Regulatory Mechanism of Mangiferin Combined with Bortezomib on Malignant Biological Behavior of Burkitt Lymphoma and Its Effect on Expression of CXC Chemokine Receptors / 中国实验血液学杂志

OBJECTIVE@#To analyze the effects of mangiferin combined with bortezomib on the proliferation, invasion, apoptosis and autophagy of human Burkitt lymphoma Raji cells, as well as the expression of CXC chemokine receptors (CXCRs) family, and explore the molecular mechanism between them to provide scientific basis for basic research and clinical work of Burkitt lymphoma.@*METHODS@#Raji cells were intervened with different concentrations of mangiferin and bortezomib alone or in combination, then cell proliferation was detected by CCK-8 assay, cell invasion ability was detected by Transwell chamber method, cell apoptosis was detected by Annexin V/PI double-staining flow cytometry, apoptosis, autophagy and Akt/mTOR pathway protein expression were detected by Western blot, and the expression changes of CXCR family was detected by real-time quantitative PCR (RT-qPCR).@*RESULTS@#Different concentrations of mangiferin intervened Raji cells for different time could inhibit cell viability in a concentration- and time-dependent manner (r =-0.682, r =-0.836). When Raji cells were intervened by combination of mangiferin and bortezomib, compared with single drug group, the proliferation and invasion abilities were significantly decreased, while the apoptosis level was significantly increased (P <0.01). Mangiferin combined with bortezomib could significantly up-regulate the expression of pro-apoptotic protein Bax and down-regulate the expression of anti-apoptotic protein Bcl-2 after intervention in Raji cells. Caspase-3 was also hydrolyzed and activated, and then induced the apoptosis of Raji cells. Mangiferin combined with bortezomib could up-regulate the expression of LC3Ⅱ protein in Raji cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P <0.01). Mangiferin combined with bortezomib could significantly inhibit the phosphorylation levels of Akt and mTOR, inhibit the proliferation and invasion of Raji cells by inhibiting Akt/mTOR pathway, and induce cell autophagy and apoptosis. Mangiferin and bortezomib could down-regulate the expressions of CXCR4 and CXCR7 mRNA after single-agent intervention in Raji cells, and the down-regulations of CXCR4 and CXCR7 mRNA expression were more significant when the two drugs were combined (P <0.01). Mangiferin alone or combined with bortezomib had no significant effect on CXCR5 mRNA expression in Raji cells (P >0.05), while the combination of the two drugs could down-regulate the expression of CXCR3 (P <0.05).@*CONCLUSION@#Mangiferin combined with bortezomib can synergistically inhibit the proliferation and invasion of Raji cells, and induce autophagy and apoptosis. The mechanism may be related to the inhibition of Akt/mTOR signaling pathway, down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, and the inhibition of the expression of CXCR family.

Study on untargeted metabolomics of Codonopsis pilosula from different producing areas based on ultra-performance liquid chromatography tandem high resolution mass spectrometry / 药学学报

Lu Dangshen, a traditional authentic medicinal material of Codonopsis Radix is mainly produced in Shangdang (Changzhi) area of Shanxi Province. Baitiao Dangshen is mainly produced in Gansu Province. Codonopsis Radix contains many kinds of components such as phenylpropanoids, polyalkynes, alkaloids, terpenes, fatty acids, flavonoids, and so on. At present, the effect of producing areas on its chemical compositions has not been systematically studied. This study analyzed the differences of metabolites among Codonopsis pilosula from different producing areas by UPLC-HRMS. PCA, OPLS-DA coupled with Thermo mzcloud online and local databases were used to compare the overall differences of metabolites among Codonopsis pilosula from different producing areas, and the chemical constituents were identified to further screen and find out the different metabolites and analyze the metabolic pathways by information retrieval in HMDB, PubChem, Chemspider and KEGG databases. The results showed that 72 differential metabolites were identified in this study. There were 15 kinds of up-regulated and 57 kinds of down-regulated metabolites of Lu Dangshen compared with Baitiao Dangshen. The top 30 metabolic pathways were analyzed by KEGG enrichment, and the most important metabolic pathways were phenylpropanoid biosynthesis, which was demonstrated that phenylpropanoid biosynthesis pathway and related intermediate metabolites could be used as the characteristics of distinguishing Lu Dangshen from different habitats of Codonopsis pilosula. The present study provided a basis for analyzing the influence of producing areas on the chemical components of Codonopsis pilosula and reasonably evaluating the quality of Codonopsis Radix, and also provided a new idea for expounding the authenticity of Lu Dangshen.

Study on transfusion-related acute lung injury caused by HLA-Ⅱ antibody / 中国输血杂志

【Objective】 To explore the risk factors of transfusion-related acute lung injury (TRALI). 【Methods】 The clinical symptoms, signs, imaging examinations, and laboratory test results of two patients with TRALI after blood transfusion were retrospectively analyzed, and human leukocyte antigen (HLA) genotyping of the patient and HLA antibodies typing of the plasma donors were performed. 【Results】 The clinical manifestations and laboratory parameters of two patients were consistent with those of TRALI after blood transfusion. After timely clinical respiratory support treatment, all patients were improved. Blood donors produced high titers of HLA-Ⅱ antibodies after pregnancy, including antibodies that specifically recognize the patient′s HLA antigen. 【Conclusion】 Two patients developed TRALI after platelet transfusion from a female blood donor, which was caused by HLA-Ⅱ antibodies.

Study on RHD and RHCE gene mRNA based on three generation sequencing technology / 中国输血杂志

【Objective】 To establish RH gene mRNA sequencing method based on nanopores sequencing and to explore the RHD and RHCE mRNA transcripts in D positive and Del individuals. 【Methods】 From March 2021 to May 2022, 5 RhD positive samples and 5 Del samples screened out by hospitals in Chengdu were sent to our laboratory for futher examination. The erythrocytes and buff coat were isolated, then DNA and RNA were extracted.All 10 samples were genotyped by PCR-SSP. After the mRNA was reversely transcribed into cDNA, the full-length mRNA of RHD and RHCE genes were simultaneously amplified by a pair of primers. Sanger sequencing and third-generation sequencing technology based on Nanopore were used to sequence the amplified products, and the types and expressions of different splices of RHD and RHCE gene mRNA transcripts were analyzed. 【Results】 The method established in this study can simultaneously amplify the full length transcripts of RHD and RHCE. Ten different RHD gene mRNA transcripts and nine RHCE gene mRNA transcripts were detected in 10 samples. RHD full-length transcript (RHD-201) can be detected in RhD Del type, but the expression amount was significantly lower than that in RhD positive samples. The expression amount of transcript RHD-207 (Del789) in Del samples was significantly higher than that in RhD positive samples. The transcript RHD-208 (Del8910+ 213) was only detected in RhD Del type individuals, and no significant difference was found between other RHD transcripts and all RHCE transcripts in the two phenotypes. 【Conclusion】 In this study, an analytical method for sequencing full-length transcript isomers of RHD and RHCE mRNA via the third generation was successfully established, and complex alternative splicing patterns were found in RHD and RHCE genes, providing a new method for the study of alternative splicing of blood group gene variants mRNA.

Application status and research progress in perioperative chemoradiotherapy for T 3 rectal cancer / 中华放射肿瘤学杂志

T 3 rectal cancer patients are a heterogeneous group of populations. T 3 stage patients with good prognosis are similar to their T 2 stage counterparts, and T 3 stage patients with poor prognosis are similar to T 4 stage counterparts. Although small sample clinical trials, meta-analyses and retrospective analyses have been conducted, clinical guidelines are not completely consistent with the definition of risk factors and treatment recommendations for this group of populations. At present, the treatment strategy for T 3 rectal cancer is still controversial, especially the application of perioperative radiotherapy. In this article, current application status and research progress in perioperative chemoradiotherapy for T 3 rectal cancer were reviewed.

Current status of treatment for locally advanced middle-low rectal cancer with lateral lymph node metastasis / 中华放射肿瘤学杂志

The incidence of lateral lymph node metastases (LLN) of locally advanced middle-low rectal cancer (II-Ⅲ stage) is high and clinical prognosis is poor. At present, the treatment plan of LLN is controversial between the East and the West. Scholars from the East represented by Japan believe that LLN is a regional disease. Lateral pelvic lymph node dissection (LPLND) is recommended when the tumor is located under the peritoneal reflection and invades into the muscular layer, regardless of the presence or absence of LLN. However, European and American scholars believe that LLN is a systemic disease and recommend neoadjuvant chemoradiotherapy (nCRT) combined with total mesorectal excision (TME). Nevertheless, recent studies have found that neither nCRT nor LPLND can significantly reduce the locoregional recurrence (LR) rate in patients with LLN, while nCRT combined with LPLND yields better prognosis. Some studies have also demonstrated that increasing the radiotherapy dose of metastatic lymph nodes can improve the local control rate. In this article, current treatment status of this population was reviewed, aiming to provide a basis for clinical treatment.

The polymorphism of HPA-1-6w, HPA-15 and HPA-32bw-35bw in platelet donors from Deyang, Sichuan / 中国输血杂志

【Objective】 To explore the polymorphism of HPA-1-6w, HPA-15 and 32bw-35bw in platelet donors in Deyang, Sichuan, and estimate whether to include the detection of 32bw-35bw in the platelet bank. 【Methods】 Polymerase chain reaction with sequenced based typing (PCR-SBT) was used to sequence the HPA-1-6w, HPA-15 and 32bw-35bw loci of 205 platelet donors in Deyang. Allele frequencies were calculated by the direct counting method. The frequencies of HPA-1-6 and 15 alleles in northern and southern Chinese, Japanese and Australian population were compared, and those HPA loci and HPA-32bw-35bw were searched in the Chinese Millionome Database (CMDB) and genomAD to obtain the polymorphism data. Then the Chi-square test was performed with the data of this study through GraphPad Prism 9 software. 【Results】 The allele frequencies of HPA-1b, 2b, 3b, 5b, 6bw and HPA-15b were 0.005(2/410), 0.037(15/410), 0.471(193/410), 0.020(8/410), 0.010(4/410) and 0.461(189/410), respectively, b allele of HPA-32bw-35bw and HPA-4 was not detected. Statistical significance was observed between the HPA-1b allele frequency of this study and northern Chinese, Australian population and genomAD global population sample (P< 0.05, 0.005 vs 0.014 vs 0.145 vs 0.122). The frequency of HPA-2b alleles in this study, Japanese population and genomAD global population samples was 0.037 vs 0.120 vs 0.100, with statistical difference(P<0.05). Comparison of HPA-5b and HPA-6bw allele frequencies with those of genomAD global population showed a statistical difference (P<0.05, 0.020 vs 0.089 and 0.010 vs 0.000 008, respectively). 【Conclusion】 The polymorphisms of HPA-1-6w and HPA-15 of donors in Deyang has characteristics of the southern Chinese. The frequencies of HPA-32bw-35bw were extremely low, which could be excluded from the platelet bank in Deyang.

Comparison of the Prognostic Value of Platelet-Related Indices in Biliary Tract Cancer Undergoing Surgical Resection / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Platelet-related indices, including mean platelet volume (MPV) and plateletocrit (PCT), have been reported as new prognostic factors of overall survival (OS) in many cancers, but not yet in biliary tract cancer (BTC). We intended to assess these indices in predicting OS in BTC patients with the aim to build a new prognostic model for patients with BTC after surgical resection. @*Materials and Methods@#Survival analysis and time receiver operating characteristic analysis were applied to screen the platelet indices. Univariate and multivariate Cox analyses were used to identify independent prognostic factors and develop a new prognostic model. Harrell’s C-statistics, calibration curves, and decisive curve analysis were used to assess the model. @*Results@#MPV and platelet distribution width (PDW)/PCT showed the best prognostic accuracy among the platelet indices. In multivariable analysis, factors predictive of poor OS were presence of nodal involvement, Non-radical surgery, poor tumor differentiation, carbohydrate antigen 19-9 > 100 U/mL, MPV > 8.1 fl, and PDW/PCT > 190. The new model was found to be superior to the TNM staging system and our new staging system showed higher discriminative power. @*Conclusion@#MPV and PDW/PCT have high prognostic value in BTC patients, and the novel staging system based on these two indices showed good discrimination and accuracy compared with the American Joint Committee on Cancer 7th TNM staging system.

Double Tract Reconstruction Reduces Reflux Esophagitis and Improves Quality of Life after Radical Proximal Gastrectomy for Patients with Upper Gastric or Esophagogastric Adenocarcinoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The aim of the present study was to compare the difference between double tract reconstruction and esophagogastrostomy. @*Materials and Methods@#Patients who underwent radical proximal gastrectomy with esophagogastrostomy or double tract reconstruction were included in this study. @*Results@#Sixty-four patients were included in this study and divided into two groups according to reconstruction method. The two groups were well balanced in perioperative safety and 3-year overall survival (OS). The rates of postoperative reflux esophagitis in the double tract reconstruction group and esophagogastrostomy group were 8.0% and 30.8%, respectively (p=0.032). Patients in the double tract reconstruction group had a better global health status (p < 0.001) and emotional functioning (p < 0.001), and complained less about nausea and vomiting (p < 0.001), pain (p=0.039), insomnia (p=0.003), and appetite loss (p < 0.001) based on the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire. Regarding the EORTC QLQ-STO22 questionnaire, patients in the double tract reconstruction group complained less about dysphagia (p=0.030), pain (p=0.008), reflux (p < 0.001), eating (p < 0.001), anxiety (p < 0.001), dry mouth (p=0.007), and taste (p=0.001). The multiple linear regression analysis showed that reconstruction method, postoperative complications, reflux esophagitis, and operation duration had a linear relationship with the global health status score. @*Conclusion@#Double tract reconstruction could better prevent reflux esophagitis and improve quality of life without scarifying perioperative safety or 3-year OS.

Pharmacokinetics of the main components differing between Ligustri Lucidi Fructus and its wine-steamed product / 药学学报

A quantitative analysis method for ten principal components (phenylethanol, iridoids and triterpenes) of raw Ligustri Lucidi Fructus and its wine-steamed product was developed using liquid chromatography tandem triple quadrupole mass spectrometry (LC-QQQ-MS) to study their pharmacokinetic behavior in vivo. The results of methodological investigation were in accord with the criteria of biological analysis. After a single administration to rats of the water extracts of Ligustri Lucidi Fructus and its wine-steamed product, the plasma concentration of each component at different time points was measured and the pharmacokinetic parameters were determined. The AUC0-24 h and Cmax of the phenylethanol components (salidroside, tyrosol, hydroxytyrosol) were the greatest, suggesting that these components are the main pharmacological substances of Ligustri Lucidi Fructus. In addition, the tmax values of the eight major components were even lower with administration of the wine-steamed product, suggesting that these components are rapidly absorbed. However, the tmax values of specnuezhenide and oleanolic acid were greater with administration of the wine-steamed product, indicating that these two components were more slowly absorbed. A secondary peak phenomenon of tyrosol and hydroxytyrosol were observed in two sample groups, whereas the secondary peak phenomenon of salidroside occurred only with the wine-steamed product. This result suggests that the effect of wine-steamed product could persist for a long period. Meanwhile, the relative bioavailability of specnuezhenide and oleanolic acid was greater than 100% with administration of the wine-steamed product, consistent with the Traditional Chinese Medicine theory of the wine-steamed product being more effective than the raw material. The results reveal the different pharmacokinetic parameters and relative bioavailability of each component of Ligustri Lucidi Fructus and its wine-steamed product, and also demonstrate the variation and correlation of various components in vivo and in vitro, providing an experimental basis for the selection of quality control indexes, mechanisms of processing and the metabolic rule in vivo of Ligustri Lucidi Fructus. These experiments were approved by the Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medicine Science.

Comparison of the Prognostic Value of Platelet-Related Indices in Biliary Tract Cancer Undergoing Surgical Resection / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Platelet-related indices, including mean platelet volume (MPV) and plateletocrit (PCT), have been reported as new prognostic factors of overall survival (OS) in many cancers, but not yet in biliary tract cancer (BTC). We intended to assess these indices in predicting OS in BTC patients with the aim to build a new prognostic model for patients with BTC after surgical resection. @*Materials and Methods@#Survival analysis and time receiver operating characteristic analysis were applied to screen the platelet indices. Univariate and multivariate Cox analyses were used to identify independent prognostic factors and develop a new prognostic model. Harrell’s C-statistics, calibration curves, and decisive curve analysis were used to assess the model. @*Results@#MPV and platelet distribution width (PDW)/PCT showed the best prognostic accuracy among the platelet indices. In multivariable analysis, factors predictive of poor OS were presence of nodal involvement, Non-radical surgery, poor tumor differentiation, carbohydrate antigen 19-9 > 100 U/mL, MPV > 8.1 fl, and PDW/PCT > 190. The new model was found to be superior to the TNM staging system and our new staging system showed higher discriminative power. @*Conclusion@#MPV and PDW/PCT have high prognostic value in BTC patients, and the novel staging system based on these two indices showed good discrimination and accuracy compared with the American Joint Committee on Cancer 7th TNM staging system.

Double Tract Reconstruction Reduces Reflux Esophagitis and Improves Quality of Life after Radical Proximal Gastrectomy for Patients with Upper Gastric or Esophagogastric Adenocarcinoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The aim of the present study was to compare the difference between double tract reconstruction and esophagogastrostomy. @*Materials and Methods@#Patients who underwent radical proximal gastrectomy with esophagogastrostomy or double tract reconstruction were included in this study. @*Results@#Sixty-four patients were included in this study and divided into two groups according to reconstruction method. The two groups were well balanced in perioperative safety and 3-year overall survival (OS). The rates of postoperative reflux esophagitis in the double tract reconstruction group and esophagogastrostomy group were 8.0% and 30.8%, respectively (p=0.032). Patients in the double tract reconstruction group had a better global health status (p < 0.001) and emotional functioning (p < 0.001), and complained less about nausea and vomiting (p < 0.001), pain (p=0.039), insomnia (p=0.003), and appetite loss (p < 0.001) based on the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire. Regarding the EORTC QLQ-STO22 questionnaire, patients in the double tract reconstruction group complained less about dysphagia (p=0.030), pain (p=0.008), reflux (p < 0.001), eating (p < 0.001), anxiety (p < 0.001), dry mouth (p=0.007), and taste (p=0.001). The multiple linear regression analysis showed that reconstruction method, postoperative complications, reflux esophagitis, and operation duration had a linear relationship with the global health status score. @*Conclusion@#Double tract reconstruction could better prevent reflux esophagitis and improve quality of life without scarifying perioperative safety or 3-year OS.

Qualitative and quantitative analysis on triterpenoids in Ligustri Lucidi Fructus / 中国中药杂志

Triterpenoids are one of the most active constituents in Ligustri Lucidi Fructus, but only oleanolic acid has been mostly studied. In recent years, a growing number of studies have shown that other triterpenes from Ligustri Lucidi Fructus also have various biological activities, so it is necessary to build up a detailed profile of the triterpenoids in Ligustri Lucidi Fructus. The chromatographic separation was performed on a C_(18) column(4.6 mm×250 mm, 5 μm) with mobile phase of methanol-acetonitrile-0.2% formic acid for gradient elution. The detection wavelength was set at 210 nm, with a flow rate of 0.5 mL·min~(-1), and the column temperature of 25 ℃. The HPLC fingerprint of triterpenoids in Ligustri Lucidi Fructus was built by testing 21 batches of samples from different sources. The structures of the total 15 common chromatographic peaks were elucidated with UHPLC-ESI-Orbitrap-MS/MS technique and six of them were identified as tormentic acid, pomolic acid, maslinic acid, botulin, oleanolic acid and ursolic acid by comparison to the reference substances. Under the same chromatographic condition, four main triterpenes(podocarboxylic acid, hawthorn acid, oleanolic acid and ursolic acid) were quantified and the results of system adaptability and methodology investigation all met the requirements of content determination. Meanwhile, with oleanolic acid(A) as the internal reference substance, quantitative analysis of multi-components by single marker(QAMS) method was used to analyze the above four components. The relative correction factor of oleanolic acid(B), hawthorn acid(C) and ursolic acid(D) to oleanolic acid was f_(B/A)=1.12, f_(C/A)=1.02 and f_(D/A)=0.88, respectively, and the relative retention values of these three to oleanolic acid was RRV_(B/A)=0.46, RRV_(C/A)=0.70 and RRV_(D/A)=1.03, respectively. The contents determined by two methods were similar. In conclusion, the method built in this paper is proved to be simple, reliable and specific for the simultaneous qualitative and quantitative analysis of the triterpenoids in Ligustri Lucidi Fructus, which can lay foundation for further assays of the triterpenoids in Ligustri Lucidi Fructus and the relative products.

Bevacizumab Combined with Icotinib Overcomes Osimertinib Resistance in a Patient of Non-Small Cell Lung Cancer / 中国医学科学杂志(英文版)

A 61-year-old Chinese woman was diagnosed as primary pulmonary adenocarcinoma of left superior lobe with epidermal growth factor receptor (EGFR) 19 del mutation positive. Treatment with icotinib was given, but her disease progressed after 6 months remission. CT-guide needle biopsy for the new lesion in inferior lobe of left lung demonstrated intrapulmonary metastasis, and EGFR gene panel by Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR) confirmed EGFR T790M mutation. Treatment with osimertinib was initiated. After 2 months remission, the disease progressed. Re-biopsy was performed for the tumor in the inferior lobe of left lung, and ARMS-PCR demonstrated no other gene mutation except EGFR 19 del. Icotinib was re-challenged, but disease progressed continuously. Bevacizumab was added, and partial response was achieved after 2-cycle of combination therapy. The non-small cell lung cancer (NSCLC) in this case maintained EGFR activating mutation and lost EGFR T790M mutation was a genetic change after osimertinib treatment. This case suggests the re-challenge of the first-generation EGFR-TKIs combined with bevacizumab may overcome the tumor resistance and prolong survival of NSCLC patient.

Qualitative and quantitative analysis on non-triterpenoids in Ligustri Lucidi Fructus / 中国中药杂志

In order to improve the quality control level of Ligustri Lucidi Fructus(LLF) and to explore the changes of chemical components after processing,the HPLC method for fingerprint and simultaneous determination of the major polar components in LLF were established. The octadecylsilane bonded silica gel was used as the stationary phase,with acetonitrile as the mobile phase A and0. 2% formic acid as the mobile phase B in a gradient elution procedure at a flow rate of 1. 0 m L·min-1. The detection wavelength was set at 280 nm and the column temperature was 25 ℃. There were 22 common peaks,20 of which were selected from the fingerprint of LLF and its wine-steamed product,respectively,and 14 chromatographic peaks were identified with reference substances. With the same chromatographic conditions,seven components were quantitatively analyzed and the results of system adaptability and methodology investigation all met the requirements of content determination. Compared with the crude LLF,the content of 5-hydroxymethyl furfural and salidroside significantly increased in wine-steamed LLF,while the contents of iridoid glycosides generally decreased. The method provided a basis for quality control of LLF and its processed products as well as the related preparations.

Persistently Upregulated Hippocampal mTOR Signals Mediated by Fecal SCFAs Impair Memory in Male Pups with SMM Exposure in Utero / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the molecular mechanisms of the adverse effects of exposure to sulfamonomethoxin (SMM) in pregnancy on the neurobehavioral development of male offspring.@*METHODS@#Pregnant mice were randomly divided into four groups: control- (normal saline), low- [10 mg/(kg•day)], middle- [50 mg/(kg•day)], and high-dose [200 mg/(kg•day)] groups, which received SMM by gavage daily during gestational days 1-18. We measured the levels of short-chain fatty acids (SCFAs) in feces from dams and male pups. Furthermore, we analyzed the mRNA and protein levels of genes involved in the mammalian target of rapamycin (mTOR) pathway in the hippocampus of male pups by RT-PCR or Western blotting.@*RESULTS@#Fecal SCFA concentrations were significantly decreased in dams. Moreover, the production of individual fecal SCFAs was unbalanced, with a tendency for an increased level of total fecal SCFAs in male pups on postnatal day (PND) 22 and 56. Furthermore, the phosphatidylinositol 3-kinase (PI3k)/protein kinase B (AKT)/mTOR or mTOR/ribosomal protein S6 kinase 1 (S6K1)/4EBP1 signaling pathway was continuously upregulated until PND 56 in male offspring. In addition, the expression of Sepiapterin Reductase (SPR), a potential target of mTOR, was inhibited.@*CONCLUSION@#In utero exposure to SMM, persistent upregulation of the hippocampal mTOR pathway related to dysfunction of the gut (SCFA)-brain axis may contribute to cognitive deficits in male offspring.

Clinical application of percutaneous transforaminal endoscope-assisted lumbar interbody fusion / 中国骨伤

OBJECTIVE@#To conclude of the technical notes of percutaneous transforaminal endoscope-assisted lumbar interbody fusion (PT-Endo-LIF), and to investigate its safety and efficacy for treatment of degenerative lumbar disease.@*METHODS@#Twenty-four patients were treated by PT-Endo-LIF combined with posterior percutaneous pedicle screws fixation from October 2017 to April 2018. There were 16 males and 8 females, ranging in age from 39 to 72 years old, with a mean of (59.6±9.5) years old. There were 15 cases diagnosed with lumbar intervertebral disc herniation combined with degenerative disc, the other 9 cases were diagnosed as low level lumbar spondylolistheses w/o segmental instability. Single segmental fusion was performed for 22 cases(one for L₂,₃, 3 for L₃,₄ and 18 for L₄,₅) and 2 segmental fusion was performed for the other 2 cases (both for L₃,₄ and L₄,₅). PT-Endo-LIF was performed under local anesthesia with conscious sedation, followed by decompression through endoscopic technics. After that, end-plate preparation and autogenous bone and expandable cage implantation were performed. Finally, percutaneous screws and rod instrumentation were used. The visual analogue scale (VAS) and Oswestry Disability Index (ODI) were used to evaluate the clinical efficacy. The operation time, intraoperative bleeding volume, intraoperative and postoperative complications were recorded. All patients underwent X-ray, CT plain scan, three-dimensional reconstruction and MRI examination to evaluate the stability of the implants and fusion rate before 3 days and 1, 3, 6, 12 and 18 months after operation.@*RESULTS@#All patients were followed up, and the duration ranged from 12 to 18 months. The operation time of single-segment fusion was (192.3±22.7) min, and that of double-segment fusion was (272.5±24.7) min. The estimated intraoperative bleeding volume was less than 50 ml per segment, and no blood transfusion was performed in all patients. The VAS improved from preoperative 7.4±1.1 to postoperative 2.3±0.8 (=-19.65, <0.000 5). The ODI improved from preoperative (41.2±3.3)% to the final follow-up (12.3±2.5)%(=-35.76, <0.000 5). Postoperative complications occurred in 4 cases, and contralateral radicular symptoms occurred in 2 cases. After contralateral foraminoscopic decompression, the symptoms were completely alleviated. One case had neurological symptoms related to percutaneous screw placement, and the symptoms were alleviated after removal of the lateral screw rod internal fixation. The other cases had surgical incision infection and improved after debridement and suture. At the latest follow-up, no displacement or loosening of the fusion cage and screw rod system occurred in all patients, and 14 cases showed signs of fusion.@*CONCLUSIONS@#PT-Endo-LIF is a minimal invasive, safe and efficient surgical procedure for treatment of degenerative lumbar disease. Nevertheless, the long-term results still need to be confirmed by a multi-center and lagre sample follow-up study.

Progress on surgical treatment of isthmic spondylolisthesis / 中国骨伤

Isthmic spondylolisthesis is a common degenerative disease of the spine and seriously affects people's quality of life. At present, surgical indications for lumbar spondylolisthesis have basically reached consensus. The surgical plan for the disease is mainly isthmus repair, decompression of spinal canal, reduction of spondylolisthesis, and spinal fusion. The principle of treatment is mainly to relieve nerve compression and restore spinal stability, but for each the specific method and degree of implementation of the link still remains controversial. Open surgery can complete decompression, reduction and fusion of severe spondylolisthesis, and rebuild the stability of the spine. However, the surgical trauma is too large. Minimally invasive surgery can reduce the damage of paravertebral soft tissue, reduce intraoperative blood loss, shorten the time of hospitalization and rehabilitation, and reduce the incidence of intraoperative and postoperative complications. Therefore, in recent years, more and more clinicians praise it, but the treatment of severe spondylolisthesis lumbar spondylolisthesis is not effective. This article reviews recent advances in surgical treatment of lumbar spondylolisthesis.

The expression level of hsa_circ_0001649 incolorectal cancer and its clinical value / 西安交通大学学报(医学版)

Objective: To explore the expression level of hsa_circ_000164 9 in colorectal cancer (CRC). Methods: In this experiment, the expression level of hsa_circ_0001649 in CRC tissue was tested by using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCRs). Results: The expression level of hsa_circ_0001649 was obviously down-regulated in CRC tissue, compared with paired paracancerous histological normal tissues (PCHNTs) (P<0.010). Hsa_circ_0001649 was obviously up-regulated in the patients' peripheral blood after operation. The area under the receiver operating characteristic (ROC) curve was 0.828. We also found a significant connection between the expression level of hsa_circ_0001649 and pathological differentiation of CRC (P=0.039). Conclusion: hsa_circ_0001649 was obviously down-regulated in CRC; therefore, it may be used as a new biomarker in the diagnosis of CRC.

Study on correlation between adropin protein and homocysteine level in patients with coronary artery disease / 国际检验医学杂志

Objective To investigate the correlation between serum adropin protein and homocysteine (Hcy) level in the patients with coronary artery disease (CAD) ,and to study their relationship with CAD se-verity .Methods One hundred and seventy cases of CAD in this hospital from August 2015 to October 2016 were selected as the research subjects .Peripheral blood was collected for measuring serum adropin protein , Hcy and other conventional biochemical indicators ,and the coronary artery lesion was detected by coronary an-giography ,the severity of coronary artery lesion was assessed by SYNTAX score .Results In 170 cases of CAD ,mean serum Hcy level was (15 .92 ± 8 .31)μmol/L ,the adropin protein level in the hyperhomocysteine-mia group was lower than that in the non-hyperhomocysteinemia group ,the difference was statistically signifi-cant(P<0 .05) .Mean SYNTAX score in all cases was (21 .51 ± 11 .20) points ,and serum adropin protein was negatively correlated with Hcy level (r= -0 .169 ,P= 0 .028) ,serum Hcy level had no obvious correlation with SYNTAX score (r= 0 .124 ,P=0 .108) ,the adropin protein level was negatively correlated with SYN-TAX score (r= -0 .181 ,P=0 .018) .Generalized structural equation model showed that with the decrease of adropin protein level ,the SYNTAX score was increased (P=0 .019) ,compared with the patients without com-plicating hyperhomocysteinemia ,the SYNTAX score in the patients with hyperhomocysteinemia was much higher(P=0 .005) .Conclusion The lower the adropin protein level ,the higher the Hcy level and the severe the coronary artery lesion .