Protective Effect of Magnesium Isoglycyrrhizinate on Ethanol-Induced Testicular Injuries in Mice

Objective:Ethanol treatment induces an increase in oxidative stress. As licorice compounds are potent antioxidants, our aim was to examine whether magnesium isoglycyrrhizinate attenuated lipid peroxidation, the major end-point of oxidative damage resulting from ethanol administration. Methods: Four groups(18 animals in each group) of male Kunming mice were used. The first group served as control and received 0.4 ml normal saline daily for 18 days orally. The second group of mice was given 56% ethanol at 16 ml/kg body weight per day for 18 days orally. The third group was given the same dose of ethanol and administrated magnesium isoglycyrrhizinate (15 mg/kg.d, i.p.) for 18 days. The fourth group was given the same dose of ethanol and administrated with magnesium isoglycyrrhizinate (45 mg/kg.d, i.p.) for 18 days. Twenty four hours after 9 days or 18 days of treatment the mice were sacrificed using 10% chloral hydrate. Sperm counts and motility in the epididymis were assessed. The lipid peroxidation and antioxidants of testicular mitochondria were also determined. The pathological changes of testicle tissue of the mice were observed by light microscopy. Results: Magnesium isoglycyrrhizinate effectively prevented the ethanol-induced seminiferous epithelium disorganization and degeneration of Sertoli cells and germ cells. Sperm counts and motility of the magnesium isoglycyrrhizinate treated groups were higher than those of the alcohol treated group, but were lower than those of the control group. The drug exhibited an ability to counteract ethanol induced oxidative challenge as it effectively reduced testicular malondialdehyde (MDA) and increased the activities of superoxide dismutase and glutathione peroxidase. Conclusion: Magnesium isoglycyrrhizinate is able to inhibit the ethanol-induced lipid peroxidation and has a protective effect against testicular oxidative injury.

A case of plasmablastic lymphoma of the liver without human immunodeficiency virus infection

Plasmablastic lymphoma(PBL)is a very rare B-cell lymphoproliferative disorder was with an aggressive clinical behavior that recently characterized by the World Health Organization.Although PBL is most commonly observed in the oral cavity of human immunodeficiency virus(HIV)-positive patients,it can also be observed at extra-oral sites in HIV-negative patients.Epstein-Barr virus(EBV)may be closely related the pathogenesis of PBL.PBL shows different clinicopathological characteristics between HIV-positive and-negative patients.Here,we report a case of PBL of the liver in a 79-yearold HIV-negative male.The patient died approximately1.5 mo after examination and autopsy showed that the main lesion was a very large liver mass.Histopathological examination of the excised lesion showed large-cell lymphoma with plasmacytic differentiation diffusely infiltrating the liver and involving the surrounding organs.The neoplastic cells were diffusely positive for CD30,EBV,Bob-1,and CD38.The autopsy findings suggested a diagnosis of PBL.To our knowledge,the present case appears to be the first report of PBL with initial presentation of the liver in a patient without HIV infection.

Factors associating with oxygenation of lower-limb muscle tissue in hemodialysis patients

AIM To evaluate the lower-limb muscle oxygenation in hemodialysis(HD) patients and identify the factors associating with muscle oxygenation.METHODS Sixty-seven HD patients(53 men and 14 women; mean age, 67.1 ± 1.2 years; mean HD duration, 5.6 ± 0.9 years) were recruited. In addition, 15 healthy individuals(nine men and six women; mean age, 38.2 ± 4.6 years) were recruited as the control group. Lower-limb muscle regional saturation of oxygen(rS O_2) was monitored on the lateral side of the gastrocnemius muscle before HD using an INVOS 5100C(Covidien Japan, Tokyo, Japan), which utilizes near-infrared spectroscopy. Here, we evaluated the association between lower-limb muscle rS O_2 and clinical parameters.RESULTS The r SO_2 values were significantly lower in patients undergoing HD than in healthy individuals(50.0%± 1.7% vs 76.8% ± 2.5%, P < 0.001). Lower-limb muscle r SO_2 showed significant positive correlations with diastolic blood pressure, blood urea nitrogen concentration, serum creatinine concentration, serum potassium concentration, serum inorganic phosphate concentration, and serum albumin concentration as well as negative correlation with HD duration. We conducted a multiple linear regression analysis using parameters that were significantly correlated with the lower-limb muscle r SO_2 in a simple linear regression analysis. Multiple regression analysis demonstrated that lowerlimb muscle r SO_2 was independently associated with serum inorganic phosphate(standardized coefficient: 0.27) and serum albumin concentrations(standardized coefficient: 0.24). In addition, there were no differences in lower-limb muscle r SO_2 between diabetic and nondiabetic HD patients. This study has several limitations. Firstly, its sample size was relatively small. Secondly, we could not evaluate the association between lowerlimb muscle r SO_2 and calculated nutritional markers, including normalized protein catabolic rate and body mass index, anthropometric measurements representing nutritional status, and the severity of protein-energy wasting. Finally, we did not routinely examine the arterial vascular status of HD patients without symptoms of peripheral artery disease. As such, it is possible that some HD patients with subclinical peripheral artery disease may have been included in this study.CONCLUSION In HD patients, the oxygenation of lower-limb muscle tissue was associated with serum inorganic phosphate and albumin concentrations, both of which represent nutritional status.

Correlation of peripheral blood IL-17A gene polymorphism with myocardial injury and MMPs/TIMPs balance in patients with viral myocarditis

Objective:To study the correlation of peripheral blood IL-17A gene polymorphism with myocardial injury and MMPs/TIMPs balance in patients with viral myocarditis.Methods:A total of 80 patients who were diagnosed with viral myocarditis in Dongguan Branch, Yan'an University Affiliated Hospital between September 2014 and September 2017 were selected as the VMC group of the research, and 100 healthy volunteers who received physical examination in Dongguan Branch, Yan'an University Affiliated Hospital during the same period were selected as the control group of the research. The peripheral blood was collected to determine the IL-17A gene rs2275913 locus polymorphism, and serum was collected to determine the contents of myocardial injury and MMPs/TIMPs indexes.Results: The proportion of IL-17A gene GG genotype of VMC group was lower than that of control group and the proportion of GA+AA genotype was higher than that of control group;serum IL-17, CK-MB, cTnI, sFas, MDA, PINP, ICTP, MMP2, MMP9, TIMP1 and TIMP2 contents of VMC group were significantly higher than those of control group, and serum IL-17, CK-MB, cTnI, sFas, MDA, PINP, ICTP, MMP2, MMP9, TIMP1 and TIMP2 contents of patients with GA+AA genotype in VMC group were higher than those of patients with GG genotype.Conclusion: The mutation of the allele G to A in the peripheral blood IL-17A gene rs2275913 locus of patients with viral myocarditis can aggravate myocardial injury and MMPs/TIMPs imbalance.

Effect of the Jianpibushen Prescription-containing serum on the colon cancer cell growth and angiogenesis

Objective: To study the effect of Jianpibushen Prescription-containing serum on the colon cancer cell growth and angiogenesis. Methods: SD male rats were taken and given intragastric administration of Jianpibushen Prescription, and arterial blood was collected after 1 week to prepare drug-containing serum;colon cancer cell line HCT116 was cultured and divided into two groups. The intervention group was treated with DMEM containing 10% drug-containing serum, and the control group was treated with DMEM containing 10% drug-free serum. After 24 h of treatment, the mRNA expression of proliferation genes, invasion genes and angiogenesis genes in cells were measured. Results: EZH2, USP22, Nanog, FAK, CDC37, HOXB9, TROP2, ELMO3, c-met, HIF-1 , VEGF and Ang-2 mRNA expression in intervention group of colon cancer cells were significantly lower than those in control group while ASPP2, MS4A12, TWEAK and Fn14 mRNA expression were significantly higher than those in control group. Conclusion: Jianpibushen Prescription-containing serum has inhibitory effect on the colon cancer cell proliferation and invasion as well as angiogenesis.

Correlation of serum Dickkopf-1 content with bone destruction, inflammatory response and oxidation reaction in patients with gouty arthritis

Objective:To study the correlation of serum Dickkopf-1 (DKK-1) content with bone destruction, inflammatory response and oxidation reaction in patients with gouty arthritis. Methods: A total of 40 patients with acute gouty arthritis who were treated in our hospital between 2013 and 2016 were selected as the group A of the study, 56 patients with asymptomatic hyperuricemia who were treated in our hospital during the same period were selected as the group B of the study, and 60 healthy volunteers who received physical examination in our hospital during the same period were selected as the control group of the study. The serum was collected to detect the contents of DKK-1, bone destruction indexes, inflammatory response indexes and oxidation reaction indexes.Results:Serum DKK-1, TRACP5b, RANKL,β-CTX, PGE2, sICAM-1, sVCAM-1, sCD14, MDA, 8-OHdG and 3-NT levels of group A and group B were significantly higher than those of control group while SOD and GSH-Px levels were significantly lower than those of control group;serum DKK-1, TRACP5b, RANKL,β-CTX, PGE2, sICAM-1, sVCAM-1, sCD14, MDA, 8-OHdG and 3-NT levels of group A were significantly higher than those of group B while SOD and GSH-Px levels were significantly lower than those of group B;serum DKK-1 level was positively correlated with TRACP5b, RANKL,β-CTX, PGE2, sICAM-1, sVCAM-1, sCD14, MDA, 8-OHdG and 3-NT levels, and negatively correlated with SOD and GSH-Px levels. Conclusion:Abnormally elevated DKK-1 in patients with gouty arthritis can induce articular bone destruction as well as inflammatory response and oxidative stress response activation.

A Systematic Review of RCTs and quasi-RCTs on Traditional Chinese Patent Medicines for Treatment of Chronic Hepatitis B

Traditional Chinese patent medicines (TCPMs) are widely used for treatment of chronic hepatitis B (CHB) in China. To estimate the overall effectiveness of TCPMs for CHB, we performed a systematic review of clinical reports designed as randomized controlled trials (RCTs). One hundred and thirty-eight available RCTs and quasi-RCTs on 62 TCPMs, involving 16,393 patients, were included. The methodological quality of these trials was generally "poor". Few trials (6.52%) reported the methods of randomization correctly. Another common problem was the lack of allocation concealment, proper blinding, and the reporting of lost cases and dropouts. Forty-two trials (30.43%) on 27 TCPMs reported some anti-viral effect of TCPMs. Others reported beneficial aspects, including improvements of liver function (79.71% of the studies), liver fibrosis (29.99%), and CHB symptoms (92.75%). Forty-one articles (29.71%) reported mild adverse events with TCPMs but these occurred infrequently. In summary, the outcome of the report on currently registered TCPMs may be biased due to poor methodology. The data from these trials, therefore, is too weak to use in forming a recommendation for treatment of CHB. Nevertheless, five drugs (Dan Shen agents, Da Huang Zhe Chong pill/capsule, Shuang Hu Qing Gan granule, Fu Zheng Hua Yu granule and Cao Xian Yi Gan capsule) appear to be more effective than the other TCPMs.

Appendicitis in double cecal appendix: Case report

Double cecal appendix is a rare anatomical variation. Approximately 100 cases have been reported worldwide. It is usually diagnosed incidentally during emergency appendectomies due to inflammatory processes in the cecal appendix. Case presentation: male, white, 36 years old, obese, presenting with pain in the lower abdomen for 24 h followed by nausea, vomiting and mild fever. He was subjected to additional tests, with the leukogram showing leukocytosis and abdominal ultrasonography depicting cecal appendix with thickened wall, locally associated with small quantities of liquid and intestinal loop obstruction. He underwent laparotomy, revealing acute appendicitis. Another intestinal loop obstruction was identified next to the ileum, leading to recognizing another cecal appendix after local dissection. Double appendectomy and segmental iliectomy were performed although not needed. Results of the anatomopathological examination of the surgical samples showed acute inflammation in the two cecal appendices. So, performing a routine retroperitoneal release and a complete cecum evaluation during such surgical procedures is recommended and suggested due to the possibility of not identifying a second cecal appendix.

High Glucose Promotes the CTGF Expression in Human Mesangial Cells via Serum and Glucocorticoid-induced Kinase 1 Pathway

The role of serum and glucocorticoid-induced kinase 1 (SGK1) pathway in the connective tissue growth factor (CTGF) expression was investigated in cultured human mesangial cells (HMCs) under high glucose. By using RT-PCR and Western blot, the effect of SGK1 on the CTGF expression in HMCs under high glucose was examined. Overexpression of active SGK1 in HMCs transfected with PIRES2-EGFP- S422D hSGK1 (SD) could increase the expression of phosphorylated SGK1 and CTGF as compared with HMCs groups transfected with PIRES2-EGFP (FP) under high glucose or normal glucose. Overexpression of inactive SGK1 in HMCs transfected with PIRES2-EGFP- K127N hSGK1 (KN) could decrease phosphorylated SGK1 and CTGF expression as compared with HMCs groups transfected with FP under high glucose. In conclusion, these results suggest that high glucose-induced CTGF expression is mediated through the active SGK1 in HMCs.

Schistosomiasis and Urothelial Bladder Carcinoma

Bladder cancer is the most common malignancy of the urinary tract and it affects four times more men than women. The relationship between bladder tumors and Schistosoma haematobium is well known, but only sporadic cases of bladder infection due to Schistosoma mansoni have been reported. Schistosoma mansoni infection causes an endemic disease in Brazil (schistosomiasis) and gastrointestinal disorders are very common, but disease of the urinary tract is atypical. The aim of this study was to describe a case of a patient presenting schistosomiasis (S. mansoni) and urothelial bladder carcinoma. In this case, a 37-year-old man with intermittent painless gross hematuria was investigated. Cystoscopy revealed a small pedunculated lesion in the bladder dome. Transurethral resection revealed urothelial carcinoma of the bladder, low degree, unrepresentative of the muscular layer of the bladder. After 30 days, a new transurethral resection was performed to sample acquisition of the muscular layer on the basis of the scar. Histopathology was negative for malignancy (Tumor Node Metastasis: TNM-T1). During this procedure, there was evidence of dark rounded lesion in the bladder dome. It was excised and the histopathology showed viable eggs of Schistosoma mansoni. The patient was treated orally with oxamniquine and remained in oncological monitoring with cystoscopy quarterly and serial clinical evaluation. This case reveals a rare finding of Schistosoma mansoni in the bladder and urothelial bladder carcinoma coexisting in the same patient.

Clinical Observation of Shuanghuang Shengbai Granule(双黄升白颗粒) on Prevention and Treatment of Myelosuppression Caused by Chemotherapy in Cancer Patients

Objective: To study the efficacy and safety of Shuanghuang Shengbai Granule(双黄升白颗粒, SSG), a traditional Chinese herbal medicine, on myelosuppression of cancer patients caused by chemotherapy. Methods: A total of 330 patients were randomly assigned to the treatment group(220 cases, analysed 209 cases) and the control group(110 cases, analysed 102 cases) with a 2:1 ratio by envelope method. The patients in the treatment group at the first day of chemotherapy started to take SSG for 14 days, while the patients in the control group took Leucogon Tablets. The changes of the blood routine, clinical symptoms and immune function in both groups were observed for safety and efficacy evaluation. Results: At the 7th day of chemotherapy, the white blood cells(WBCs) level in the treatment group was significantly higher than that in the control group(P<0.05). After treatment, the WBCs rate in the normal range accounted for 50.2% in the treatment group, the myelosuppression of WBCs and neutrophil were mainly grade Ⅰ, while 8.1% and 5.7% of patients emerged grade Ⅲ and grade Ⅳ myelosuppression, respectively. The incidence of myelosuppression of the treatment group was significantly lower than that of the control group(P<0.05). The total effective rate of Chinese medicine syndrome in the treatment group was significantly higher than that in the control group(84.2% vs. 72.5%, P<0.05). The immune cell levels in both groups were maintained in the normal range. Compared with that before treatment, the levels of CD3^+ and CD4^+ cells were significantly increased in the treatment group after treatment(P<0.05). The discrepancy of CD3^+ and CD4^+ cell activity before and after treatment in both groups were significantly different(P<0.05). No obvious adverse event occurred in both groups. Conclusion: SSG had a protection effect on bone marrow suppression, and alleviated the clinical symptoms together with clinical safety.

Human leukemia antigen-A0201-restricted epitopes of humanendogenous retrovirus W family envelope(HERV-W env)inducestrong cytotoxic T lymphocyte responses

Human endogenous retrovirus W family(HERV-W) envelope(env) has been reported to be related to several human diseases, including autoimmune disorders, and it could activate innate immunity.However, there are no reports investigating whether human leukemia antigen(HLA)-A~*0201^+restriction is involved in the immune response caused by HERV-W env in neuropsychiatric diseases. In the present study, HERV-W env-derived epitopes presented by HLA-A~*0201 are described with the potential for use in adoptive immunotherapy. Five peptides displaying HLAA~*0201-binding motifs were predicted using SYFEPITHI and BIMAS, and synthesized. A CCK-8 assay showed peptides W, Q and T promoted lymphocyte proliferation. Stimulation of peripheral blood mononuclear cells from HLA-A~*0201^+ donors with each of these peptides induced peptidespecific CD8^+ T cells. High numbers of IFN-γ-secreting T cells were also detectable after several weekly stimulations with W, Q and T. Besides lysis of HERV-W env-loaded target cells, specific apoptosis was also observed. These data demonstrate that human T cells can be sensitized toward HERV-W env peptides(W, Q and T) and, moreover, pose a high killing potential toward HERV-W env-expressing U251 cells. In conclusion, peptides W Q and T, which are HERV-W env antigenic epitopes, have both antigenicity and immunogenicity, and can cause strong T cell immune responses. Our data strengthen the view that HERV-W env should be considered as an autoantigen that can induce autoimmunity in neuropsychiatric diseases, such as multiple sclerosis and schizophrenia. These data might provide an experimental foundation for a HERV-W env peptide vaccine and new insight into the treatment of neuropsychiatric diseases.

Human endogenous retrovirus W env increases nitric oxide production and enhances the migration ability of microglia by regulating the expression of inducible nitric oxide synthase

Human endogenous retrovirus W env(HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis(MS). These diseases are accompanied by immunological reactions in the central nervous system(CNS). Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter – nitric oxide(NO). NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases. In this study, we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env. Moreover, HERV-W env increased the expression and function of human inducible nitric oxide synthase(hi NOS) and enhanced the promoter activity of hi NOS. Microglial migration was also enhanced. These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS. Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases, including neuroinflammatory diseases, stroke, and neurodegenerative diseases.

Safety and efficacy of Tongkuaixiao ointment in reliving cancer-induced pain: a multicenter double-blind placebo-controlled randomized trial

OBJECTIVE: To evaluate the safety and efficacy of Tongkuaixiao ointment(TKXO) in treating moderate-to-severe cancer induced somatalgia.METHODS: Totally 130 patients with moderateto-severe cancer induced somatalgia were randomly divided into a TKXO group and a control group.The patients were treated with either TKXO applied externally or placebo, with opioid analgesics orally at the same time. Observation parameters were included numerical rating scale(NRS) scores,analgesic efficacy, initiation effective time, persistent analgesic time, equivalent morphine dose,National Comprehensive Cancer Network(NCCN)grade in Impact of Pain Measurement Scores, and safety and satisfaction extent investigation.RESULTS: NRS scores and NCCN grade in Impact of Pain Measurement Scores decreased significantly after 5-days' treatment in the two groups(P <0.0001). Compared to the control group, initiation effective time was significantly shorter(P < 0.05)and persistent analgesic time was significantly longer(P < 0.01), equivalent oral morphine doses of the first day and the whole treatment course were significantly decreased in the TKXO treatment group(P < 0.01 or P < 0.05). No obvious adverse effects were found in the TKXO group.CONCLUSION: TKXO combined with opioid analgesics possesses the advantages of high efficacy,fast action, long persistent action, safety and convenience in use, and it can reduce the dose of opioid.

肝移植术后患者口服他克莫司引起的肝窦梗阻综合征

Introduction Hepatic sinusoidal obstruction syndrome(HSOS)is a hepatic vascular disease characterized by injury of the endothelial cells in the sinusoidal hepatic and interlobular veins,intra-hepatic congestion,liver dysfunction,and portal hypertension[1].In Western countries,HSOS is often associated with myeloablative regimens used for hematopoietic stem-cell transplantation,while,in China,it is often associated with oral intake of Gynura segetum plants that contain pyrrolidine alkaloids[2].In addition,new-onset HSOS after solid-organ transplantation has received increasing attention[3-8].

异常的CD39/CD73/腺苷通路导致慢性乙型肝炎患者B细胞超活化和疾病进展

背景:乙肝病毒(HBV)感染患者B细胞超活化的机制尚不明确。本研究旨在评估CD39/CD37/腺苷通路在慢性乙型肝炎(CHB)患者中的临床特点。方法:我们检测了202例HBV感染患者B细胞CD39和CD73表达及腺苷产生情况。CpG+CD40配体刺激B细胞后,阻断或激活CD39/CD73/腺苷通路,然后通过流式细胞术检测B细胞活化表型结果:在具有高HBV DNA载量,HBeAg阳性,高HBsAg水平以及肝脏炎症活跃的CHB患者中,外周血B细胞的CD39和CD73表达降低,并且在HBeAg血清转化或HBsAg降低的完全应答者中逐步恢复。尽管进行了有效的抗病毒治疗,但完全应答者中活化记忆B细胞亚群和组织样记忆B细胞亚群的CD39和CD73表达并未增加。此外,在炎性肝脏中,肝内B细胞的CD39和CD73表达降低。在体外,CHB患者的B细胞显示产生CD39/CD73依赖性细胞外腺苷的能力明显降低。阻断腺苷生成后B细胞活化标志物表达增加。相反,二甲双胍通过调节腺苷酸活化蛋白激酶,激活CD39/CD73/腺苷通路,从而使B细胞活化标志物表达显著降低。结论:B细胞中CD39和CD73表达下调可导致CHB患者的高病毒负荷,加重肝脏炎性反应,并影响抗病毒疗效。异常的CD39/CD73/腺苷通路导致B细胞超活化。使用二甲双胍调节CD39/CD73/腺苷通路可能作为一种能够逆转HBV诱导的免疫发病机制的治疗选择。