Analysis of immune microenvironment and potential sensitive drugs in esophageal squamous cell carcinoma based on GEO database and bioinformatics method / 中国胸心血管外科临床杂志

@#Objective    To construct a prognostic model of esophageal squamous cell carcinoma (ESCC) based on immune checkpoint-related genes and explore the potential relationship between these genes and the tumor microenvironment (TME). Methods     The transcriptome sequencing data and clinical information of immune checkpoint genes of samples from GSE53625 in GEO database were collected. The difference of gene expression between ESCC and normal paracancerous tissues was evaluated, and the drug sensitivity of differentially expressed genes in ESCC was analyzed. We then constructed a risk model based on survival-related genes and explored the prognostic characteristics, enriched pathway, immune checkpoints, immune score, immune cell infiltration, and potentially sensitive drugs of different risk groups. Results    A total of 358 samples from 179 patients were enrolled, including 179 ESCC samples and 179 corresponding paracancerous tissues. There were 33 males and 146 females, including 80 patients≤60 years and 99 patients>60 years. 39 immune checkpoint genes were differentially expressed in ESCC, including 14 low expression genes and 25 high expression genes. Drug sensitivity analysis of 8 highly expressed genes (TNFRSF8, CTLA4, TNFRSF4, CD276, TNFSF4, IDO1, CD80, TNFRSF18) showed that many compounds were sensitive to these immunotherapy targets. A risk model based on three prognostic genes (NRP1, ICOSLG, HHLA2) was constructed by the least absolute shrinkage and selection operator analysis. It was found that the overall survival time of the high-risk group was significantly lower than that of the low-risk group (P<0.001). Similar results were obtained in different ESCC subtypes. The risk score based on the immune checkpoint gene was identified as an independent prognostic factor for ESCC. Different risk groups had unique enriched pathways, immune cell infiltration, TME, and sensitive drugs. Conclusion     A prognostic model based on immune checkpoint gene is established, which can accurately stratify ESCC and provide potential sensitive drugs for ESCC with different risks, thus providing a possibility for personalized treatment of ESCC.

Surgical management of sacral neurogenic tumors / 中国骨伤

OBJECTIVE@#To observe the efficacy and complications of one-stage tumor resection to treat primary sacral neurogenic tumors and to discuss some details in the clinically relevant anatomy.@*METHODS@#A retrospective analysis of 26 patients with neurogenic turors of the sacral spine who were surgically treated from January 2001 to January 2018, including 16 males and 10 females, aged from 21 to 69 years old with an average age of (39.3±10.9) years old. The courses of diseases ranged from 3 to 56 months with an average of (17.9±10.1) months. The diameters of presacral components ranged from 3.3 to 19.6 cm with an average of (8.7±4.1) cm. The proximal margin of presacral lesions was above the L5S1 level in 6 cases, and lower than L5S1 in 20 cases. A posterior incision approach for one-stage complete resection of the tumor was used firstly, and an anterior approach was combined when necessary. Spinal-pelvic reconstruction with the modified Galveston technique was also carried out in relevant cases. Whether to preserve the tumor-involved nerve roots depended on the situation during the operation. The operation time, intraoperative blood loss, pain relief, and complications were recorded. The lumbosacral spine stability and sacral plexus neurological function were evaluated during postoperative follow-up, and local recurrence and distant metastasis were examined as well.@*RESULTS@#Total excision was achieved in all 26 patients, with an operation time of (160.4±35.3) mins and an intraoperative blood loss of (1 092.3±568.8) ml. Tumors have been removed via a posterior-only approach in 21 cases and via combined anterior/posterior approaches in 5 cases. The diameter of presacral masses components ranged from 11.3 to 19.6 cm with an average of (15.1±3.2) cm in patients with combined anterior/posterior approaches, and ranged from 3.3 to 10.9 cm with an average of (7.2±2.4) cm in patients with a posterior-only approach. Five of the six patients whose proximal margin of presacral masses was above the L5S1 level adopted combined anterior/posterior approaches, and 20 patients lower than the L5S1 level adopted the posterior-only approach. All the patients were followed up for 6 to 82 months with an average of(45.4±18.2)months. Postoperative lumbosacral pain and lower extremity radicular pain were significantly relieved, and sensation, muscle strength and bowel and bladder function were also improved to varying degrees. The postoperative early complications included superficial wound infection in 1 case and cerebrospinal fluid leakage in 2 cases. Pathology confirmed 17 cases of schwannoma, 7 cases of neurofibroma and 2 cases of malignant schwannoma. Local recurrence was observed in two cases of benign neurogenic tumors. One patient with a malignant nerve sheath tumor had lung metastasis, who died 20 months after the operation. In 17 cases of upper sacral neurogenic tumors, 4 cases did not undergo spinal-pelvic reconstruction with internal fixation, of which 2 cases suffered from postoperative segmental instability. Tumor-involved nerve roots were resected during surgery in 7 cases. One of these patients who had S2 and S3 nerve roots sacrificed simultaneously had an impaired bladder and bowel function postoperatively, and did not recover completely. In the other 6 cases, the neurological function was not damaged obviously or recovered well.@*CONCLUSION@#The posterior approach can directly expose the lesions, and it is also convenient to deal with nerve roots and blood vessels. The operation time, intraoperative blood loss, degree of symptom relief, complication rate, and recurrence and metastasis rate can be controlled at an appropriate level. It is a safe and effective surgical approach. When the upper edge of the presacral mass is higher than the L5S1 level or the diameter of the presacral mass exceeds 10 cm, an additional anterior approach should be considered. The stress between the spine and pelvis is high, and internal fixation should be used to restore the mechanical continuity of the spine and pelvis during resection of neurogenic tumors of the high sacral spine. Most of the parent nerve roots have lost their function. Resection of a single parent nerve root is unlikely to cause severe neurological dysfunction, while the adjacent nerve roots have compensatory functions and should be preserved as much as possible during surgery.

Mechanism of Proteoglycan TPG-1 from Trametes robiniophila Inhibiting Growth of Human Hepatoma SK-HEP-1 Cells / 中国实验方剂学杂志

ObjectiveProteoglycan TPG-1 isolated from Trametes robiniophila（Huaier） has proved to have anti-hepatoma activity， and this paper aims to explore the molecular mechanism. MethodHuman hepatoma SK-HEP-1 cells were treated with TPG-1 （0， 0.05， 0.1， 0.25， 0.5， 1 g·L-1）. Then cell survival was detected by methyl thiazolyl tetrazolium （MTT） and apoptosis by flow cytometry. In addition， expression of genes in SK-HEP-1 cells treated with or without TPG-1 was examined by DNA microarray to preliminarily explore the anti-hepatoma molecular mechanism of TPG-1. ResultTPG-1 inhibited the proliferation of SK-HEP-1 cells as compared with the blank group （P<0.01）. After treatment with 1 g·L-1 TPG-1 for 48 h， the apoptosis rate of SK-HEP-1 cells increased （P<0.01）， and TPG-1 promoted the cleavage of cysteinyl aspartate specific proteinase （Caspase）-3 and Caspase-7， the key mediators of apoptosis （P<0.01）. Additionally， TPG-1 （1 g·L-1） suppressed the migration of SK-HEP-1 cells （P<0.05）. A total of 971 differentially expressed genes （DEGs） were identified in SK-HEP-1 cells after treatment with TPG-1， with 486 up-regulated and 485 down-regulated. These DEGs were mainly involved in the Gene Ontology （GO） terms of interleukin-6 （IL-6） biosynthesis， antigen processing and presentation， superoxide dismutase activity， positive regulation of mitogen-activated protein kinase kinase kinase （MAPKKK） cascade， nature killer （NK） cell chemotaxis， and chemokine biosynthesis， and the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways of nucleotide-binding oligomerization domain （NOD）-like receptor signaling pathway， apoptosis， Toll-like receptor signaling pathway， retinoic acid-inducible gene-Ⅰ （RIG-Ⅰ）-like receptor signaling pathway， T-cell receptor signaling pathway， and chemokine signaling pathway. Western blot results showed that TPG-1 （1 g·L-1） activated mitogen-activated protein kinase （MAPK） signaling pathway in SK-HEP-1 cells （P<0.01）. ConclusionProteoglycan TPG-1 inhibited the proliferation and migration， and induced apoptosis of human hepatoma SK-HEP-1 cells. Up-regulation of MAPK signaling pathway may be responsible for the growth inhibition of human hepatoma SK-HEP-1 cells by TPG-1.

Pathogen spectrum of viral encephalitis in children living in Hebei province, China from May to December 2017 / 中华实验和临床病毒学杂志

Objective@#To investigate the pathogenic characteristics of viral encephalitis in children living in Hebei province.@*Methods@#We randomly collected cerebrospinal fluid specimens from a total of 399 children diagnosed with viral encephalitis in Hebei Children′s Hospital from May to December 2017. Real-time fluorescence quantitative PCR and Sanger sequencing were used to detect viral nucleic acids in cerebrospinal fluid by an automatic laboratory station. Statistical analysis was performed on the experimental data using SPSS 21.0 software and the clinical data were analyzed. Comparison of infection rates of EV encephalitis in different months, using line × column chi-square test. The MRI and EEG positive rates of different viral encephalitis and viral encephalitis patients not infected with the virus were analyzed by Fisher′s exact probability test. The positive rate of infection with different viruses and non-virus agents was analyzed by Fisher′s exact probability test.@*Results@#The result showed that 80 of 399 samples were positive, and the positive rate was 20.05%. It included 22 cases of enterovirus, 4 cases of influenza A virus, 3 cases of mumps virus, 2 cases of herpes simplex virus type 1, 1 case of herpes simplex virus type 2, 4 cases of EB virus, 7 cases of cytomegalovirus, 7 cases of herpes zoster virus, 8 cases of adenovirus, 14 cases of human herpesvirus type 6. Eight cases had combined viral infection. Eight cases had concurrent infections: 3 cases had enterovirus and herpesvirus type 6 concurrent infection, 1 case had enterovirus and Japanese encephalitis virus concurrent infection and 1 case had herpes simplex virus type 2 and adenovirus, 1 case had influenza A virus herpesvirus type 6, 1 case had mumps virus and herpesvirus type 6, 1 case had mumps virus and herpesvirus type 6, 1 case had herpes simplex virus type 1 and herpes zoster virus concurrent infections. Children with EV viral encephalitis in Hebei Province were highly prevalent in May and June (P=0.016). HHV6 virus encephalitis was more susceptible to infection than non-HHV6 virus (P=0.016); The rate of MRI positive findings in patients with different viral encephalitis was not statistically significant (P>0.05). The result of EEG of different viral encephalitis were P>0.05, which was not statistically significant.@*Conclusions@#EV was the most common pathogen of children with viral encephalitis in Hebei province. Encephalitis caused by influenza A virus cannot be ignored in clinical practice.

Associations between physical activity, screen time and anxiety, sleep quality among Chinese college students / 中国学校卫生

Objective@#To explore associations between physical activity, screen time and anxiety, sleep quality among college students in Shanghai, and to provide a reference for relevant prevention and control.@*Methods@#By using cluster random sampling method, a total of 4 964 students from grade 1 to grade 2 in 3 universities from 3 districts of Shanghai were enrolled. Self-Rating Anxiety Scale, Pittsburgh Sleep Quality Index and International Physical Activity Questionnaire were used to assess the level of anxiety, sleep quality and physical activity.@*Results@#The reporting rate of anxiety symptoms among students was 9.7%(8.7% for males and 11.4% for females) and the prevalence of poor sleep quality was 55.0%(51.8% for males and 60.4% for females), there was significant gender differences in anxiety symptoms and poor sleep quality rate(χ2=9.92, 34.81, P<0.01). Among male students, with adjustment of age, BMI and lifestyle, those who met neither physical activity nor screen time recommendations had 2.23(95%CI=1.31-3.79) and 1.48(95%CI=1.13-1.94) times risks for anxiety and poor sleep quality than those meeting both recommendations. Among girls, there was a significant association between screen time and anxiety(aOR=1.61, 95%CI=1.18-2.21). However, physical activity was not associated with anxiety and sleep quality.@*Conclusion@#High screen time and physical inactivity may increase the risk of anxiety and poor sleep quality among male college students, and screen time may also increase the risk of anxiety among female college students.

Observation on time-effect for the stimulating at Zusanli (ST 36) with minimally invasive embedding with PGLA in the healthy person / 中国针灸

OBJECTIVE@#To explore the objectivity and time-effect of stimulating effect at acupoint with PGLA in the healthy person, and to provide a basis for the rational interval of minimally invasive embedding of PGLA.@*METHODS@#Before embedding, 8 h, 3rd, 7th, 10th, 14th day after embedding, medical imaging magnetic resonance imaging (MRI) scanning technique was used to collect local T2WI pressure-lowering and T2-Mapping 8 echoes sequence image of left Zusanli (ST 36) in 8 cases of healthy person. The T2-Mapping 8 echoes sequence image was generated by the relevant software to the T2-Mapping image and the local T2 value was measured. The characteristics of local T2WI pressure-fat image signal intensity and the change of T2 value at left Zusanli (ST 36) with minimally invasive embedding with PGLA were observed and analyzed.@*RESULTS@#①There was no abnormal signal on the T2WI pressure-fat image on the left Zusanli (ST 36) point before the embedding. The high-signal was seen on the local T2WI pressure-fat image at each time point after embedding, there was no significant difference in local signal intensity between 8 h, 3rd and 7th day after embedding. The local signal intensity decreased on the 10th day after embedding, and the local signal intensity decreased significantly on the 14th day after embedding.②The T2 value at each time point after embedding increased significantly compared with that before embedding (all 0.05); there was no significant difference between the T2 value on the 7th and the 10th day after embedding (>0.05)，the T2 value on the 14th day after embedding was significantly lower than that on the 7th day after embedding (<0.01).@*CONCLUSION@#It has a stimulating effect on the local acupoints with minimally invasive embedding with PGLA in the healthy person, and the stimulating effect has certain time-effect. The effective stimulation time is about 2 weeks. The rational interval period for the minimally invasive embedding with the PGLA of the same specification type should be about 2 weeks.

Research on network pharmacology of Acori Tatarinowii Rhizoma combined with Curcumae Radix in treating epilepsy / 中国中药杂志

The chemical constituents and action targets of Acori Tatarinowii Rhizoma and Curcumae Radix were screened by network pharmacological method,and the mechanism of the combination of Acori Tatarinowii Rhizoma and Curcumae Radix in the treatment of epilepsy was analyzed. All chemical constituents of Acori Tatarinowii Rhizoma and Curcumae Radix were retrieved by TCMSP,and their action targets were screened. Component target PPI network was constructed. Epilepsy-related genes were retrieved from PharmGkb database,and PPI networks of disease targets were drawn by Cytoscape software. Cytoscape software was used to merge the network,screen the core network,and further analyze the gene GO function and KEGG pathway enrichment,which was verified by experimental research. One hundred and five chemical constituents of Acori Tatarinowii Rhizoma and 222 chemical constituents of Curcumae Radix were retrieved. Nineteen compounds were selected as candidate compounds according to OB and DL values. Among them,4 chemical constituents of Acori Tatarinowii Rhizoma and 15 chemical constituents of Curcumae Radix were found. A total of 88 target proteins were retrieved by retrieving TCMSP data,and PPI network was constructed. Through PharmGkb database,29 epilepsy-related genes were retrieved and disease target network was established. Cytoscape software and plug-ins were used for network merging and core network screening,and 69 genes were screened out. Through GO function analysis and KEGG pathway analysis,the mechanism of anti-epilepsy is related to prolactin signaling pathway,HTLV-Ⅰ infection signaling pathway,MAPK signaling pathway and herpes simplex infection signaling pathway. Further experimental verification showed that the serum prolactin level in epileptic rats was significantly increased. The neurons in hippocampal CA1 area degenerated,necrotized and lost 24 hours after epileptic seizure,and some neuron interstitial edema occurred. The possible mechanism of compatibility of Acori Tatarinowii Rhizoma and Curcumae Radix is related to serum prolactin level,MAPK signaling pathway,HTLV-Ⅰ infection and herpes simplex infection. The analysis may be related to viral encephalitis caused by HTLV-Ⅰ virus and herpes simplex infection,which damages nerve cells and causes seizures.

Mechanism of Acori Tatarinowii Rhizoma-Curcumae Radix treating depression based on network pharmacology / 中国中药杂志

To screen the target for the treatment of depression of Acori Tatarinowii Rhizoma and Curcumae Radix using the pharmacological method of network pharmacology, in order to define the mechanism of antidepressant effect. Pharmacological data (TCMSP) of forall of chemical constituents of Acori Tatarinowii Rhizoma and Curcumae Radix through traditional Chinese medicine system (TCMSP) was retrieved to screen the target sites, and construct the component target PPI network. PharmGkb database was retrieved for the genes associated with depression, and the disease target was mapped using the Cytoscape software. The Cytoscape software was used to merge the network and filter the core network, and further analyze the gene GO function and the KEGG pathway enrichment. There were 62 nodes and 87 connections on the target PPI network. The PPI network had 1 289 nodes and 17 714 connections. After the network merged, the component-target-disease network had 1 337 nodes and 17 801 connections. Through screening the core network, there were 63 nodes and 935 connections, which represented the complex interaction between the components and the target. Gene GO functional analysis suggested that biological processes, molecular functions and cell components were involved. Gene KEGG pathway enrichment analysis showed associations with misfolded protein, secretory hormone secretion, and apoptosis of hippocampal neurons. The possible mechanism for treating depression is the adjustment of wrong folding protein, sex hormone secretion and apoptosis of hippocampal neurons.

Effect of different shear stress on the expression of IL-8 and ET-1 in vascular endothelial cells / 中国医师杂志

Objective To investigate the effect of different shear stress on the expression of Interleukin-8 (IL-8) and endothelin-1 (ET-1) in vascular endothelial cells.Methods Umbilical vein endothelial cell line (ECV-304) was used as the research cell.The shear stress of 5 dyne/cm2 and 10 dyne/cm2 was regulated by the self-made shearing stress control device.The shear stress in were maintained at 0,5 dyne/cm2 and 10 dyne/cm2 respectively in the control group,the low shear stress group and the high shear stress group.The effects on the levels of IL-8 and ET-1 were analyzed between the three groups at five time points of 30 min,60 min,120 min,300 min,420 min.Pearson correlation analysis was used to analyze the correlation between IL-8 and ET-1.Results The level of IL-8 in the three groups has been on the rise.At the three time points of 30 min,60 min and 120 min,there was no statistically significant difference in IL-8 level between the three groups (P ＞ 0.05).At the two time points of 300 min and 420 min,the difference of the IL-8 level in the three groups was statistically different (P ＜ 0.05),At the two time points of 300 min and 420 min,the IL-8 level in the low shear stress group was higher than that in the control group and the high shear group,the IL-8 level in the high shear group was higher than that in the control group (P ＜ 0.05).The level of ET-1 in the control group and the low shear group showed an upward trend,and the ET-1 level in the high shear group increased continuously in the former 120 min,but began to decrease continuously since then.At the three time points of 30 min,60 min and 120 min,the difference of the ET-1 level in the three groups was statistically different (P ＜ 0.05).The ET-1 level of the high shear group at three time points of 30 min,60 min and 120 min was higher than that of the control group,the level of ET-1 at two time points of 30 min and 60 min was higher than that in low shear stress group (P ＜ 0.05),the ET-1 level of the low shear group at two time points of 60 min and 120 min was higher than that of the control group (P ＜ 0.05).At the two time points of 300 min and 420 min,there was no significant difference in the level of ET1 between the three groups (P ＞ 0.05).Pearson correlation analysis showed that there was a positive correlation between the expression of IL-8 and ET-1 (r =0.384,P =0.031).Conclusions Shear stress can affect the expression of IL-8 and ET-1 in vascular endothelial cells,the shear stress of 5 dyne/em2 can increase the level of IL-8 more efficiently,the shear force of 10 dyne/cm2 can increase the level of ET-1 more obviously,but it may cause damage to the vascular endothelial cells.

Effect of miR-24 on chemotherapy sensitivity in lung cancer A549 cells / 中国病理生理杂志

AIM:To study the effect of microRNA (miR)-24 on chemotherapy sensitivity and its possible mechanisms in human lung adenocarcinoma A549 cells. METHODS:The expression of miR-24 in the A549 cells and A549/DDP cells was determined by real-time PCR. Transfection of miR-24 inhibitor was used to down-regulate the miR-24 level in the A549/DDP cells. The viability and apoptosis rate were measured by CCK-8 assay and flow cytometry, respec-tively. The protein levels of Bcl-2, Bax, cleaved caspase-3, cleaved caspase-9, cytochrome C (Cyt C), phosphorylated extracellular signal regulated kinase (p-ERK) and P53 were detected by Western blot. Luciferase reporter assay was used to predict and identify the target genes of miR-24. RESULTS:The expression of miR-24 was significantly higher in the A549/DDP cells than that in the A549 cells (P<0.05). miR-24 inhibitor induced cell apoptosis and increased the sensi-tivity of the A549/DDP cells to cisplatin. Furthermore, miR-24 inhibitor down-regulated the ratio of Bcl-2/Bax, while up-regulated the protein levels of P53, p-ERK, cleaved caspase-9, cleaved caspase-3 and Cyt C. Incubation with U0126, a specific ERK inhibitor, partly reversed the viability of miR-24 inhibitor transfected A549/DDP cells. Bioinformatics analy-sis demonstrated that p53 was a potential target gene of miR-24. Co-teansfection of miR-24 inhibitor and P53 siRNA in A549/DDP cells partially reversed the effect of miR-24 inhibitor on cell viabiltiy. CONCLUSION:Down-regulation of miR-24 increases the sensitivity of A549/DDP cells to cisplatin. The mechanism may be related to directly targeting p53 gene and over-activation of ERK/P53 signaling pathway, thus promoting apoptosis via mitochondrial apoptosis pathway.

Relationships between differences in tumorigenicity and immunogenetic backgrounds of nude mice / 中华微生物学和免疫学杂志

Objective To study the relationships between differences in tumorigenicity and immu-nogenetic backgrounds of nude mice. Methods According to the Chinese Pharmacopoeia, positive and neg-ative groups were set up in both Laboratory A and B with ten nude mice in each group. Organ tissues were collected for clinicopathological analysis. Blood samples were collected and detected using flow cytometry. DNA was extracted and analyzed with 23 STR markers. Results The positive group of Laboratory B was in-valid (7/10 tumor formation). The two laboratories showed no significant difference in the results of patho-logical analysis, but had significant differences in CD25, CD8, CD4, Th1 and Th2. There were 13 and 18 polymorphic sites respectively found in nude mice of Laboratory A and B. Further analysis of the non-tumor-bearing nude mice in Laboratory B positive group revealed that CD25, Th2, D3Mit29 and D5Mit48 were the specific indexes. Conclusion Differences in tumorigenicity might be related to the diversity of immunoge-netic backgrounds of nude mice.

Lung cancer with concomitant double gene mutation

A patient presenting with concomitant epidermal growth factor receptor [EGFR] mutation and anaplastic lymphoma kinase [ALK] translocation is very rare. We report a non-small cell lung cancer [NSCLC] patient with concomitant EGFR [exon 19-del] mutation and ALK rearrangement. The positron emission tomography-computed tomography [PET-CT] scan revealed a highly metabolic mass lesion in the left lower lobe, measured 5.0 cm in the largest dimension in the S6 segment. Transbronchial lung biopsy [TBLB] showed the pathological diagnosis of invasive adenocarcinoma. Thus, the patient underwent left lower lobectomy and hilar-mediastina lymph node dissection [pT2N0M0]. The tumor harbor an ALK [D5F3 +] rearrangement and EGFR [exon 19-del] mutation. The patient initially received four cycles of chemotherapy [pemetrexed and carboplatin], and achieved partial response [PR]

Marked response to icotinib in lung squamous cell carcinoma with EGFR wild-type

We present a case of a 72-year male with primary lung squamous cell carcinoma without an epidermal growth factor receptor [EGFR] gene mutation that exhibited a lasting efficacy to icotinib treatment. Originally, the patient was treated with GP regimen for 2 cycles, local lesion radiotherapy [DT46Gy/2Gy*23F], and TP regimen for 2 cycles, with efficacy evaluation as stable disease [SD]. The condition was stable for 10 months until the fifth lumbar metastasis was discovered by emission computed tomography [ECT] in July 2015, and the pulmonary metastasis increased. Icotinib was administered at 125 mg orally three times per day. Chest computed tomography [CT] scan showed the tumor was in partial response [PR] and the PR lasted for 27 months

Synthetic study of vonoprazan fumarate / 国际药学研究杂志

Objective To develop a practical synthetic process of vonoprazan fumarate with high-yield and lower impurities to meet the quality requirements. Methods By using 5-(2-fluorophenyl)pyrrole-3-carboxaldehyde as the starting material,the qualified vonoprazan fumarate was synthesized via the following steps:①N-sulfonylation and the chloride impurity was removed by recrystalli-zation from MeOH;②the aldehyde was converted to amine by reductive amination,followed by forming the vonoprazan chloride to re-move the dimethylamino impurity;③vonoprazan free base was obtained by neutralization and then converted to fumarate at room tem-perature and finally recrystallized from MeOH/H2O(1:1). Results An impurity controllable synthetic process was developed with a 4％total yield improving. The final product was confirmed by ESI-MS and 1H NMR. Conclusion The synthetic process with single im-purity less than 0.1％and purity above 99.5％was obtained and suitable for scale production of vonoprazan fumarate.

Investigation of the effects induced by 1 400 W on nasopharyngeal carcinoma cell and the mechanism / 中国医师杂志

Objective To investigate the effect induced by specific inducible nitric oxide synthase (iNOS) inhibitor 1 400 W on nasopharyngeal carcinoma CNE-2 cells lines and its mechanism.Methods CNE-2 cells were treated by different concentrations of 1 400 W,diamminedichloroplatinum (DDP),and both chemicals.Cell counting kit-8 (CCK-8) was used to examine the viability of cells.Quantitative realtime polymerase chain reaction (qRT-PCR) was applied to detect the iNOS mRNA expression.Results The expression of iNOS mRNA was down-regulated by 1400W and was positively correlated with inhibitionrate of cell proliferation.1 400 W inhibits proliferation of CNE-2 cell in a concentration-dependent manner.The proliferation inhibition rate of CNE-2 cells treated by 1 400 W combined with DDP was not enhanced.Conclusions Specific inducible nitric oxide synthase inhibitor 1 400 W can exerts anti-tumor effect though inhibiting the expression of iNOS mRNA;The mechanism of chemosensitization induced by iNOS inhibitor on CNE-2 cells may be closely related level of down-regulation of iNOS expression.

Analysis of clinicopathological features and prognosis of 87 low grade glioma / 中国医师进修杂志

Objective To investigate the clinicopathological features and prognostic factors in patients with low grade glioma. Methods Eighty- seven patients with low grade glioma confirmed by cytological examination were retrospectively analyzed. Results Among 87 patients, male accounted for 62.1%(54/87), and the average age was 36.2 years. The average followed- up time was 51.4 months (3-135 months), and 5 cases were lost in follow-up. The follow- up rate was 94.3% (82/87). The 3- year survival rate was 84.1%, and the 5- year survival rate was 66.7%. The 3- year survival rate was related to clinical symptoms, maximum diameter of tumor and the extent of resection (P<0.01 or<0.05);and the 5- year survival rate was related to years, Karnofsky score, clinical symptoms, maximum diameter of tumor, the pathology classification and extent of resection (P<0.05 or<0.01). Conclusions Low grade glioma is more common in male patients and patients under the age of 40 years. Age below 40 years, Karnofsky score ≥ 70 scores, only epilepsy symptom, tumor diameter below 6.0 cm, oligodendrogliomas, complete resection or subtotal resection are positive prognostic factors. Postoperative radiotherapy can reduce the rate of tumor progression.

Nedaplatin-induced arrhythmia: retrospective analysis of three cases

Nedaplatin [NDP] is a second-generation platinum derivative that was developed in Japan. Nowadays, it is being widely used in the management of lung cancer, esophageal cancer, head and neck cancers, especially when cisplatin and carboplatin cannot be tolerated or show drug resistance. To the best of our knowledge, there are few reported cases of NDP-induced bradycardia in the relevant medical literature. The current report presents three patients treated with NDP chemotherapy-induced serious arrhythmias. The three cases developed sinus tachycardia and atrial premature beats, complete left bundle branch block, and bigeminy ventricular premature contraction, in the second, sixth and second cycle, respectively. No one died of cardiac toxicity. These were treated with dexamethasone, 5 mg intravenous injection and diphenhydramine 20 mg, intramuscular injection. The heart rhythm returned to normal in 30 minutes, a day, and four days, respectively

Therapeutic Observation of Herb-partitioned Umbilicus Fumigation for Uterine Descent / 上海针灸杂志

Objective To observe the clinical efficacy of herb-partitioned umbilicus fumigation in treating uterine descent. Method Forty patients diagnosed with uterine descent were randomized into two groups. Twenty subjects in the treatment group were intervened by herb-partitioned umbilicus fumigation, while 20 subjects in the control group were by biofeedback electrical stimulation. The therapeutic efficacy was evaluated 2 months later. Result The total effective rate was 90.0%in the treatment group versus 80.0%in the control group. Conclusion The two methods both can produce a content therapeutic efficacy in treating uterine descent, while the treatment group is superior to the control group.

Follow-up research and dosage correlation analysis in patient with clopidogrel hypo-responsiveness after percutaneous coronary intervention / 中国介入心脏病学杂志

Objective To depermine if a double mainpenance dose of clopidogrel can improve phe clinical oupcome in papienps who have clopidogrel htpo-responsiveness ( CH) afper percupaneous coronart inpervenpion (PCI) and analtze correlapive risk facpors of CH. Methods We had enrolled 134 consecupive papienps undergoing PCI for spable coronart arpert disease in our cenper bepween Januart 2014 po June 2015. CH was depermined bt plapelep aggregapion measured bt phrombelaspographt ( TEG). Blood samples were paken 24 h and 3 monphs afper PCI procedure. All subjecps were divided inpo 2 groups (i. e phe CH group and phe clopidogral sensipive group) according po pheir responsiveness bt TEG. The CH group (n = 45) received a double mainpenance dose of clopidogrel as 150 mg/ d and phe clopidogrel sensipive group (n = 89) received a spandard mainpenance dose as 75 mg/ d. Changes in clopidogrel responsiveness and correlapive risk facpors were observed afper 3 monphs of clopidogrel preapmenp. Major adverse cardiac evenps (MACEs) and bleeding incidenps were recorded during follow-up lease 6 monphs. Results The clopidoprel htpo-responsive rape decreased from 33. 6% (45 / 134 papienps) po 11. 9% (16 / 134 papienps) afper 3 monphs of preapmenp. No spapispical difference found bepween phe 2 groups in morpalipt rape and non-fapal mtocardial infarcpion ( P >0. 05). Rapes of overall MACE (33. 3% vs. 22. 5% ), rehospipalizapion (26. 7% vs. 16. 9% ) and pargep vessel revascularizapion (11. 1% vs. 6. 7% ) were significanp higher in phe CH group ( all P < 0. 05) . Mulpivariape regression analtsis showed: smoking ( OR 4. 498, 95% CI 1. 378 - 4. 018, P = 0. 036), diabepes (OR 4. 385, 95% CI 1. 370 - 7. 552,P = 0. 026) and clopidogrel dosage ( OR 0. 597, 95% CI 1. 005 - 2. 676, P = 0. 019 ) were phe risk facpors for CH. Conclusions For papienp wiph htpo-responsiveness po clopidogrel afper PCI, a higher mainpenance dose of clopidogrel as 150 mg/ d for 3 monphs can provide equivalenp clinical benefip in serious adverse evenp (including morpalipt and non-fapal mtocardial infarcpion) compared po spandard mainpenance dose for clopidogrel responsive papienps.

Genetic monitoring and analysis of highly immunodeficient mice from different sources by microsatellite DNA markers / 中国比较医学杂志

Objective To test and analyze the genetic background of highly immunodeficient mice from different sources.Methods Four highly immunodeficient mouse strains from different sources of NOD background were collected. 30 microsatellite DNA sites were detected, and the genotype can be displayed by gel electrophoresis and STR scanning. Results 17 microsatellite sites exhibit polymorphism in 20 mice of the four groups.There were 30 homozygous loci in the mice of groups A and B, and heterozygous in the other two groups.The genetic distance is minimum between groups A and B, showing a higher genetic similarity.Conclusions The genetic backgrounds are different in highly immunodeficient mice from different sources.