Current Status and Challenges of Biological Sample Management in Clinical Trials / 中国医学伦理学

With the rapid development of clinical trials, the relevant medical research and molecular detection based on biological samples are closely related to the progress of clinical trials, making the role of biological samples in clinical trials increasingly obvious. The standardized supervision mode of biological samples is an important prerequisite for carrying out high-quality clinical trials. Although the laws and regulations related to clinical trials are becoming more and more perfect, there are still a large number of adverse events related to biological samples, which seriously affects the progress and results of clinical trials, and is one of the important challenges currently facing. Therefore, it is urgent to enhance the supervision of biological samples and improve the management methods of biological samples in clinical trials at this stage. Through in-depth discussion of the current status of biological sample management in clinical trials at home and abroad, this paper analyzed the issues existed during the supervision of biological samples, and supplemented the biological sample management methods by further combing the existing relevant laws and regulations and the Guidelines for the Ethical Management of Biological Samples in Clinical Trials, with a view to providing suggestions and ideas for optimizing the management mode of biological samples in clinical trials.

Discussion on the essential thought of Ma's warm moxibustion technique for "unblocking fu-organs" / 中国针灸

"Unblocking fu organs" is one of the essential principles of Ma's warm moxibustion technique, characterized as "dredging" and "harmonizing" for either deficiency or excess condition. Under the guidance of this therapeutic thought, the acupoints for moxibustion are mainly selected from the middle and lower parts of the body. Regarding the therapeutic approach, the acupoint prescription for moxibustion should be formed in line with warming and promoting circulation of fu organs; the moxibustion degree should be specially considered, in which, the mild moxibustion is recommended to induce promoting action; and the systematic moxibustion technique should be the root for dredging fu organs and regulating zang organs. Ma's mild moxibustion technique stresses on removing the obstruction of fu organs and emphasizes promoting the qi activity of sanjiao (triple energizer) and regulating the balance of five zang organs.

Periodontitis may induce gut microbiota dysbiosis via salivary microbiota / 国际口腔科学杂志·英文版

The aim of this study was to identify whether periodontitis induces gut microbiota dysbiosis via invasion by salivary microbes. First, faecal and salivary samples were collected from periodontally healthy participants (PH group, n = 16) and patients with severe periodontitis (SP group, n = 21) and analysed by 16S ribosomal RNA sequencing. Significant differences were observed in both the faecal and salivary microbiota between the PH and SP groups. Notably, more saliva-sourced microbes were observed in the faecal samples of the SP group. Then, the remaining salivary microbes were transplanted into C57BL6/J mice (the C-PH group and the C-SP group), and it was found that the composition of the gut microbiota of the C-SP group was significantly different from that of the C-PH group, with Porphyromonadaceae and Fusobacterium being significantly enriched in the C-SP group. In the colon, the C-SP group showed significantly reduced crypt depth and zonula occludens-1 expression. The mRNA expression levels of pro-inflammatory cytokines, chemokines and tight junction proteins were significantly higher in the C-SP group. To further investigate whether salivary bacteria could persist in the intestine, the salivary microbiota was stained with carboxyfluorescein diacetate succinimidyl ester and transplanted into mice. We found that salivary microbes from both the PH group and the SP group could persist in the gut for at least 24 h. Thus, our data demonstrate that periodontitis may induce gut microbiota dysbiosis through the influx of salivary microbes.

Effect of Dingkundan in Adjuvant Treatment of Patients with Radiotherapy and Chemotherapy After Endometrial Carcinoma Operation / 中国实验方剂学杂志

Objective:To observe the effect of Dingkundan in adjuvant treatment of clinical symptoms， quality of life， immune function and prognosis of patients with radiotherapy and chemotherapy after endometrial carcinoma （EC） operation. Method:Patients were divided into control group （82 cases） and observation group （86 cases） according to random number table. A total of 75 patients in control group completed the study （4 patients fell off or lose visit， and 3 patients were eliminated）， while 77 patients in observation group completed the study （5 patients fell off or lose visit， and 4 patients were deleted）. After operation， patients got brachytherapy， external pelvic irradiation and chemotherapy. Patients in control group got Bazhenwan， 1 pill/time， 2 times/day， and those in observation group got Dingkundan， 7 g/time， 2 times/day. The course of treatment lasted for 4 months， and long-time follow-up data was recorded. Before treatment， and at the second and fourth month after treatment， deficiency of Qi and blood was scored. Toxic reactions after radiotherapy and chemotherapy were recorded， and incidence rate of acute and advanced radiation injury of bladder and rectum and toxicity of chemotherapeutic drugs at grade 3 or above grade 3 level were compared. And levels of T lymphocyte subsets （CD3⁺， CD4⁺， CD8⁺ and CD4⁺/CD8⁺） were detected， European collaborative quality of life Cancer Core Scale （EORTC QLQ-C30） was evaluated， and expressions of pce125 （CA125）， epididymis protein 4 （HE4）， Dickkopf-related protein-1 （DKK1）， vascular endothelial growth factor （VEGF）， matrix metalloproteinase-9 （MMP-9） and transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁） were tested before and after treatment. The follow-up was made for every three months， and the progression （recurrence/metastasis） of patients was recorded. Result:Scores of deficiency of Qi and blood in observation group were lower than those in control group at the second and fourth week after treatment （<italic>P</italic><0.01）. Incidence rates of acute and advanced radiation injury of bladder and rectum and toxicity of chemotherapeutic drugs at grade 3 or above grade 3 level and incidence rates of bone marrow suppression， gastrointestinal toxicity， neurotoxicity were lower than those in control group （<italic>P</italic><0.05）. Five functional dimensions and overall quality of life score based on EORTC and QLQ-C30 in observation group were higher than those in control group （<italic>P</italic><0.01）， and scores of three symptom dimensions were lower than those in control group （<italic>P</italic><0.01）. Levels of CD3⁺， CD4⁺ and CD4⁺/CD8⁺ were higher than those in the control group （<italic>P</italic><0.01）， and CD8⁺ was lower than those in the control group （<italic>P</italic><0.01）. Levels of CA125， HE4， DKK1， VEGF， MMP-9 and TGF-<italic>β</italic>₁ were lower than those in the control group （<italic>P</italic><0.01）. The disease progression rate in observation group was 18.18% （14/77）， which was lower than 33.33% （25/75） in control group （<italic>χ</italic>²=4.572， <italic>P</italic><0.05）. Conclusion:In adjuvant treatment of patients with radiotherapy and chemotherapy after EC operation， Dingkundan can reduce the symptoms of Qi and blood deficiency syndrome and side effects caused by radiotherapy and chemotherapy， improve the quality of life and immune function， inhibit the expression of tumor markers and tumor growth factor， delay the progression of tumor and improve the prognosis.

Baseline left ventricular ejection fraction associated with symptom improvements in both children and adolescents with postural tachycardia syndrome under metoprolol therapy / 中华医学杂志(英文版)

BACKGROUND@#Postural tachycardia syndrome (POTS) is a common childhood disease that seriously affects the patient's physical and mental health. This study aimed to investigate whether pre-treatment baseline left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) values were associated with symptom improvement after metoprolol therapy for children and adolescents with POTS.@*METHODS@#This retrospective study evaluated 51 children and adolescents with POTS who received metoprolol therapy at the Peking University First Hospital between November 2010 and July 2019. All patients had completed a standing test or basic head-up tilt test and cardiac echocardiography before treatment. Treatment response was evaluated 3 months after starting metoprolol therapy. The pre-treatment baseline LVEF and LVFS values were evaluated for correlations with decreases in the symptom score after treatment (ΔSS). Multivariable analysis was performed using factors with a P value of  0.050). However, responders had significantly higher baseline LVEF (71.09% ± 4.44% vs. 67.17% ± 4.88%, t = -2.789, P = 0.008) and LVFS values (40.00 [38.00, 42.00]% vs. 36.79% ± 4.11%, Z = -2.542, P = 0.010) than the non-responders. The baseline LVEF and LVFS were positively correlated with ΔSS (r = 0.378, P = 0.006; r = 0.363, P = 0.009), respectively. Logistic regression analysis revealed that LVEF was independently associated with the response to metoprolol therapy in children and adolescents with POTS (odds ratio: 1.201, 95% confidence interval: 1.039-1.387, P = 0.013).@*CONCLUSIONS@#Pre-treatment baseline LVEF was associated with symptom improvement after metoprolol treatment for children and adolescents with POTS.

Body mass index is a promising predictor of response to oral rehydration saline in children with vasovagal syncope / 中华医学杂志(英文版)

BACKGROUND@#Vasovagal syncope (VVS) greatly impairs quality of life. The therapeutic efficacy of oral rehydration saline (ORS) for unselected VVS patients is not satisfactory due to the diverse mechanisms of the disease. Body mass index (BMI) was demonstrated to reflect blood volume to a certain extent. Therefore, the present study explored the capability of BMI to predict the therapeutic response of children with VVS to ORS treatment.@*METHODS@#Seventy-four children with VVS who visited the Syncope Unit of Pediatrics at Peking University First Hospital from November 2010 to June 2019 receiving ORS treatment were enrolled for this retrospective case-control study. A comparison of demographic, clinical, and hemodynamic characteristics was performed between responders and non-responders. The correlation between baseline BMI and response time was analyzed. To determine the value of baseline BMI in predicting the therapeutic efficacy of ORS in children with VVS, a receiver operating characteristic curve analysis was performed.@*RESULTS@#Fifty-two children were identified as responders, and the remaining 22 children were identified as non-responders. The baseline BMI of the responders was much lower than that of the non-responders (16.4 [15.5, 17.8] kg/m2vs. 20.7 ±e6 kg/m2, P < 0.001), and baseline BMI was positively correlated with response time in the head-up tilt test after adjusting for sex (r = 0.256, 95% confidence interval [CI]: 0.067-0.439, P = 0.029). The area under the receiver operating characteristic curve of baseline BMI was 0.818 (95% CI: 0.704-0.932, P < 0.001), and an optimal cut-off value of 18.9 kg/m2 yielded a sensitivity of 83% and a specificity of 73% to predict the efficacy of ORS in VVS.@*CONCLUSION@#Prior to treatment, baseline BMI is a promising predictor of response to ORS in children with VVS.

Gut microbiota analysis and its significance in vasovagal syncope in children / 中华医学杂志(英文版)

BACKGROUND@#Vasovagal syncope (VVS) is common in children and greatly affect both physical and mental health. But the mechanisms have not been completely explained. This study was designed to analyze the gut microbiota in children with VVS and explore its clinical significance.@*METHODS@#Fecal samples from 20 VVS children and 20 matched controls were collected, and the microbiota were analyzed by 16S rRNA gene sequencing. The diversity and microbiota compositions of the VVS cases and controls were compared with the independent sample t test or Mann-Whitney U test. The correlation between the predominant bacteria and clinical symptoms was analyzed using Pearson or Spearman correlation test.@*RESULTS@#No significant differences in diversity were evident between VVS and controls (P > 0.05). At the family level, the relative abundance of Ruminococcaceae was significantly higher in VVS children than in controls (median [Q1, Q3]: 22.10% [16.89%, 27.36%] vs. 13.92% [10.31%, 20.18%], Z = -2.40, P  4, P < 0.05). The relative abundance of Ruminococcaceae in VVS patients was positively correlated with the frequency of syncope (r = 0.616, P < 0.01). In terms of its correlation with hemodynamics, we showed that relative abundance of Ruminococcaceae was negatively correlated with the systolic and diastolic pressure reduction at the positive response in head-up tilt test (HUTT; r = -0.489 and -0.448, all P < 0.05), but was positively correlated with the mean pressure drop and decline rate (r = 0.489 and 0.467, all P < 0.05) as well as diastolic pressure drop and decline rate at the HUTT positive response (r = 0.579 and 0.589, all P < 0.01) in VVS patients.@*CONCLUSION@#Ruminococcaceae was the predominant gut bacteria and was associated with the clinical symptoms and hemodynamics of VVS, suggesting that gut microbiota might be involved in the development of VVS.

Drug resistance and molecular characteration of hemagglutinin and neuraminidase for influenza A H3N2 viruses / 医学研究生学报

Objective　To analyze the variations and drug resistance of influenza A (H3N2) viruses in Jiangsu Province in 2017, and provide evidence for prevention and control strategies on influenza.　Methods　Reverse transcription polymerase chain reaction (RT-PCR) was used for the sequencing of H3N2 subtype influenza strains. The influenza reference sequences were obtained from the global shared influenza site GISAID. The sequence alignment and phylogenetic analysis were performed using MAGE7.0 software. Viral resistance was analyzed by a neuraminidase inhibition assay.　Results　The H3N2 subtype influenza isolates and vaccine strains belonged to the 3C.2a branch of the H3 subtype. Some of the strains showed amino acid mutations on the immune-related sites named N121K, T135K and N171K. The isolates were sensitive to the flu drugs oseltamivir and zanamivir.　Conclusion　The H3N2 epidemic strains in Jiangsu have genetic recombination within subtypes and are still sensitive to neuraminidase inhibitors. As the H3N2 influenza virus mutations continue, a close monitoring of the viral genetic evolution and the drug resistant genes should be guaranteed.

Hemodynamic changes in standing-up test of children and adolescents with postural tachycardia syndrome / 北京大学学报(医学版)

OBJECTIVE@#To explore the hemodynamic changes in standing-up test of children and adolescents with postural tachycardia syndrome (POTS) and to compare hemodynamic parameters of POTS patients with decreased cardiac index (CI) and those with not-decreased CI.@*METHODS@#A retrospective study was conducted to show the trends of CI, total peripheral vascular resistance index (TPVRI), heart rate and blood pressure in standing-up test of 26 POTS patients and 12 healthy controls, and to compare them between the two groups. The POTS patients were divided into two groups based on CI decreasing or not in standing-up test, namely decreased CI group (14 cases) and not-decreased CI group (12 cases). The trends of the above mentioned hemodynamic parameters in standing-up test were observed and compared between decreased CI group and not-decreased CI group.@*RESULTS@#In standing-up test for all the POTS patients, CI (F=6.936, P=0.001) and systolic blood pressure (F=6.049, P<0.001) both decreased significantly, and heart rate increased obviously (F=113.926, P<0.001). However, TPVRI (F=2.031, P=0.138) and diastolic blood pressure (F=2.018, P=0.113) had no significant changes. For healthy controls, CI (F=3.646, P=0.016), heart rate (F=43.970, P<0.001), systolic blood pressure (F=4.043, P=0.020) and diastolic blood pressure (F=8.627, P<0.001) all increased significantly in standing-up test. TPVRI (F=1.688, P=0.190) did not change obviously. The changing trends of CI (F=6.221, P=0.001), heart rate (F=6.203, P<0.001) and systolic blood pressure (F=7.946, P<0.001) over time were significantly different between the patients and healthy controls, however, no difference was found in TPVRI and diastolic blood pressure (P > 0.05). Among the POTS patients, CI was significantly different between decreased CI group and not-decreased CI group (F=14.723, P<0.001). Systolic blood pressure of the former decreased obviously (F=8.010, P<0.001), but it did not change obviously in the latter (F=0.612, P=0.639). Furthermore, none of the changes of TPVRI, heart rate and diastolic blood pressure in standing-up test were significantly different between the two groups (P > 0.05). Age was an independent factor for decreased CI patients (P=0.013, OR=2.233; 95% CI, 1.183 to 4.216).@*CONCLUSION@#POTS patients experience vital hemodynamic changes in standing-up test, part of them suffering from decreased CI, but others from not-decreased CI. Age is an independent factor for patients suffering from decreased CI.

Functional Magnetic Resonance Imaging in the Diagnosis of Locally Recurrent Prostate Cancer: Are All Pulse Sequences Helpful?

OBJECTIVE: To perform a meta-analysis to quantitatively assess functional magnetic resonance imaging (MRI) in the diagnosis of locally recurrent prostate cancer. MATERIALS AND METHODS: A comprehensive search of the PubMed, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews was conducted from January 1, 1995 to December 31, 2016. Diagnostic accuracy was quantitatively pooled for all studies by using hierarchical logistic regression modeling, including bivariate modeling and hierarchical summary receiver operating characteristic (HSROC) curves (AUCs). The Z test was used to determine whether adding functional MRI to T2-weighted imaging (T2WI) results in significantly increased diagnostic sensitivity and specificity. RESULTS: Meta-analysis of 13 studies involving 826 patients who underwent radical prostatectomy showed a pooled sensitivity and specificity of 91%, and the AUC was 0.96. Meta-analysis of 7 studies involving 329 patients who underwent radiotherapy showed a pooled sensitivity of 80% and specificity of 81%, and the AUC was 0.88. Meta-analysis of 11 studies reporting 1669 sextant biopsies from patients who underwent radiotherapy showed a pooled sensitivity of 54% and specificity of 91%, and the AUC was 0.85. Sensitivity after radiotherapy was significantly higher when diffusion-weighted MRI data were combined with T2WI than when only T2WI results were used. This was true when meta-analysis was performed on a per-patient basis (p = 0.027) or per sextant biopsy (p = 0.046). A similar result was found when ¹H-magnetic resonance spectroscopy (¹H-MRS) data were combined with T2WI and sextant biopsy was the unit of analysis (p = 0.036). CONCLUSION: Functional MRI data may not strengthen the ability of T2WI to detect locally recurrent prostate cancer in patients who have undergone radical prostatectomy. By contrast, diffusion-weight MRI and ¹H-MRS data may improve the sensitivity of T2WI for patients who have undergone radiotherapy.

Clinical Analysis of Treating EBV Infection Accompanied with GVHD after Allon-HSCT by EBV-Specific Cytotoxic T Lymphocytes / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficiency and safety of treating Epstein-Barr virus (EBV) infection of acute graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) by EBV specific cytotoxic T lymphocytes (EBV-CTL).</p><p><b>METHODS</b>The Clinical characteristics, therapeutic efficacy and safety of 12 patients with EBV infection treated by EBV-CTL infusion after allo-HSCT in Department of Hemahlogy of Aero Space Center Hospital between Jan 2015 and May 2017 were analyzed retrospectioely.</p><p><b>RESULTS</b>Our of 12 cases received EBV-CTL infusion after transplantation, 9 did not received Rituximab therapy due to the active infection, 4 cases including 3 received Ritaximab progressed into posttransplantation lymphoroliferetive disease (PTLD). The median time of EBV infection was 47 (22-71) days, median time of antivirus therapy before tramplantation was 10 (8-33) days, median time of first CTL infusion was 59(34-86) days after transplatation. The 43 cases-time CTL infusion was performed smoothly, no related harmful evnts occoured, no progression of GVHD was observed. After the first course of infusion, complete remission (CR), Partial remssion (PR) and no remssion (NR) were obtained in 9, 1 and 2 patients respectively, the relapse was observed in 4 patients who then received the socond course of infusion and all reached CR, the patient in PR did not reathed CR finally and died of GVGD at 5 months after transpplantation . Only 1 out of 2 cases of NR obtained CR, another 1 still was in NR, and died of transplantation related infection at 5 months after transplantation. 4 cases of PTLD were all cared.</p><p><b>CONCLUSION</b>Preliminary results of this study suggest that EBV-CTL infusion is safe for the EBV infection combined with acute GVHD after all-HSCT. However, a further larger scale clinical studies are needed to prove the efficiency.</p>

Inhibitory Effects of Sulfur Dioxide on Rat Myocardial Fibroblast Proliferation and Migration / 中华医学杂志(英文版)

<p><b>Background</b>Myocardial fibrosis is an important pathological change in many heart diseases, but its pathogenesis is very complex and has not yet been fully elucidated. The study was designed to examine whether endogenous sulfur dioxide (SO) is a novel myocardial fibroblast proliferation and migration inhibitor.</p><p><b>Methods</b>Primary rat myocardial fibroblasts were isolated and transfected with aspartate aminotransferase (AAT1 and AAT2) knockdown lentivirus or empty lentivirus. SO content in the supernatant was determined with high-performance liquid chromatography, and the expressions of AAT1, AAT2, proliferating cell nuclear antigen (PCNA), phosphorylated extracellular signal-regulated protein kinase (p-ERK), and total ERK (T-ERK) in the cells were detected. Cell migration was detected by wound healing test. Independent sample t-test (for two groups) and one-way analysis of variance (three or more groups) were used to analyze the results.</p><p><b>Results</b>Both AAT1 and AAT2 knockdown significantly reduced SOlevels (F = 31.46, P < 0.01) and AAT1/2 protein expression (AAT1, t = 12.67, P < 0.01; AAT2, t = 9.61, P < 0.01), but increased PCNA expression and Cell Counting Kit-8 (CCK-8) activity as well as the migration in rat primary myocardial fibroblasts (P < 0.01). Supplementation of SOrather than pyruvate significantly inhibited the increase in proliferation and migration caused by AAT knockdown (P < 0.01). Mechanistically, the ratio of p-ERK to T-ERK was significantly increased in the AAT1/2 knockdown groups compared with that in the empty lentivirus group (AAT1, t = -7.36, P < 0.01; AAT2, t = -10.97, P < 0.01). Whereas PD98059, an inhibitor of ERK activation, successfully blocked AAT knockdown-induced PCNA upregulation (F = 74.01, P > 0.05), CCK-8 activation (F = 50.14, P > 0.05), and migration augmentation in myocardial fibroblasts (24 h, F = 37.08, P > 0.05; 48 h, F = 58.60, P > 0.05).</p><p><b>Conclusion</b>Endogenous SOmight be a novel myocardial fibroblast proliferation and migration inhibitor via inhibiting the ERK signaling pathway.</p>

Hydrogen Sulfide Regulating Myocardial Structure and Function by Targeting Cardiomyocyte Autophagy / 中华医学杂志(英文版)

<p><b>Objective</b>Hydrogen sulfide (HS), a gaseous signal molecule, plays a crucial role in many pathophysiologic processes in the cardiovascular system. Autophagy has been shown to participate in the occurrence of many cardiac diseases. Increasing evidences indicated that HS regulates myocardial structure and function in association with the altered autophagy and plays a "switcher" role in the autophagy of myocardial diseases. The aim of this review was to summarize these insights and provide the experimental evidence that HS targets cardiomyocyte autophagy to regulate cardiovascular function.</p><p><b>Data Sources</b>This review was based on data in articles published in the PubMed databases up to October 30, 2017, with the following keywords: "hydrogen sulfide," "autophagy," and "cardiovascular diseases."</p><p><b>Study Selection</b>Original articles and critical reviews on HS and autophagy were selected for this review.</p><p><b>Results</b>When autophagy plays an adaptive role in the pathogenesis of diseases, HS restores autophagy; otherwise, when autophagy plays a detrimental role, HS downregulates autophagy to exert a cardioprotective function. For example, HS has beneficial effects by regulating autophagy in myocardial ischemia/reperfusion and plays a protective role by inhibiting autophagy during the operation of cardioplegia and cardiopulmonary bypass. HS postpones cardiac aging associated with the upregulation of autophagy but improves the left ventricular function of smoking rats by lowering autophagy.</p><p><b>Conclusions</b>HS exerts cardiovascular protection by regulating autophagy. Cardiovascular autophagy would likely become a potential target of HS therapy for cardiovascular diseases.</p>

Expression of Spns2 in gastric cancer tissue and its effect on the proliferation and migration of gastric cancer cells / 医学研究生学报

Objective Few studies are reported on the correlation of Spinster homolog2(Spns2) with cancer.This study aims to investigate the expression of Spns2 in gastric cancer and the adjacent tissue and explore its effects on the proliferation, clone formation and migration of human gastric cancer cell line SGC-7901.Methods Samples of gastric cancer and the adjacent tissue were collected from 20 patients (12 males and 8 females) after surgery between February 2016 and August 2016. The expression of Spns2 in the gastric cancer and adjacent tissues was determined by immunohistochemistry. Eukaryotic expression vector pEX-1 (pGCMV/MCS/EGFP/Neo)-Spns2 and siRNA were constructed and transfected into the human gastric cancer cell line SGC-7901. The cells were divided into a pEX-1- Spns2 (siRNA-Spns2) group and a negative control pEX-1 (siRNA-NC) group. The mRNA and protein expressions of Spns2 were detected by RT-PCR and Western blot, respectively. And the effects of Spns2 on the migration, clone formation and proliferation of the SGC-7901 cells after Spns2 over-expressed and down-regulated were evaluated by cell counting kit-8 (CCK-8) assay, clone formation assay, transwell experiment and wound healing scratch assay.Results The expression of Spns2 was significantly lower in the gastric cancer than in the adjacent tissue (0.39±0.04 vs 0.45±0.02, P<0.05). After transfection, both Spns2 mRNA and protein levels were remarkably higher in the pEX-1-Spns2 (21.96±2.08 and 10.71±2.78) than in the pEX-1 group (0.88±0.12 and 0.83±0.16) (P<0.05), but markedly lower in the siRNA-Spns2 (0.35±0.07 and 0.53±0.07) than in the siRNA-NC group (0.91±0.09 and 0.92±0.08) (P<0.05). At 48, 72 and 96 hours, the proliferation of the SGC-7901 cells was significantly decreased in the pEX-1-Spns2 group as compared with the pEX-1 group (P<0.05) but increased in the siRNA-Spns2 group in comparison with the siRNA-NC group (P<0.05); the clone formation rate was reduced in the pEX-1-Spns2 group as compared with the pEX-1 group (\[33.30±3.81\]％ vs \[48.00±4.60\]％, P<0.05) but elevated in the siRNA-Spns2 group in comparison with the siRNA-NC group (\[48.38±4.22\]％ vs \[26.25±4.88\]％, P<0.05).Conclusion Spns2 is lowly expressed in gastric cancer, and its over-expression in SGC-7901 cells can reduce its proliferation, clone formation and migration. Spns2 may play a role in inhibiting the development and progression of gastric cancer.

Influencing factors of postoperative complications of longitudinal fissure meningioma / 局解手术学杂志

Objective To evaluate the risk of microsurgery and reduce the incidence of postoperative complications in patients with lon-gitudinal fissure meningioma. Methods The clinical data of 106 patients with longitudinal fissure meningioma after microsurgery in the neu-rosurgery department of Xuzhou medical university from January 2011 to December 2017 were retrospectively analyzed.Longitudinal fissure meningioma were defined as the meningioma whose base were attached to the brain’s sickle sinus,sagittal sinus and the brain’s sickle sagit-tal sinus.Patients were divided into two groups according to whether there were postoperative complications.The gender,age,chief complaint symptoms,tumor base,tumor location,tumor size,tumor shape,MR enhancement,MR peritoneal edema, peritoneal adhesion of central sulcus vein and drainage vein,tumor invasiveness,tumor boundary,previous history of circulatory system were compared.Univariate analysis was per-formed on these factors to screen out the influencing factors of patients with postoperative complications.Binary logistic regression analysis was performed on the factors with statistical significance.Results Central sulcus vein and drainage vein adhesion were independent protective factors for postoperative complications.The risk of postoperative complications in patients without adhesion at peri-tumor stage was only 0.209 times of that in patients with adhesion.Conclusion For patients with longitudinal fissure meningioma,preoperative risk of postoperative com-plications can be assessed objectively according to the condition of central sulcus vein and drainage vein adhesion around the tumor.In the treatment of patients with obvious peritumoral vascular adhesion,the central sulcus vein and drainage vessels should be carefully protected to significantly reduce the incidence of postoperative complications.

Effect of down-regulation of X-box binding protein 1 gene expression on viability and apoptosis of glioma cells / 中国病理生理杂志

AIM:To investigate the effect of down-regulation of X-box binding protein 1(XBP1)expression on the viability and apoptosis of glioma cells.METHODS:The mRNA expression of XBP1 in the glioma tissues was de-tected by qPCR.Small interfering RNA(siRNA)interfering with XBP1 expression(XBP1-siRNA)was transfected into human brain glioma U251 cells.At the same time,control group(the cells without special treatment)and negative control (NC-siRNA)group(transfected with siRNA without any interference)were set up.The mRNA expression of XBP1 in the 3 groups 48 h after transfection was detected by qPCR.The protein levels of XBP1, proliferating cell nuclear antigen (PCNA),B-cell lymphoma/leukemia-2(Bcl-2),Bcl-2-associated X protein(Bax),cyclin D1(cyclin D1), phosphati-dylinositol 3-kinase(PI3K)and phosphorylated Akt(p-Akt)were determined by Western blot.The cell viability was measured by CCK-8 assay.The cell cycle distribution and apoptosis were analyzed by flow cytometry.RESULTS:The ex-pression level of XBP1 in the glioma tissues was significantly higher than that in the tumor adjacent tissues(P<0.05). The XBP1 expression at mRNA and protein levels was significantly decreased in the cells transfected with XBP1-siRNA(P<0.05).No statistically significant difference of the cell viability, cell cycle, apoptotic rate and the protein levels of PCNA,Bcl-2,Bax,cyclin D1,PI3K and p-Akt between NC-siRNA group and control group was observed.Compared with control group,the cell viability, S-phase cells and the protein levels of PCNA, Bcl-2, cyclin D1, PI3K, and p-Akt in XBP1-siRNA group were decreased significantly, and the apoptotic rate, G0/G1-phase cells and Bax protein expression were significantly increased(P<0.05).CONCLUSION:Down-regulation of XBP1 gene expression in brain glioma cells reduces the viability of cancer cells,blocks the cells in G1phase and promote apoptosis.The mechanism is related to the inhibition of PI3K/Akt signaling pathway.

The clinical significance of the expression of XB130 in gastric cancer tissues / 新乡医学院学报

Objective To investigate the relationship between the expression of XB130 and the histodifferentiation,lymph node metastasis and survival time of patients with gastric cancer.Methods Seventy-two specimens of gastric cancer tissues and seventy-two specimens of paracancerous tissues were collected from June 2011 to June 2012 in Henan Province People's Hospital.The expression of XB130 protein in gastric cancer and paracancerous tissues was detected by immunohistochemistry.The expression of XB130 mRNA in gastric cancer and paracancerous tissues was detected by real-time quantitative polymerase chain reaction.The relationship between the expression of XB130 and clinicopathological features of gastric cancer was analyzed.Results There were 26 cases of positive expression of XB130 protein and 46 cases of negative expression of XB130 protein among the 72 cases of gastric cancer tissues,and the positive expression rate was 36.1％ (26/72).There were 52 cases of positive expression of XB130 protein and 20 cases of negative expression of XB130 protein among the 72 cases of paracancerous tissues,and the positive expression rate was 72.2％ (52/72).The positive expression rate of XB130 protein in gastric cancer tissues was significantly lower than that in paracancerous tissues (x2 =16.200,P ＜ 0.05).The positive expression rate of XB130 protein in poorly and moderately differentiated gastric cancer tissues was significantly lower than that in well differentiated gastric cancer tissues (x2 =5.786,P ＜0.05).The positive expression rate of XB130 protein in gastric cancer tissues with lymph node metastasis was significantly lower than that in gastric cancer tissues without lymph node metastasis (x2 =4.281,P ＜0.05).The relative expression of XB130 mRNA in gastric cancer tissues and paracancerous tissues was 1.52 ±0.46 and 2.28-± 0.51 respectively,the expression of XB130 mRNA in gastric cancer tissues was significantly lower than that in paracancerous tissues (t =-21.744,P ＜0.05).The expression of XB130 mRNA in well differentiated gastric cancer tissues was significantly higher than that in poorly and moderately differentiated gastric cancer tissues (t =-13.982,P ＜ 0.05).The expression of XB130 mRNA in gastric cancer tissues with lymph node metastasis was significantly lower than that in gastric cancer tissues without lymph node metastasis (t =-19.906,P ＜ 0.05).The mean survival time in patients with high and low expression of XB130 mRNA was (37.040 ± 14.826) and (21.529 ± 11.789) months respectively,the survival time in patients with high expression of XB130 mRNA was significantly higher than that in patients with low expression of XB130 mRNA (t =9.121,P ＜0.05).Conclusion XB130 may be involved in the occurrence and development of gastric cancer,and it is associated with the differentiation,lymph node metastasis and survival time of patients with gastric cancer.

Clinical analysis of factors affecting colorectal adenoma recurrence after endoscopic resection / 复旦学报（医学版）

Objective To analyze the factors that might affect the recurrence after endoscopic resection of colorectal adenoma,we aim to provide a reference for the regular follow-up of colorectal adenoma after endoscopic resection.Methods In the Department of Gastroenterology,Huadong Hospital from Jan.,2013 to Dec.,2014,patients received endoscopic resection during hospital stay and postoperative follow-up colonoscopy.We collected their information of gender,age,smoking history,drinking history,hypertension,diabetes,fatty liver,cholecystectomy history,Helicobacter pylori (H.pylori) infection,related metabolic indicators,number of adenoma,size of adenoma,location of adenoma and pathology of adenoma.Multivariate and univariate analysis were performed by Logistic regression analysis to explore factors influencing the recurrence risk of colorectal adenoma.Results A total of 283 cases were enrolled.The recurrence rate of low-risk and high-risk adenoma was 39.3 ％ and 56.3 ％,respectively,and therate of all adenoma was 52.7％.Multivariate and univariate analysis both found that H.pylori infection (P＜0.001,OR:3.316 and 2.802,95％CI:1.869-5.884 and 1.660-4.728) and adenoma number (P＜0.001,OR:2.799 and 2.789,95％ CI:1.578-4.963 and 1.667-4.668) were risk factors for colorectal adenoma recurrence after endoscopic excision.Conclusions H.pylori infection and the number of base colorectal adenoma maybe associated with colorectal adenoma recurrence.

Role of CHOP-dependent endoplasmic reticulum stress signaling pathway in triptolide-induced apoptosis of A375 melanoma cells and its mechanisms / 中华皮肤科杂志

Objective To investigate the role of C/EBP homologous protein (CHOP)-dependent endoplasmic reticulum stress signaling pathway in triptolide-induced apoptosis of A375 melanoma cells,and to explore its mechanisms.Methods In vitro cultured human A375 melanoma cells were divided into several groups:experimental groups treated with triptolide at different concentrations of 12.5,25,50,100 and 200 nmol/L,and negative control group receiving no treatment.After 24-hour treatment,changes in the morphology of A375 cells were observed under a light microscope.After 24-,48-and 72-hour treatment,cell counting kit 8 (CCK8) assay was performed to evaluate the inhibitory effect of triptolide on cell proliferation.Flow cytometry was conducted to detect the apoptosis of A375 cells after annexin V-fluorescein isocyanate/propidium iodide double-staining,and transmission electron microscopy to observe the changes in the morphology of the endoplasmic reticulum.Western blot analysis was performed to determine the protein expression of glucose-regulated protein GRP78,protein kinase R-like endoplasmic reticulum kinase (PERK),phosphorylated PERK (p-PERK) and CHOP after 24-hour treatment,as well as to observe the changes in protein expression of GRP78 after treatment over time.Real-time fluorescencebased quantitative PCR (qPCR) was conducted to measure the mRNA expression of GRP78,PERK and CHOP.Results After the treatment with triptolide,A375 cells became long and thin,appeared fusiform with less cytoplasm,and varied in size.Their shape was irregular,and there were many protuberances on the cell surface.CCK8 assay showed that triptolide at different concentrations had inhibitory effects on the proliferation of A375 cells after 24-,48-and 72-hour treatment,and the inhibitory effects varied with the concentrations of triptolide and the duration of treatment (all P ＜ 0.05).The 50％ inhibitory concentration (IC50) of triptolide at 24,48 and 72 hours were 308,83 and 55 nmol/L respectively.The apoptosis rate of A375 cells was significantly higher in the 12.5-,25-,50-,100-and 200-nmol/L triptolide groups (10.3％ ± 0.1％,14.6％ ± 0.8％,17.4％ ± 0.7％,21.1％ ± 1.0％ and 29.5％ ± 1.1％,respectively) than in the negative control group (3.3％ ± 0.4％,all P ＜ 0.05).After 24-hour treatment with 200 nmol/L triptolide,damaged endoplasmic reticula were observed by using transmission electron microscopy.After 24-hour treatment with triptolide at different concentrations,the protein expression of GRP78,p-PERK,PERK and CHOP all gradually increased with the increase of triptolide concentrations (P ＜ 0.05).However,after 24-,48-and 72-hour treatment,the protein expression of GRP78 gradually decreased over time (P ＜ 0.05).qPCR showed that the mRNA expression of GRP78,PERK and CHOP gradually increased with the increase of triptolide concentrations after 24-hour treatment.Compared with the negative control group,all the experimental groups showed significantly higher mRNA expression of GRP78,PERK and CHOP (P ＜0.05) except the 12.5-nmol/L triptolide group with similar mRNA expression of PERK.Conclusion Triptolide can induce endoplasmic reticulum stress,and the apoptosis of A431 cells was induced by CHOP-dependent endo-plasmic reticulum stress along with the increase of triptolide concentrations and treatment duration.

Increased Endogenous Sulfur Dioxide Involved in the Pathogenesis of Postural Tachycardia Syndrome in Children: A Case-Control Study / 中华医学杂志(英文版)

<p><b>Background</b>The pathogenesis of postural tachycardia syndrome (POTS) remains unclear. This study aimed to explore the changes and significance of sulfur dioxide (SO) in patients with POTS.</p><p><b>Methods</b>The study included 31 children with POTS and 27 healthy children from Peking University First Hospital between December 2013 and October 2015. A detailed medical history, physical examination results, and demographic characteristics were collected. Hemodynamics was recorded and the plasma SOwas determined.</p><p><b>Results</b>The plasma SOwas significantly higher in POTS children compared to healthy children (64.0 ± 20.8 μmol/L vs. 27.2 ± 9.6 μmol/L, respectively, P < 0.05). The symptom scores in POTS were positively correlated with plasma SOlevels (r = 0.398, P < 0.05). In all the study participants, the maximum heart rate (HR) was positively correlated with plasma levels of SO(r = 0.679, P < 0.01). The change in systolic blood pressure from the supine to upright (ΔSBP) in POTS group was smaller than that in the control group (P < 0.05). The ΔSBP was negatively correlated with baseline plasma SOlevels in all participants (r = -0.28, P < 0.05). In the control group, ΔSBP was positively correlated with the plasma levels of SO(r = 0.487, P < 0.01). The change in HR from the supine to upright in POTS was obvious compared to that of the control group. The area under curve was 0.967 (95% confidence interval: 0.928-1.000), and the cutoff value of plasma SOlevel >38.17 μmol/L yielded a sensitivity of 90.3% and a specificity of 92.6% for predicting the diagnosis of POTS.</p><p><b>Conclusions</b>Increased endogenous SOlevels might be involved in the pathogenesis of POTS.</p>