin was histologically changed in scar tissue. Collagen IV, expressed under the epidermis of normal skin, was reduced distinctly in scar tissue. Integrinβ4, expressed in the basal layer of normal skin, was found absent in the basal layer of scar tissue. Additionally, it was found that keratinocytes in scarring epidermis were more proliferative than in normal skin. These results indicate that during the skin wound healing, altered formation of BM may affect the proliferation of keratinocytes, reepithelial and tissue remodeling, and then result in scar formation. Thus, remodeling BM structure during wound repair may be beneficial for improving healing in cutaneous wounds during clinical practice.

Comparison of the histological morphology between normal skin and scar tissue / 华中科技大学学报（医学）（英德文版）

Skin wound healing is a complex event, and interrupted wound healing process could lead to scar formation. The aim of this study was to examine the morphological changes of scar tissue. Pathological staining (HE staining, Masson's trichrome staining, methenamine silver staining) was used to evaluate the morphological changes of regenerating epidermis in normal skin and scar tissue, and immunofluorescence staining to detect the expression of collagen IV, a component of basement membrane (BM), and the expression of integrinβ4, a receptor for BM laminins. Additionally, the expression of CK14, CK5, and CK10 was measured to evaluate the proliferation and differentiation of keratinocytes in normal skin and scar tissue. The results showed that the structure of the skin was histologically changed in scar tissue. Collagen IV, expressed under the epidermis of normal skin, was reduced distinctly in scar tissue. Integrinβ4, expressed in the basal layer of normal skin, was found absent in the basal layer of scar tissue. Additionally, it was found that keratinocytes in scarring epidermis were more proliferative than in normal skin. These results indicate that during the skin wound healing, altered formation of BM may affect the proliferation of keratinocytes, reepithelial and tissue remodeling, and then result in scar formation. Thus, remodeling BM structure during wound repair may be beneficial for improving healing in cutaneous wounds during clinical practice.

Isoprenaline Induces Periostin Expression in Gastric Cancer

PURPOSE: Periostin mediates critical steps in gastric cancer and is involved in various signaling pathways. However, the roles of periostin in promoting gastric cancer metastasis are not clear. The aim of this study was to investigate the relevance between periostin expression and gastric cancer progression and the role of stress-related hormones in the regulation of cancer development and progression. MATERIALS AND METHODS: Normal, cancerous and metastatic gastric tissues were collected from patients diagnosed with advanced gastric cancer. The in vivo expression of periostin was evaluated by in situ hybridization and immunofluorescent staining. Meanwhile, human gastric adenocarcinoma cell lines MKN-45 and BGC-803 were used to detect the in vitro expression of periostin by using quantitative real-time polymerase chain reaction (PCR) and western blotting. RESULTS: Periostin is expressed in the stroma of the primary gastric tumors and metastases, but not in normal gastric tissue. In addition, we observed that periostin is located mainly in pericryptal fibroblasts, but not in the tumor cells, and strongly correlated to the expression of α-smooth muscle actin (SMA). Furthermore, the distribution patterns of periostin were broader as the clinical staging of tumors progressed. We also identified a role of stress-related signaling in promoting cancer development and progression, and found that isoprenaline upregulated expression levels of periostin in gastric cancer cells. CONCLUSION: These findings suggest that the distribution pattern of periostin was broader as the clinical staging of the tumor progressed and found that isoprenaline upregulated expression levels of periostin in gastric cancer cells.

Polymorphisms in NF-KB pathway genes and their association with risk of lung cancer in the Chinese population

Objective:To investigate the association of NFKB1 -94 ins/del ATTG, NFKBIA -826C>T and NFKBIA -881A>G polymorphisms with risk of lung cancer in a Chinese population

Methods:Genotyping of the polymorphisms were performed on 1,436 subjects [718 cases and 718 controls] by using PCR-RFLP technique, followed by DNA sequencing

Results:We found a significant risk reduction associated with heterozygous ins/del [OR=0.705, 95% CI=0.566-0.878, P=0.002] and variant del/del [OR=0.342, 95% CI=0.221-0.528, P<0.001] genotypes of the NFKB1 polymorphism. In contrast, the heterozygous and variantgenotypes of theNFKBIA polymorphisms showed association with increased lung cancer risk [NFKBIA -826 CT,OR=1.256, 95%CI=1.004-1.572, P=0.046; TT,OR=1.773, 95% CI=1.131-2.778, P=0.013; NFKBIA -881 AG,OR=1.277, 95% CI=1.023-1.599, P=0.031; GG,OR=1.801, 95% CI=1.169-2.775, P=0.008]. Several genotypic combinations of the three polymorphisms also showed significant association with lung cancer risk. The risk association of NFKB1 polymorphism remained significant when analyses were done according to gender and smoking status [P<0.05]. The significance of NFKBIA risk association was not observed when gender-specific analyses were made [P>0.05], while only NFKBIA -881 GG genotype showed significant risk association among smokers when analyzed according to smoking status [P=0.032]

Conclusions: Polymorphisms in NFKB1 and NFKBIAgenes were associated with risk of lung cancer

The Status of iron deficiency anemia and its effect on growth and development among infants / 预防医学

Objective To know the prevalence rate of iron deficiency anemia and its effect on growth and development among infants under 6 months. Methods A total of 341 infants who were born from July 2011 to June 2012 were enrolled. The information of blood routine examination,growth index,feeding patterns was collected at age of 42 days and 6 months,respectively. Developmental screening test was conducted at age of 6 months. Results The prevalence rate of anemia at 42 days was 37. 54%,and there was no significant difference between males(40. 54%)and females(33. 97%) (P>0. 05). The prevalence rate of iron deficiency anemia at 6 months was 19. 35%,in which 48. 48% were new cases. At age of 42 days,there was no significant difference between different feeding patterns in anemia prevalence( breast feeding:30. 82%,mixed feeding:41. 40%,artificial feeding:47. 37%,P>0. 05). While at age of 6 months,the anemia prevalence of breast feeding group was higher( 38. 20%)than that of the other two groups( mixed feeding:16. 38%;artificial feeding:9. 56%;P<0. 05 ). The rate of developmental quotient below 70 was 11. 76% in the anemia cases whose hemoglobin was continuously low from 42 days to 6 months,which was higher than that of new onset anemia cases (3. 13%)and normal hemoglobin controls(1. 82%)(P<0. 05). Conclusion Continuously low hemoglobin at early age of 42 days to 6 months is potentially harmful to neuropsychological development of infants. Early screening of hemoglobin is urgently needed for intervention of iron deficiency anemia among infants.

Influence of methylenetetrahydrofolate reductase gene polymorphisms on antidepressant response / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the influence of polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene on response to antidepressant treatment.</p><p><b>METHODS</b>Two hundred and eight one Chinese Han patients have received single antidepressant drugs for at least 6 weeks, among whom 275 were followed up for 8 weeks. Hamilton depression scale 17 (HAMD-17) was used to evaluate the severity of depressive symptoms and therapeutic effects. Single nucleotide polymorphisms (SNPs) of the MTHFR gene were determined using gene chips. Associations of single loci and haplotypes with response to treatment were analyzed using an Unphased 3.0.13 software.</p><p><b>RESULTS</b>No significant differences in gender, age, year of education, family history, episode times, and antidepressant agents were found between responders and non-responders (all P U+003E 0.05), while the baseline scores of HAMD-17 was significantly different(t=2.891, P=0.004). There was also no significant difference between age, years of education, family history, baseline scores of HAMD-17 and antidepressant agents between remitters and non-remitters (both P U+003E 0.05), while proportion of male patients was significantly higher in non-remission group than remission group (t=2.381, P=0.018), and episode times in non-remission group was significantly higher (t=-1.983, P=0.049). Single locus association analysis has found no significant association between SNPs rs1801131 and rs1801133 in the MTHFR gene with antidepressant response (P U+003E 0.05). On the other hand, haplotype A-C of MTHFR gene (rs1801131 and rs1801133) was significantly associated with antidepressant response in total group (U+03C7 2=11.39, P=0.0007), male subgroup (U+03C7 2=8.767, P=0.003) and serotonin noradrenaline reuptake inhibitors (SNRIs) subgroup (U+03C7 2=10.51, P=0.001).</p><p><b>CONCLUSION</b>Particular haplotype of MTHFR gene may be related with antidepressant effect, in which the haplotype (rs1801131, rs1801133) A-C type may be associated with better antidepressant efficacy, particularly in males and patients receiving SNRIs drugs.</p>

Recent researches of synthetic mercury sulfide in traditional medicine system / 中国中药杂志

<p><b>OBJECTIVE</b>Herein, the synthesis, component, microstructure and pharmacological and toxicology researches of the Synthetic Mercury Sulfide (S-HgS) a kind of common drug in Chinese, Mongolia, Tibetan medicine, and Indian medicine system were summarized. The similar cognition about mercury toxicity & pharmacological action from some Asian regions was analyzed, and it can supply some useful direction for the traditional Asian medicine system.</p><p><b>METHOD</b>Recent literatures both domestic and abroad were summarized and analyzed.</p><p><b>RESULT</b>S-HgS is the basis of Vermilion, Mongolia-Vermilion, Zuotai, and Ras-sindoor. Athough the processes of synthesis are very different, but the microstructure and pharmacological & toxicology of S-HgS is similar.</p><p><b>CONCLUSION</b>S-HgS has a far-ranging application,and unique curative effect. New technology such as nanotechnology can be used for improving the advancement of traditional Asian medicine.</p>

Dedifferentiation of epidermal cells into transit amplifying cells induced by bFGF / 南方医科大学学报

<p><b>OBJECTIVE</b>TTo explore the method for inducing the dedifferentiation of epidermal cells into their progenitor stem cells in vitro without external gene intervention.</p><p><b>METHODS</b>HEK cells obtained from Casacade were induced to reverse their differentiated process and produce immature stem-like cells, namely the dedifferentiation derived epidermal stem cells (dESCs), by induction with basic fibroblasts growth factors (bFGF) in vitro. Immunochemical staining, flow FACS analysis, RT-PCR and immunofluorescent staining were used to detect the phenotypic and functional changes of the differentiated epidermal cells, using human epidermal stem cells (ESCs) as the positive control.</p><p><b>RESULTS</b>Immunohistochemical staining revealed that the expressions of β₁-integrin, CK19 and CK14 were up-regulated, while CK10 expression was down-regulated significantly after bFGF treatment. Two-color flow cytometric analysis of α₆-integrin and CD71 showed that the percentages of α₆(+)CD71(-), α₆(+)CD71(+) and CD71(+) expressing populations reached 13.24%, 58.26% and 23.12% of the total isolated cells, as compared with those of the control (0.12%, 3.06%, 51.50%) and positive control cells (37.49%, 45.13%, 5.86%). RT-PCR analysis indicated that the relative gene expressions of β₁-integrin, CK19 and CK14 increased in bFGF treatment group, whereas the expression of CK10 was significantly suppressed. Although there was no significant difference in the expression levels of β₁ integrin, CK19 and CK10 between the bFGF-treated and the positive controls, the expression of CK14 in bFGF-treated cells showed a 1.4-fold increase as compared with that in ESCs (P < 0.05). Immunofluorescent staining showed that a regional difference in the subcellular localization of telomerase between dESCs and ESCs.</p><p><b>CONCLUSION</b>bFGF can induce the epidermal cells to convert into epidermal precursor cells. Although they are more likely to be transient amplifying cells, the method for reprogramming somatic epidermal cells into their progenitors by bFGF induction other than genetic manipulation offers a new approach to generate residual healthy stem cells for wound repair and regeneration.</p>

Construction of fusion expression vector EGFP-PDX-1 and its transfection into rat fetal hepatic stem cells by electroporation / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct the fusion expression vector of pancreatic-duodenal homeobox gene 1 (PDX-1) fused to green fluorescent protein (GFP) capable of stable expression in fetal rat hepatic stem cells after transfection by electroporation.</p><p><b>METHODS</b>PDX-1 cDNA was amplified from SK900/BLSCRIPT plasmid and cloned into the multiple cloning site of pEGFP-C1 to obtain the recombined plasmid pEGFP-C1-PDX-1. Rat fetal hepatic stem cells were isolated, cultured, identified and transfected with the recombinant vector by electroporation, followed by observation of these cells with fluorescent microscope. The result of transfection was analyzed by RT-PCR and cell growth curve.</p><p><b>RESULTS</b>Identification by enzyme digestion confirmed successful construction of the recombinant vector. Fetal hepatic stem cells can stably express GFP and PDX-1 for a period of time, and their growth and proliferation was not obviously affected after transfection.</p><p><b>CONCLUSION</b>The fusion expression vector of EGFP-PDX-1 is successfully constructed and stably expressed in rat fetal hepatic stem cells, which may facilitate the study of the role of PDX-1 in stem cell differentiation into insulin-producing cells.</p>