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Endometrial carcinoma is one of the most common gynecologic malignancies. CXCL17-CXCR8 (GPR35) axis is reported to play an indispensability role in tumors. Our purpose is to screen possible prognostic and immune-related factors in endometrial carcinoma by detecting the mRNA and protein expression of CXCL17 and CXCR8. We use the qRT-PCR method to test the mRNA expression of CXCL17 and CXCR8 in 35 pairs of endometrial carcinoma and adjacent tissue. The protein expression of CXCL17 and CXCR8 in 30 cases of normal proliferative endometrium, 30 cases of endometrial atypical hyperplasia and 50 cases of endometrial carcinoma was detected by tissue microarray immunohistochemistry. There was no significant difference in the positive expression rate between endometrial adenocarcinoma tissue and endometrial atypical hyperplasia tissue (P0.05). But significantly better than normal proliferative tissue (P0.001). Correlation analysis of CXCR8 and CXCL17 in endometrial carcinoma showed a positive correlation (r = 0.9123, P0.0001). For patients with endometrial cancer, the overall survival (OS) of patients with high CXCL17 expression was significantly higher than that low CXCL17 expression (log-rank test, P0.0001), whereas CXCR8 had no statistical significance. But the expression of CXCR8 is an independent prognostic factor of OS in endometrial carcinoma patients. Our study showed that CXCL17 and CXCR8 may be involved in the occurrence and development of endometrial cancer. High expression of CXCL17 may be used as a biomarker for predicting survival. Because CXCL17 and CXCL18 are related to lymphocytes and immune regulation, they are expected to become potential targets for immunotherapy.

Background The traditional Chinese medicine formula Si-Jun-Zi-Tang (SJZT) has a long history of application in the treatment of functional dyspepsia (non-ulcer dyspepsia, FD)-like symptoms. SJZT-based therapies have been claimed to be beneficial in managing FD. This study aimed to assess the efficacy and safety of SJZT-based therapies in treating FD by meta-analysis. Methods Systematic searches for RCTs were conducted in seven databases (up to February 2019) without language restrictions. Data were analyzed using Cochrane RevMan software version 5.3.0 and Stata software version 13.1, and reported as relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CIs). The primary outcome was response rate and the secondary outcomes were gastric emptying, quality of life, adverse effects and relapse rate. The quality of evidence was evaluated according to criteria from the Cochrane risk of bias. Results A total of 341 potentially relevant publications were identified, and 12 RCTs were eligible for inclusion. For the response rate, there was a statically significant benefit in favor of SJZT-based therapies (RR = 1.23; 95% CI 1.17 to 1.30). However, the benefit was limited to modified SJZT (MSJZT). The relapse rate of FD patients received SJZT-based therapies was lower than that of patients who received conventional medicines (OR = 0.23; 95% CI 0.10 to 0.51). No SJZT-based therapies-related adverse effect was reported. Conclusion SJZT-based prescriptions may be effective in treating FD and no serious side-effects were identified, but the effect on response rate appeared to be limited to MSJZT. The results should be interpreted with caution as all the included studies were considered at a high risk of bias. Standardized, large-scale and strictly designed RCTs are needed to further validate the benefits of SJZT-based therapies for FD management. Trial registration Systematic review registration: [PROSPERO registration: CRD42019139136].

To investigate the clinical features of acute myeloid leukemia patients with hemophagocytic syndrome.The clinical data of 2 patients with acute myeloid leukemia complicated with hemophagocytic syndrome were collected, and the clinical characteristics and treatment outcomes were analyzed.There were two patients with acute myeloid leukemia, including 1 male and 1 female，aged for 67 and 40 years old，respectively. Hemophagocytic syndrome occurred in one patient after induction therapy for acute myeloid leukemia and one patient after consolidation therapy. Both of the patients with hemophagocytic syndrome showed fever, hemocytopenia, high ferritin, high titer sCD25 levels and hemophagocytes in bone marrow. After achieved anti-infection, glucocorticoid, human immunoglobulin and etoposide regimens treatment, hemophagocytic syndrome was controlled in both of the two patients. One patient failed to induce acute myeloid leukemia and one patient achieved complete remission.Acute myeloid leukemia complicated with hemophagocytic syndrome is rare. Early identification, early anti-infection combined with HLH94 regimen can control hemophagocytosis and improve prognosis.急性髓系白血病合并噬血细胞综合征患者的临床分析.探讨急性髓系白血病合并噬血细胞综合征患者的临床特征.收集2例急性髓系白血病合并噬血细胞综合征患者的临床资料，分析其临床特征、治疗转归.2例急性髓系白血病患者，其中男性1例，女性1例，年龄分别为67和40岁。1例患者噬血细胞综合征发生在急性髓系白血病诱导治疗后，另1例患者发生在巩固治疗后。2例患者发生噬血细胞综合征时均有发热、血细胞减少、铁蛋白高、高滴度sCD25水平及骨髓见噬血细胞。经积极抗感染、糖皮质激素、人免疫球蛋白和依托泊苷方案治疗，2例患者噬血细胞综合征得到控制，其中1例患者急性髓系白血病诱导失败，1例患者急性髓系白血病获得持续完全缓解.急性髓系白血病合并噬血细胞综合征临床少见，应早期识别，早期抗感染联合HLH94方案治疗，控制噬血，改善患者预后.

This study aimed to determine whether and how the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide affects the chemoresistance and chemosensitivity of pancreatic cancer cells to gemcitabine in vitro and in vivo. The GLP-1R and protein kinase A (PKA) levels were compared between the human pancreatic cancer cell line PANC-1 and the gemcitabine-resistant cell line PANC-GR. The in vitro effects of liraglutide on the cell proliferation and apoptosis as well as the nuclear factor-kappa B NF-κB expression levels of PANC-GR cells were evaluated. In addition, a mouse xenograft model of human pancreatic cancer was established by s.c. injection of PANC-1 cells, and the effects of liraglutide on the chemosensitivity were evaluated in vitro and in vivo. In contrast to PANC-1 cells, PANC-GR cells exhibited lower expression levels of GLP-1R and PKA. Incubation with liraglutide dose dependently inhibited the growth, promoted the apoptosis, and increased the expression of GLP-1R and PKA of PANC-GR cells. Similar effects of liraglutide were observed in another human pancreatic cancer cell line MiaPaCa-2/MiaPaCa-2-GR. Either the GLP-1R antagonist Ex-9, the PKA inhibitor H89, or the NF-κB activator lipopolysaccharide (LPS) could abolish the antiproliferative and proapoptotic activities of liraglutide. Additionally, each of these agents could reverse the expression of NF-κB and ABCG2, which was decreased by liraglutide treatment. Furthermore, liraglutide treatment increased the chemosensitivity of pancreatic cancer cells to gemcitabine, as evidenced by in vitro and in vivo experiments. Thus, GLP-1R agonists are safe and beneficial for patients complicated with pancreatic cancer and diabetes, especially for gemcitabine-resistant pancreatic cancer.

Objective To investigate the effect of psychological intervention on the prognosis of patients with C4 dislocation and spinal cord injury. Methods We investigated target patients admitted between 2010 and 2018. Patients’ mental state, quality of life and neurological function at different time points were evaluated to examine the relationship between psychological intervention and recovery and prognosis of acute and critical spinal cord injury. Results All patients showed improvements in clinical symptoms, neurological function and quality of life. Psychological intervention significantly improved Zung Self-Rating Anxiety Scale score, Zung Self-Rating Depression Scale score and SF-36 Mental Component Summary score within 3 months. Japanese Orthopaedic Association neurological function score and SF-36 Physical Component Summary score were significantly improved after 1-year follow-up. Psychological intervention did not improve 2-year survival. Conclusion Timely and professional psychological intervention can eliminate the psychological disorders of C4 dislocation patients with spinal cord injury. This has a positive effect on their quality of life and prognosis.

Primary liver cancer is a lethal cancer. The phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway has been implicated in the pathogenesis of liver cancer. Gomisin N (GN), a lignan isolated from the dried fruits of Schisandra chinensis (Turca.) Baill., has been reported to reduce viability of, and induce apoptosis in, HepG2 liver cancer cells. In preadipocytes, GN was found to inhibit Akt activity. In the present study, Akt signaling-related anti-liver cancer mechanisms of GN were investigated. We confirmed that GN reduces cell viability of, and triggers apoptosis in, more liver cancer cell lines. Mechanistic studies revealed that GN lowers protein levels of phospho-PI3K (p85 tyrosine (Tyr)458), phospho-Akt (serine (Ser)473), and Akt downstream molecules Mcl-1 in HepG2 and HCCLM3 cells. Meanwhile, GN activates mTOR and inhibits ULK1 (a negative downstream effector of mTOR) activities. Activation of mTOR has been reported to suppress ULK1 activity and repress autophagy. Indeed, we observed that GN inhibits autophagy in liver cancer cells. In summary, we for the first time demonstrated that GN inhibits the PI3K-Akt pathway and regulates the mTOR-ULK1 pathway in liver cancer cells.

Investigate the effect of mild hypothermia on serum inflammatory factor HMGB1 of brain-dead donors, and its significance for renal transplantation recipients.In our hospital between January 2018 and January 2019 up to the standard of brain death donor (aged 18 to 65 years old) prospective cohort study, brain death donor were randomly divided into mild hypothermia group and the non-mild hypothermia group. Serum were collected from donor at different periods, and enzyme-linked immunoassay (ELISA) was used to determine the serum HMGB1 concentration to compare the difference between the 2 donor groups. The early recovery of renal function after renal transplantation was followed up, and the incidence of delayed graft function (DGF) and early recovery of renal function were compared between the 2 groups. The correlation between donor HMGB1 and recipient DGF was analyzed.Between 17 donors in the mild hypothermia group and 17 in the non-mild hypothermia group, there were no statistically significant differences in the age, perioperative urine volume and ICU stay between the 2 groups. After mild hypothermia treatment, serum HMGB1 levels of brain death donors were significantly decreased. While in non-mild hypothermia brain death donor group without treatment, serum HMGB1 was significantly increased. There were no statistically significant differences in age and preoperative creatinine between the 2 recipient groups, including 33 patients in the mild hypothermia group and 34 patients in the non-mild hypothermia group. DGF incidence was lower in mild hypothermia group comparing with non-mild hypothermia group with statistical significance. The levels of HMGB1 from donor before procurement is correlated with the occurrence of DGF of the recipient.Mild hypothermia therapy can reduce the levels of serum HMGB1, improve the function of donor organs. The levels of HMGB1 before donor procurement can be used to predict the occurrence of DGF in kidney transplant recipients. Our study shows that HMGB1 can be potentially used as therapeutic target of early intervention for brain death donors. Furthermore, mild hypothermia therapy can be applied in the maintenance of brain death donors for kidney transplant recipient to improve the successful rate of transplantation.

Fibroblast-like synoviocytes (FLS) play a pathogenic role in rheumatoid arthritis (RA). STAT3 signaling is activated in FLS of RA patients (RA-FLS), which in turn causes RA-FLS hyperproliferation. RL is a traditional remedy for treating inflammatory diseases in China. It comprises Rosae Multiflorae Fructus and Lonicerae Japonicae Flos. A standardized ethanolic extract of RL (RLE) has been shown to exert anti-arthritic effects in collagen-induced arthritis (CIA) rats. Some constituents of RLE were reported to inhibit JAK2/STAT3 signaling in rat FLS. Here, we determined whether RLE inhibits FLS hyperproliferation, and explored the involvement of STAT3 signaling in this inhibition. In joints of CIA rats, RLE increased apoptotic FLS. In IL-6/sIL-6R-stimulated RA-FLS, RLE reduced cell viability and evoked cell apoptosis. In synovial tissues of CIA rats, RLE lowered the protein level of phospho-STAT3. In IL-6/sIL-6R-stimulated RA-FLS, RLE inhibited activation/phosphorylation of STAT3 and JAK2, decreased the nuclear localization of STAT3, and downregulated protein levels of Bcl-2 and Mcl-1. Over-activation of STAT3 diminished RLE’s anti-proliferative effects in IL-6/sIL-6R-stimulated RA-FLS. In summary, RLE inhibits hyperproliferation of FLS in rat and cell models, and suppression of STAT3 signaling contributes to the underlying mechanisms. This study provides further pharmacological groundwork for developing RLE as a modern anti-arthritic drug.

To investigate the clinical characteristics and risk factors of low fibrinogenemia (LF) induced by hemocoagulase.Clinical data of 57 patients with hypofibrinogenemia (LF group) treated with hemocoagulase during Jan.2015 to Oct. 2018 in our hospittal were analyzed retrospectively. The control group consisted of 60 patients who did not develop hypofibrinogenemia treated with hemocoagulase. The clinical characteristics were compared between these two groups, the univariate analysis and multivariate analysis were also performed.In LF group, the fibrinogenemia occurred on 5.4(σ=1.067) days after use of hemocoagulase，with the main manifestations as bleeding from the operation or wound site, the decrease of fibrinogen (0.694 g/L,σ=0.211), the increase of D-dimer (4.468μg/mL,σ=1.442) and the recovery of Fib on the day 3.93 (σ=0.563) after drug withdrawal. There were significant differences in age, sex, primary disease, origin of snake venom, course of treatment, complication of hepatic and renal insufficiency and route of administration between the 2 groups (P＜0.05). Multivariate logistic regression analysis showed that age(P=0.007,OR=11.248), course of treatment (P＜0.001,OR=72.104) and route of administration (P=0.049,OR=13.389) were risk factors for hypofibrinogenemia.The use of hemocoagulase should be vigilant against the occurrence of hypofibrinogenemia. Old age, long course of treatment and the intravenous administration may increase the risk of hypofibrinogenemia.蛇毒血凝酶致低纤维蛋白原血症的临床特征及危险因素分析.探讨蛇毒血凝酶致低纤维蛋白原血症（low fibrinogenemia，LF）的临床特征及危险因素.回顾性分析2015年1月至2018年10月于福建医科大学附属第二医院住院期间应用蛇毒血凝酶发生低纤维蛋白原血症57例患者（LF组）的临床资料，选取同期应用蛇毒血凝酶未发生低纤维蛋白原血症的60例患者作为对照组。比较两组患者的临床特征，并进行单因素及多因素分析.LF组患者低纤维蛋白原血症发生于用药后（5.4±1.1）d，主要表现为手术或创伤部位渗血、纤维蛋白原（Fib）降至0.694±0.211 g/L、D-二聚体升至4.468±1.442 μg/ml，停药后（3.9±0.6）d Fib恢复正常。2组在年龄、性别、原患疾病、蛇毒来源、疗程、合并肝肾功能不全和给药途径方面比较差异有统计学意义（均P＜0.05）。多因素Logistic回归分析显示，年龄（P=0.007，OR=11.248）、疗程（P＜0.001，OR=72.104）和给药途径（P=0.049，OR=13.389）为发生低纤维蛋白原血症的高危因素.应用蛇毒血凝酶应警惕低纤维蛋白原血症的发生。老年、疗程长、静脉给药可增加低纤维蛋白原血症的发病风险.

Malignant melanoma is aggressive and has a high mortality rate. Toll-like receptor 4 (TLR4) has been linked to melanoma growth, angiogenesis and metastasis. However, signal transduction mediated by TLR4 for driving melanoma progression is not fully understood. Signal transducer and activator of transcription 3 (STAT3) has been identified as a major oncogene in melanoma progression. We found: that TLR4 expression positively correlates with activation/phosphorylation of STAT3 in human melanoma samples; that TLR4 ligands activate STAT3 through MYD88 and TRIF in melanoma cells; and that intratumoral activation of TLR4 increases STAT3 activation in the tumor and promotes tumor growth, angiogenesis, epithelial–mesenchymal transition (EMT) and the formation of an immunosuppressive tumor microenvironment in mice. Further, we found that the effects mediated by activating TLR4 are weakened by suppressing STAT3 function with a dominant negative STAT3 variant in melanoma. Collectively, our work identifies STAT3 activation as a key event in TLR4 signaling-mediated melanoma progression, shedding new light on the pathophysiology of melanoma.

IntroductionGastric cancer is the fifth most common cancer worldwide and the detection rate of proximal gastric cancer has been increasing. Currently, surgical resection using gastrectomy and proper perigastric lymphadenectomy is the only treatment option to enhance the survival rate of patients with gastric cancer. Laparoscopic total gastrectomy (LTG) is increasingly performed for adenocarcinoma of the oesophagogastric junction. However, totally LTG (TLTG) is only performed by a few surgeons due to difficulty associated with oesophagojejunostomy (OJ), in which there is no consensus on a standardised anastomosis technique. We propose a randomised trial to compare functional end-to-end anastomosis (FETE) and side-to-side anastomosis (Overlap) for OJ.Methods and analysisA prospective, randomised, open-label, single-centre, interventional trial has been designed to evaluate the quality of life (QoL) outcomes and safety of FETE and Overlap, with a 1-year follow-up as the primary endpoint. The trial began in 2020 and is scheduled to enrol 96 patients according to a previous sample size calculation. Patients were randomly allocated to the FETE or Overlap groups with a follow-up of 1 year to assess QoL after the procedure. All relevant clinical data including biological markers were collected. The primary indicator is the D-value between the postoperative and preoperative QoL. Student’s t-tests will be used to compare continuous variables, while χ2 tests or Fisher’s exact tests will be used to compare categorical variables. Statistical analysis will be performed with SPSS V.23.0 statistical software. A pEthics and disseminationThis study has been approved by the Hospital Institutional Review Board of Huashan Hospital, Fudan University (2020-1055). The results will be submitted for publication in peer-reviewed journals.Trial registration numberChiCTR2000035583.

Objective To evaluate the prevalence of breast tenderness in a population treated with menopausal hormone therapy (MHT) or Cimicifuga foetida extract. Methods A prospective, randomized, controlled trial was conducted. Ninety-six postmenopausal women were randomly assigned to three groups: group A, 1 mg estradiol valerate daily plus 4 mg medroxyprogesterone acetate (MPA), days 19-30; group B, 1 mg estradiol valerate daily plus 100 mg micronized progesterone (MP), days 19-30; group C, 100 mg C. foetida extract daily. Breast tenderness was evaluated daily for 12 months. Results Seventy-three patients completed the study. Group A had the highest prevalence of breast tenderness, while group C had the lowest. More than 50% of all participants reported no symptoms throughout the period. The participants in group A experienced a sharp increase in breast tenderness after treatment, but decreased after 1 month. No significant decline was found in the duration of pain in group B. The patients in group C reported no remarkable changes after 1 month. Compared to estrogen only, estrogen plus MPA/MP led to a higher incidence of prolonged breast symptoms. Conclusions Compared to MHT groups, C. foetida extract had the lowest prevalence of breast tenderness. Most participants experienced mild or no symptoms.

Background: Chronic kidney disease (CKD) with moderate-to-severe renal dysfunction usually exhibits an irreversible course, and available treatments for delaying the progression to end-stage renal disease are limited. This study aimed to assess the efficacy and safety of the traditional Chinese medicine, Niaoduqing particles, for delaying renal dysfunction in patients with stage 3b-4 CKD. Methods: The present study was a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial. From May 2013 to December 2013, 300 CKD patients with an estimated glomerular filtration rate (eGFR) between 20 and 45 ml·min −1 ·1.73 m −2 , aged 18–70 years were recruited from 22 hospitals in 11 Chinese provinces. Patients were randomized in a 1:1 ratio to either a test group, which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks, or a control group, which was administered a placebo using the same methods. The primary endpoints were changes in baseline serum creatinine (Scr) and eGFR after completion of treatment. The primary endpoints were analyzed using Student's t -test or Wilcoxon's rank-sum test. The present study reported results based on an intention-to-treat (ITT) analysis. Results: A total of 292 participants underwent the ITT analysis. At 24 weeks, the median (interquartile range) change in Scr was 1.1 (−13.0–24.1) and 11.7 (−2.6–42.9) μmol/L for the test and control groups, respectively ( Z = 2.642, P = 0.008), and the median change in eGFR was −0.2 (−4.3–2.7) and −2.2 (−5.7–0.8) ml·min −1 ·1.73 m −2 , respectively ( Z = −2.408, P = 0.016). There were no significant differences in adverse events between the groups. Conclusions: Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD. This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction. Trial Registration: Chinese Clinical Trial Register, ChiCTR-TRC-12002448; http://www.chictr.org.cn/showproj.aspx?proj=7102 .

This study aimed to investigate the safety and efficacy of Xiangshao granules for treating emotional disorders in perimenopausal and postmenopausal women. The current investigation was a double-blind, randomized, placebo-controlled, multicenter trial that included 300 perimenopausal and postmenopausal Chinese women aged 40–60 years. Participants received either a placebo (n = 150) or Xiangshao granules (n = 150) for 8 weeks. Outcome measures included Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA) scores, which were assessed at baseline, 4 weeks, and 8 weeks. The primary efficacy variables were changes in HAMD and HAMA scores after 8 weeks. After 8 weeks, the mean HAMD scores decreased from 15.0 to 7.9 in the Xiangshao group and from 16.3 to 10.0 in the placebo group, and the respective mean reductions in HAMA scores were from 16.0 to 8.5 and from 17.1 to 10.9. Clinical improvements in symptoms of both depression and anxiety after 8 weeks differed significantly in the two groups (p Xiangshao granules can relieve symptoms of depression and anxiety significantly and safely.

The purpose of the study was to evaluate the immunity effects after vaccinating different doses and frequencies of hepatitis B vaccines by calculating the seroconversion rates of HBsAb in patients with lymphoma. Clinical data of 315 patients from January 2010 to August 2018 were analyzed. According to different doses and frequencies, the patients were divided into three groups: low-dose group, high-dose group, and high-dose and high-frequency group. The highest seroconversion rate of HBsAb was 82.3% in the high-dose and high-frequency group (

Aims Melanoma is lethal. Constitutively active signal transducer and activator of transcription 3 (STAT3) has been proposed as a pathogenic factor and a therapeutic target of melanoma. Brevilin A, a sesquiterpene lactone isolated from Centipeda minima (L.) A. Br. et Aschers., has been shown to exert antineoplastic effects and inhibit the STAT3 pathway in nasopharyngeal, lung, prostate and breast cancer cells. This study aimed to determine whether brevilin A has anti-melanoma effects, and whether STAT3 signaling is involved in the effects. Main methods A mouse A375 xenograft model, as well as A375 and A2058 cell models were employed to assess the in vivo and in vitro anti-melanoma effects of brevilin A. A375 cells stably expressing STAT3C, a constitutively active STAT3 mutant, were used to determine the role of STAT3 signaling in brevilin A's anti-melanoma effects. Key findings Intraperitoneal injection of brevilin A dose-dependently inhibited melanoma growth in mice and suppressed STAT3 phosphorylation in the tumors. In cultured cells, brevilin A reduced cell viability, induced apoptosis, suppressed migration and invasion, decreased protein levels of phospho-JAK2 (Y1007/1008) and phospho-STAT3 (Tyr705), and restrained STAT3 nuclear localization. STAT3 over-activation diminished brevilin A's effects on cell viability and migration. Collectively, brevilin A exerts anti-melanoma effects and these effects are at least in part attributed to the inhibition of the JAK2/STAT3 pathway. Significance Our findings provide a pharmacological basis for developing brevilin A as a new phytotherapeutic agent against melanoma.

The aim of this paper was to investigate the effect of SIRT1/TSC_2 signal axis on leukemia stem cell senescence induced by ginsenoside Rg_1. CD34~+CD38~- leukemia stem cells(CD34~+CD38~-LSCs) was isolated by magnetic cell sorting(MACS) and divided into two groups. The control group cells were routinely cultured, 40 μmol·L~(-1) ginsenoside Rg_1 was added to the control group for co-culture in Rg_1 group. The effect of Rg_l to induce CD34~+CD38~-LSCs senescence were evaluated by senescence-associated β-Galactosidase(SA-β-Gal) staining, cell cycle assay, CCK-8 and Colony-Assay. The expression of senescence associated SIRT1, TSC_2 mRNA and protein was examined by Real-time fluorescence quantitative PCR(FQ-PCR) and Western blot. The results showed that the CD34~+CD38~-LSCs could effectively be isolated by MACS, and the purity of CD34~+CD38~-LSCs is up to(95.86±3.04)%. Compared with the control group, the percentage of positive cells expressed SA-β-Gal in the Rg_1 group is increased, the senescence morphological changes were observed in the CD34~+CD38~-LSCs in the Rg_1 group. The proliferation inhibition rate and the number of cells entered G_0/G_1 phase in the Rg_1 group were increased, but the colony-formed ability was decreased, Rg_1 could significantly inhibit the proliferation and self-renewal ability of CD34~+CD38~-LSCs. The expression of SIRT1 and TSC_2 mRNA and protein were down regulated in the Rg_1 group compared with the control group. Our research implied that Rg_1 may induce the senescence of CD34~+CD38~-LSCs and SIRT1/TSC_2 signal axis plays a significant role in this process.

Resveratrol is a natural polyhydroxy trans-stilbene product with many biological activities. One of the most striking biological activities of it is its anti-aging potential. Resveratrol can exhibit anti-aging activity via a variety of signaling pathways, however, the repair effect of it on kidney and brain injury in aging mice induced by d-galactose and its regulation on klotho gene expression have not been reported. Herein, the anti-aging activity of resveratrol and its effect on the repair of kidney and brain injuries in d-galactose-induced aging mice, as well as its regulation of klotho gene expression in these two tissues were investigated. The results indicated that resveratrol could significantly increase the aged cell viability and improve the pathological status of aging mice via inhibiting the formation of malondialdehyde and enhancing the activities of superoxide dismutase and catalase. The histological analysis suggested that resveratrol could remarkably repair the damages of kidney and brain tissues in aging mice. Moreover, PCR and western blot have shown that resveratrol could obviously increase the anti-aging klotho gene expression in the above tissues. The data in this paper further revealed and enriched the anti-aging mechanism of resveratrol, and the methods established in this study can be used as a tool to evaluate the anti-aging activity of drugs to a certain extent.

In this work, the inhibitory effect of two isoflavonoids including daidzein and genistein on trypsin and their binding mechanism were determined by spectroscopic and molecular docking approaches. The results indicated that both daidzein and genistein reversibly inhibited trypsin in a competitive manner with IC50 values of 68.01×10(-6)molL(-1) and 64.70×10(-6)molL(-1) and Ki values of 62.12×10(-6)molL(-1) and 59.83×10(-6)molL(-1), respectively. They could spontaneously bind with trypsin mainly through hydrophobic force and electrostatic interactions with a single binding site. Analysis of circular dichrosim spectra and molecular docking revealed that both isoflavonoids bound directly into the catalytic cavity and the microenvironment and secondary structure of trypsin were changed in this process, which caused the inhibition of trypsin activity. All these experimental results and theoretical data in this work would be help in understanding the mechanism of inhibitory effects of daidzein and genistein against trypsin and the potential of isoflavonoid to relieve symptoms of pancreatitis.

Increasing amounts of evidence has demonstrated that T2DM (Type 2 Diabetes Mellitus) patients have increased susceptibility to CRC (colorectal cancer). As HHEX is a recognized susceptibility gene in T2DM, this work was focused on two SNPs in HHEX, rs1111875 and rs7923837, to study their association with CRC. T2DM patients without CRC (T2DM-only, n=300), T2DM with CRC (T2DM/CRC, n=135), cancer-free controls (Control, n=570), and CRC without T2DM (CRC-only, n=642) cases were enrolled. DNA samples were extracted from the peripheral blood leukocytes of the patients and sequenced by direct sequencing. The χ2 test was used to compare categorical data. We found that in T2DM patients, rs1111875 but not the rs7923837 in HHEX gene was associated with the occurrence of CRC (p= 0.006). for rs1111875, TC/CC patients had an increased risk of CRC (p=0.019, OR=1.592, 95%CI=1.046-2.423). Moreover, our results also indicated that the two variants of HEEX gene could be risk factors for CRC in general population, independent on T2DM (p< 0.001 for rs1111875, p=0.001 for rs7923837). For rs1111875, increased risk of CRC was observed in TC or TC/CC than CC individuals (p

Nowadays, many big cities are suffering from heavy air pollution and continuous haze weather. Compared with the threat on physical health, the influence of haze on people&rsquo, s mental health is much less discussed in the current literature. Emotion is one of the most important indicators of mental health. To understand the negative impact of haze weather on the emotion of the people, we conducted an investigation based on historical weather records and microblog data in Tianjin, China. Specifically, an emotional thesaurus was generated with a microblog corpus collected from sample data. Based on the thesaurus, the public emotion under haze was statistically described. Then, through correlation analysis and comparative study, the relation and seasonal variation of haze and negative emotion of the public were well discussed. According to the study results, there was indeed a correlation between haze and negative emotion of the public, but the strength of this relationship varied under different conditions. The level of air pollution and weather context were both important factors that influence the mental effects of haze, and diverse patterns of negative emotion expression were demonstrated in different seasons of a year. Finally, for the benefit of people&rsquo, s mental health under haze, recommendations were given for haze control from the side of government.

This study aimed to compare the influence between Cimicifuga foetida extract and different hormone therapies on breast pain in early postmenopausal women. A prospective, randomized, controlled clinical trial was conducted among 96 early postmenopausal women. Participants were randomly assigned to three groups: group A received 1 mg/day estradiol valerate plus 4 mg/day medroxyprogesterone acetate on days 19-30; group B received 1 mg/day estradiol valerate plus 100 mg/day micronized progesterone on days 19-30; group C received C. foetida extract, 1talet (contains 33.3 mg extract), t.i.d. Breast pain diary and numerical rating scale was used to access the breast pain. For 6 months' treatment, the total incidence of breast pain in group A and B was significantly higher than that in group C (p .05). The duration (day) of breast pain in each month decreased over time in group A and B while it was continuously low and without significant change in group C (p .05). The intensity of breast pain was mild in most participants and did not differ among three groups (p .05). During treatment of early postmenopausal women with C. foetida extract for 6 months, the incidence and duration of breast pain were lower than upon treatment with E2 plus cyclic MPA or m-P and did not change over time.

The concentrations of polycyclic aromatic hydrocarbons (PAHs) in two 210Pb-dated sediment cores collected from mud deposits along the southeastern coast of the Liaodong Peninsula were investigated to reconstruct the sedimentary records of PAHs and their relationship with anthropogenic and natural activities. The concentrations of 16 PAHs (∑PAHs) were low and remained stable before the year 1820, reflecting an autarkic agricultural civilization. From 1820 to 1900, with the gradual lifting of prohibition, people migrated into Northeast China, resulting in the release of large amounts of ∑PAHs into the environment. At the beginning of the 1900s, the ∑PAH levels in the two cores displayed increasing trends with significant fluctuations, linked to a period of social turbulence with continuous wars in Northeast China. After 1949, vertical ∑PAH trends in the cores predominantly reflected trends in economic development. Based on the different PAH composition trends (2–3-ring and 4–6-ring PAHs), we consider that historical energy usage in Northeast China can be divided into three stages: biomass fuel use dominated before 1920, biomass and fossil fuels co-existed from 1920 to 1980, and fossil fuels dominated after 1980. In addition, this study also demonstrates that the PAH concentrations (2–3-ring PAHs) in these two sediment cores can be used, to a certain extent, to identify anthropogenic fire events.

To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction.Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period.After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) μmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mL•minNiaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).

This study investigated the prevalence of abnormally cleaved embryos and determined which types of abnormally cleaved embryos (1-3c, 2-4c, 3-5c, 4-6c), might be suitable for transfer based on live birth data. One hundred seventy-one women (whose transferred embryos were confirmed to be either fully implanted or fully unimplanted) provided 1256 embryos, which were analyzed. Of these embryos, 320 embryos were transferred, of these transferred embryos, 291 embryos were normal and 29 embryos were abnormal, which five embryos were not analyzed because each one was presented one abnormal cleavage type. These 24 embryos were divided into four groups. Inclusion criteria were as follows: women under 37 years of age undergoing first fresh in vitro fertilization (IVF) treatment with a basal antral follicle count of 5–15, body mass index (BMI) of 18–25 kg/m2, number of retrieved oocytes between 5 and 20, and tubal factors as the cause of infertility. Time-lapse imaging analysis software was used to compare temporal parameters of normal cleavage and abnormal cleavage groups (there were four abnormal groups, based on the prevalence of abnormal cleavage embryos). Cleavage times were analyzed before the abnormal cleavage occurred, and time intervals were analyzed after the abnormal cleavage based upon the types of abnormal cleavage. In addition, the time intervals of t4-t3 and t8-t5 were also analyzed; corresponding time parameters were measured in the normal group as well. Implantation rate, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate were also measured in the normally cleaved and abnormally cleaved embryos. The prevalence of abnormal cleavage was 15.92 % (200/1256). T8-t5 was the most important parameter in the prediction of potential development (production of a live-born baby) of abnormally cleaving embryos. Abnormally cleaving embryos were able to produced live births with T8-t5 the best parameter to predict the developmental potential of abnormally cleaving embryos.

Summary The association between potential long-term effects of previous schistosome infection (PSI) and the development of metabolic syndrome remains unknown. Therefore, we aimed to evaluate the association between them. Participants were from regions which were all reportedly heavily endemic for S. japonicum in China 40 years ago. One thousand five hundred and ninety-seven men were enrolled. Among these, 465 patients with PSI were selected as study subjects and 1132 subjects served as controls. We found PSI significantly correlated with lower prevalences of metabolic syndrome and its components, including central obesity, hypertriglyceridemia and low high-density lipoprotein cholesterol, which indicates that the potential long-term effects of PSI may reduce the risk of metabolic syndrome. However, further studies are needed to investigate the protective immune effects of PSI.

The major purpose of this study was to assess the association between the potential long-term effects of previous schistosome infection and atherogenic dyslipidemia. Among 1597 men aged ⩾45 years who received health examinations and lived in previous schistosomiasis-endemic regions of China, 465 patients with previous schistosome infection were selected as study subjects, and 1132 subjects formed the control group. The risk factors for cardiovascular disease were measured and compared between the previous schistosome infection and control groups. The Atherogenic Index of Plasma, triglycerides, waist circumference and body mass index were significantly lower in the previous schistosome infection group than in the control group (all P values

Background: It is now recognized that Cimicifuga foetida (C. foetida) extract is effective in alleviating menopausal symptoms. But the durations reported were usually short. The aim of this study was to investigate the effects of C. foetida extract therapy and different estrogen and progesterone sequential therapies, on the breasts of early postmenopausal women. Methods: This was a prospective randomized trial. Ninety-six early menopausal women were recruited and randomly assigned into three groups treated with different therapies for 2 years. Patients were given C. foetida extract in Group A, estradiol valerate and medroxyprogesterone acetate in Group B, and estradiol valerate and progesterone in Group C. Ultrasonography was used to monitor changes in breast during treatment. Results: In comparing breast glandular section thickness before and after 1 and 2 years of treatment, no significant difference was observed in Group A (11.97 ± 2.84 mm vs. 12.09 ± 2.58 mm and 12.61 ± 3.73 mm, P > 0.05); in Group B glandular section thickness had increased significantly (10.98 ± 2.34 mm vs. 11.84 ± 2.72 mm and 11.90 ± 3.33 mm, P < 0.05) after treatment, the same as Group C (11.56 ± 3.03 mm vs. 12.5 ± 3.57 mm and 12.22 ± 4.39 mm P < 0.05). In comparing breast duct width before and after 1 and 2 years of treatment, no significant difference was seen in Group A (1.07 ± 0.19 mm vs. 1.02 ± 0.18 mm and 0.98 ± 0.21 mm, P > 0.05); in Group B the duct width had a downward trend after treatment (0.99 ± 0.14 mm vs. 0.96 ± 0.22 mm and 0.90 ± 0.18 mm, P < 0.05), the same as Group C (1.07 ± 0.20 mm vs. 1.02 ± 0.17 mm and 0.91 ± 0.19 mm, P < 0.05). The nodules detected before treatment had disappeared after 1-year of treatment or exhibited no distinct changes in the three groups. However, new breast nodules had appeared after 2 years of treatment: There was one case in Group A, two cases in Group B and four cases in Group C, with breast hyperplasia after the molybdenum target check. Conclusions: In early postmenopausal patients, C. foetida extract therapy and estrogen and progesterone therapy at low doses did not increase the incidence of malignant breast tumors

The aim of this study was to evaluate the efficacy and safety of long-term treatment with Cimicifuga foetida extract in menopausal women.A prospective, randomized, controlled clinical trial was conducted. A total of 96 early postmenopausal women were randomly assigned to three groups: group A received 1 mg estradiol valerate daily plus 4 mg medroxyprogesterone acetate on days 19-30; group B received 1 mg estradiol valerate daily plus 100 mg micronized progesterone on days 19-30; group C received 100 mg C. foetida extract daily. The efficacy was evaluated. Safety parameters were recorded.A total of 81 patients completed the treatment and follow-up visit. The modified Kupperman Menopausal Index scores decreased after 3 months in all groups. No significant changes were observed in the liver, renal function and components of metabolic syndrome in group C (p 0.05). There were no significant differences in the incidences of metabolic syndrome among the three groups (p 0.05). After 24 months, the endometrial thickness increased significantly in group B (p = 0.014), but not in the C. foetida extract group (p 0.05).C. foetida extract is safe and effective for the treatment of menopausal symptoms in postmenopausal women.

To investigate the damage effect of 5-fluorouracil(5-FU) with tumor inhibition concentration on human bone marrow mesenchymal stem cells (hBMSC) and influence of its effect on the hematopoietic cells.The Cell Counting Kit-8 was used for determining the sensitivity of breast cancer cell line MCF-7, colon cancer cell line HCT-116 and HS-5 derived from human bone marrow stronal cell line to the different doses of 5-fluorouracil in vitro. After HS-5 was treated with 5-fluorouracil, crystal violet staining assay was used to count the number of colony forming unit-fibroblast, the distribution of cell cycle was analyzed by flow cytometry (FCM), apoptosis was assessed by Annexin V/PI double-stained method and Hoechest staining; DCFH-DA staining was used to analyse the level of reactive oxygen species (ROS), ELISA and immuofluorescence were used to detect cytokines KL, GM-CSF, RANTS and SDF. The hUCB-MNC was counted by trypan blue staining after co-culture with HS-5, FCM was used to detect the cell cycle distribution, ROS level and the ratio of CD345-Fluorouracil of 12.5 µg/ml-100 µg/ml inhibited the proliferation of MCF-7, HCT-116 and HS-5 cells in dose-dependent and time-dependent manner, among them HS-5 was more sensitive to 5- fluorouracil. After treatment with 5-fluorouracil, the HS-5 cell cycle was blocked. The apoptosis rate and the intracellular ROS level of HS-5 significantly increased. Also HS-5-secreted hematopoietic growth factors decreased and inflammatory chemokines increased. After co-cultured with 5-fluorouracil-treated HS-5, the number of hUCB-MNC and the ratio of CD345-Fluorouracil can result in oxidative damage of bone marrow stromal cells and change of function secreting bioactivators, thus induce oxidative stress in hematopoietic cells to initiate stress-induced premature senescence (SIPS).

Interferon gamma (IFN-γ) is a potent proinflammatory cytokine which plays a pivotal role in the antiviral, antiproliferative, and antitumor activities. A T-to-A transition at the position +874 of human IFN-γ gene (IFNG) has been reported to influence the secretion of IFN-γ and affect cancer susceptibility. However, results from published studies on the association between IFNG +874 T/A polymorphism and cancer risk are inconclusive or even controversial. In order to derive a more precise estimation of the association, a meta-analysis of 38 eligible studies including 5,630 cases and 6,096 controls was conducted with odds ratio (OR) and its corresponding 95 % confidence interval (95 % CI). Overall, no significant association was detected in allelic model (A allele vs. T allele-OR = 0.96, 95 % CI, 0.86-1.08), homozygote comparison (AA vs. TT-OR = 0.97, 95 % CI, 0.79-1.21), heterozygote comparison (AT vs. TT-OR = 1.03, 95 % CI, 0.87-1.23), dominant model (AA + AT vs. TT-OR = 1.00, 95 % CI, 0.87-1.15), nor recessive model (AA vs. AT + TT-OR = 0.93, 95 % CI, 0.78-1.12). Further subgroup analyses based on ethnicity, cancer types, and Hardy-Weinberg equilibrium status failed to demonstrate any significant relationship except in African population under recessive model (AA vs. AT + TT-OR = 0.68, 95 % CI, 0.47-0.97). In conclusion, the current meta-analysis suggested that IFNG +874 T/A polymorphism may not contribute to cancer susceptibility, and further well-designed studies with large sample size are warranted to validate our conclusion.

Background Melanoma is a lethal cancer. NF-κB has been validated as a molecular target for melanoma treatment. Current therapies for melanoma have limitations. Novel targeted therapeutics are needed. Arnicolide D (Ar-D), a sesquiterpene lactone isolated from the dried whole plant of Centipeda minima (L.) A. Br. et Aschers., has been reported to inhibit NF-κB activity in colorectal cancer cells. Purpose To investigate the anti-melanoma effects of Ar-D in vitro and in vivo; and to determine whether Ar-D inhibits the NF-κB pathway in melanoma cells. Methods A B16F10 allograft mouse model and two melanoma cell lines (A375 and B16F10) were used to investigate the anti-melanoma effects of Ar-D in vivo and in vitro. Dacarbazine was used as a positive control. Cell viability was assessed by MTT and crystal violet staining assays. Cell cycle arrest and apoptosis were analyzed by flow cytometry. Protein levels were determined by Immunoblotting. Results In vivo assays showed that the average tumor weight in Ar-D-treated group (4 mg/kg, i.p, 15 days) was reduced by 53.7%, when compared with the control group. In vitro studies demonstrated that Ar-D reduced cell viability, induced G2/M cell cycle arrest and apoptosis, elevated levels of cell cycle regulatory proteins p53 and p21, and lowered levels of G2/M checkpoint proteins Cdc2 and Cyclin B1 in melanoma cells. Mechanistically, Ar-D inhibited the activity of IKKα/β, the degradation of IκBα, and the phosphorylation and expression of NF-κB p65 in melanoma cells. Conclusion Ar-D has anti-melanoma effects, and inhibition of the IKK/IκBα/NF-κB p65 pathway is involved in the effects.

Background Metastasized melanoma is extremely difficult to treat. Activation of C-C chemokine receptor type 7 (CCR7) has been linked to melanoma metastasis. CCR7 can be directly regulated by miR-let-7. We have previously shown that an ethanolic extract of an herbal formula comprising Sophorae Flos and Lonicerae Japonicae Flos (SLE) inhibits melanoma cell migration and invasion. Purpose In this study, we determined whether SLE suppresses melanoma metastasis, and whether regulation of miR-let-7a/f-CCR7 signaling is involved in the effect. Study design and methods Small RNA sequencing was conducted to compare miRNA expression profiles of B16F10 tumors dissected from SLE-treated or untreated mice. Western blot and RT-qPCR analyses were employed to examine protein and miRNA levels, respectively. A B16F10 melanoma lung metastasis mouse model was used to evaluate the effects of SLE on melanoma metastasis. MiR-let-7a/f-knockdown and CCR7-overexpression cell models were used to investigate the involvement of miR-let-7a/f-CCR7 signaling in the anti-metastatic effects of SLE. Results It was found that SLE upregulated levels of miR-let-7a/f in B16F10 melanoma tissues. SLE significantly elevated levels of miR-let-7a/f, lowered the protein level of CCR7, inhibited the phosphorylation of CCR7 downstream molecules p38 and JNK in B16F10 and A375 melanoma cells. SLE inhibited B16F10 melanoma lung metastasis in mice. SLE upregulated levels of miR-let-7a/f, and lowered protein levels of CCR7, MMP-2, MMP-9, phospho-p38 (Thr180/Tyr182) and phospho-JNK (Thr183/Tyr185) in melanoma-invaded lung tissues. Knockdown of miR-let-7a/f diminished the effects of SLE on CCR7 signaling in, and invasion of, melanoma cells. Overexpression of CCR7 lessened the effects of SLE in inhibiting the phosphorylation of p38 and JNK in, and the invasive capability of, melanoma cells. Conclusion We for the first time demonstrated that SLE inhibits melanoma metastasis in mice, and that regulation of the miR-let-7a/f-CCR7 pathway contributes to the anti-metastatic mechanisms of SLE. These findings provide a pharmacological basis for developing SLE as a modern agent for treating metastatic melanoma. Additionally and importantly, this study suggests that regulating the miR-let-7a/f-CCR7 pathway is a novel strategy for controlling melanoma metastasis.

To evaluate the different traits of mesenchymal stem cell (MSC) isolated from osteosarcoma (OS) and normal bone marrow (BM) induced by bone-morphogenetic protein-2 (BMP-2). MSCs from implanted osteosarcoma or femur bone marrow were isolated and cultured. Differentiation potency was verified and phenotypes were evaluated by flow cytometry. Increased or decreased expressions of BMP-2 were delivered by adenovirus and lentivirus vector, respectively. Expressions of VEGF, EMMPRIN, and MMP-9 were examined. Cell cycle, apoptosis, invasiveness, and proliferation assays were performed between the transfected groups and controls. Increased BMP-2 induced over-expression of VEGF, EMMPRIN, and MMP-9 in OS- and BM-MSCs both intra- and extra-cellularly. Decreased BMP-2 expression induced inhibition of the factors. Increased BMP-2 also induced less population of cells at G1 phase, more apoptotic cells, more cells that invade through Transwell membrane, and faster proliferation in OSMSC compared to those in BMMSC. BMP-2 induced higher expression of tumorigenic factors, which could be responsible for promoting the proliferation and aggressiveness of OSMSC over BMMSC.

Background: The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy (IgAN) are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN. Methods: It is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan (80 mg/d) wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo (Group A), 50 mg/d clopidogrel (Group B), 20 mg/d leflunomide (Group C), or 50 mg/d clopidogrel and 20 mg/d leflunomide (Group D). The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry. Results: The effects of telmisartan combined with leflunomide on changes in proteinuria (0.36 [95% confidence interval (CI) 0.18–0.55] g/d, P < 0.001), in serum uric acid (76.96 [95% CI 57.44–96.49] μmol/L, P < 0.001), in serum creatinine (9.49 [95% CI 6.54–12.44] μmol/L, P < 0.001), and in estimated glomerular filtration rate (−6.72 [95% CI −9.46 to −3.98] ml∙min−1∙1.73 m−2, P < 0.001) were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight (P > 0.05). Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed. Conclusions: Telmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients. Trial Registration: chictr.org.cn, ChiCTR-TRC-10000776; http://www.chictr.org.cn/showproj.aspx?proj=8760.

To explore the protective effect of Angelica sinensis polysaccharides(ASP) on subacute renal damages induced by D-galactose in mice and its mechanism. Male C57BL/6J mice were randomly divided into 3 groups, with 10 mice in each group. The D-galactose model group was subcutaneously injected with D-galactose (120 mg x kg(-1)), qd x 42; the ASP + D-galactose model group was intraperitoneally injected with ASP since the 8th day of the replication of the D-galactose model, qd x 35; and the normal control group was subcutaneously injected with saline at the same dose and time. On the 2nd day of after the injection, the peripheral blood was collected to measure the content of BUN, Crea, UA, Cys-C; paraffin sections were made to observe the renal histomorphology by HE staining; senescence-associated β-g-alactosidase (SA-β-Gal) stain was used to observe the relative optical density (ROD) in renal tissues; transmission electron microscopy was assayed to observe the renal ultrastructure; the renal tissue homogenate was prepared to measure the content of SOD, GSH-PX, MDA; the content of AGEs and 8-OH-dG were measured by ELISA. According to the result, compared with the D-galactose model group, the ASP + D-galactose model group showed obviously decreases in the content of BUN, Crea, UA, Cysc, AGES, 8-OH-dG, the number of hardening renal corpuscle, renal capsular space and renal tubular lumen, ROD of SA-β-Gal staining positive kidney cells, mesangial cells, basement membrane thickness, podocyte secondary processes fusion and MDA and increases in the number of normal renal corpuscle, ribosome and rough endoplasmic reticulum in podocytes, the activity of SOD and GSH-PX. In Conclusion, A. sinensis polysaccharides can antagonize kidney subacute damages induced by D-galactose in mice. Its protective mechanism may be correlated with the inhibition of the oxidative stress injury.

Epimutations are errors in the normal process of epigenetic regulation which can result in aberrant transcriptional silencing of a normally active gene or reactivation of a normally silent gene. Epimutations are generally considered to be somatic events and to be confined in affected tissues. However, recent studies of patients with hereditary nonpolyposis colorectal cancer (HNPCC) have showed that allele-specific hypermethylation of CpG islands in the promoter region of the MLH1 gene, one of the causes of the tumor, existed in all the tissues examined. In addition, germ-line epimutations of other tumor suppressor genes (TSGs), such as MSH2 and BRCA1, have also been reported, demonstrating that epimutations might arise in the germ-line (during gametogenesis or early embryonic development). The role of germ-line epimutations might be as important as germ-line mutations in human disease. We reviewed the update on germ-line epimutations of TSGs including the possible mechanisms underlying germ-line epimutations, the possibility of transgenerational inheritance, and their impact on our understanding of human disease.

The role of atherosclerosis-related processes in aortic root dilatation (ARD) has not been fully determined. The present study was to assess the relationship between carotid IMT, carotid plaque, and ARD.Hypertensive men with ARD (n = 30) were compared with hypertensive men without ARD (n = 52) and normal control subjects (n = 29). Two-dimensional echocardiography was used to measure the aortic root at the aortic annulus, the sinus of Valsalva, the sinotubular junction and the proximal part of the ascending aorta. Carotid IMT and carotid plaque were also assessed by ultrasound.The measured mean carotid IMT was significantly increased in patients with ARD (1.37 +/- 0.80 mm) compared to the subjects without ARD (1.06 +/- 0.54 mm) and healthy control subjects (0.84 +/- 0.44 mm) (P0.05). However, no significant differences of the prevalence of carotid plaque were found in the three groups (P0.05). Aortic diameters at all levels except for the diameter of the supra-aortic ridge were significantly related to carotid IMT when the hypertensive population was considered (P0.05). No significant correlation was found between carotid plaque and aortic root dimension (P0.05).This study shows that carotid intima-media thickening, but not carotid atherosclerotic plaque, is positively associated with ARD. Further studies to explore the underlying mechanism are awaited.

SLP-76 is an important member of the SLP-76 family of adapters, and it plays a key role in TCR signaling and T cell function. Partial cDNA sequence of SLP-76 of common carp (Cyprinus carpio L.) was isolated from thymus cDNA library by the method of suppression subtractive hybridization (SSH). Subsequently, the full length cDNA of carp SLP-76 was obtained by means of 3' RACE and 5' RACE, respectively. The full length cDNA of carp SLP-76 was 2007 bp, consisting of a 5'-terminal untranslated region (UTR) of 285 bp, a 3'-terminal UTR of 240 bp, and an open reading frame of 1482 bp. Sequence comparison showed that the deduced amino acid sequence of carp SLP-76 had an overall similarity of 34-73% to that of other species homologues, and it was composed of an NH2-terminal domain, a central proline-rich domain, and a C-terminal SH2 domain. Amino acid sequence analysis indicated the existence of a Gads binding site R-X-X-K, a 10-aa-long sequence which binds to the SH3 domain of LCK in vitro, and three conserved tyrosine-containing sequence in the NH2-terminal domain. Then we used PCR to obtain a genomic DNA which covers the entire coding region of carp SLP-76. In the 9.2k-long genomic sequence, twenty one exons and twenty introns were identified. RT-PCR results showed that carp SLP-76 was expressed predominantly in hematopoietic tissues, and was upregulated in thymus tissue of four-month carp compared to one-year old carp. RT-PCR and virtual northern hybridization results showed that carp SLP-76 was also upregulated in thymus tissue of GH transgenic carp at the age of four-months. These results suggest that the expression level of SLP-76 gene may be related to thymocyte development in teleosts.

Background We investigated whether there had been an improvement in the quality of reporting for randomised controlled trials of acupuncture and moxibustion published in Chinese journals. We compared the compliance rate for the quality of reporting following the publication of both the STRICTA and CONSORT recommendations in China. Methods Four Chinese databases were searched for RCTs of acupuncture from January 1978 through to December 2012. The CONSORT and STRICTA checklists were used to assess the quality of reporting. Data were collected using a standardised form. All included RCTs were divided into three distinct time periods based on the time that CONSORT and STRICTA were introduced in China, respectively. Pearson's χ2 test and/or Fisher's exact test were used to assess differences in reporting among three groups. Principal Findings A total of 1978 RCTs were identified. Although the percentage of all the items has increased over time with the introduction of CONSORT and STRICTA in China, the actual compliance in several important methodological components, including sample size calculation (0% vs. 0% vs. 1.2%, for pre-CONSORT and pre-STRICTA, post-CONSORT but pre-STRICTA, and post-CONSORT and post-STRICTA, respectively), randomisation sequence generation (1.4% vs. 15% vs. 26.3%) and implementation (0% vs. 0% vs. 1.3%), allocation concealment (0% vs. 1.4% vs. 4.9%), and blinding (0% vs. 5.7% vs. 9.1%), remains low. Moreover, no RCTs have reported the setting and context of treatment and no descriptions of the participating acupuncturists have been provided thus far. Conclusions Overall, the quality of the reporting of RCTs of acupuncture and moxibustion published in Chinese journals has improved since CONSORT and STRICTA were introduced in China, though the actual compliance rate of some important items were still low as of 2012. In the future, Chinese journals should enhance the adoption of the CONSORT and STRICTA statement to improve the reporting quality of the RCTs of acupuncture and moxibustion and to ensure the truth and reliability of the conclusions.

To explore the biological mechanisms underlying Angelica sindsis polysaccharide (ASP) -induced aging of human-derived leukemia stem cells (LSCs) in vitro.Acute myelogenous leukemia stem cells were isolated by magnetic activated cell sorting (MACS). The ability of LSC proliferation treated by various concentration of ASP(20-80 mg · L(-1)) in vitro for 48 hours were tested using cell counting Kit-8 ( CCK8) , colony forming were evaluated by methylcellulose CFU assay. The ultra structure changes of AML CD34+ CD38- cells were analyzed by transmission electron microscopy. The aging cells were detected with senescence-β-galactosidase Kit staining. Expression of aging-related p53, p21, p16, Rb mRNA and P16, Rb, CDK4 and Cyclin E protein were detected by quantitative reverse transcription polymerase chain reaction( qRT-PCR) and Western blotting, respectively.The purity of the CD34 + CD38 - cells is (91.15 ± 2.41)% after sorted and showed good morphology. The proliferation of LSC was exhibited significantly concentration-dependent inhibited after exposure to various concentration of ASP. Treated by 40 mg · L(-1) ASP for 48 hours, the percentage of positive cells stained by SA-β-Gal was dramatically increased (P0.01) and the colony-formed ability has been weakened (P0.01). The observation of ultrastructure showed that cell heterochromatin condensation and fragmentation, mitochondrial swelling, lysosomes increased in number. Aging-related p53, p21, p16, Rb and P16, Rb were up-regulated, protein regulatory cell-cycle CDK4 and Cyclin E were down-regulated. ASP may induce the senescence of LSCs effectively in vitro, P16-Rb cell signaling pathway play a significant role in this process.ASP can induce human leukemia stem cell senescence in vitro, the mechanism involved may be related to ASP regulation P16-Rb signaling pathways.

To evaluate the efficacy and safety of Heyan Kuntai Capsule (, HYKT) and hormone therapy (HT) on perimenopausal syndromes (PMSs).From 2005 to 2008, 390 women with PMSs were recruited from 4 clinic centers. The inclusion criteria included ages 40 to 60 years, estradiol (E2) below 30 ng/L, and follicle stimulating hormone (FSH) above 40 IU/L, etc. The patients were randomly assigned to HYKT group or HT group by random number table method, administrated HYKT or conjugated estrogen with/without medroxyprogesterone acetate tablets for 12 months. During treatment, the patients were interviewed quarterly, Kupperman Menopausal Index (KMI) scores, hot flush scores, insomnia scores, Menopause-Specific Quality of Life (MENQOL) scores and adverse effects were used for evaluating drug efficacy and safety respectively. The last interview was made at the end of 12-month treatment RESULTS: After treatment, KMI scores of HYKT group and HT group were both significantly decreased compared with baseline (P0.01) and there was no significant difference between groups (P0.05), except that KMI of HYKT group was higher after 3-month treatment (P0.05). After treatment, hot flush and insomnia scores were both improved significantly in two groups (P0.01); and HT had a better performance than HYKT in improving hot flush (P0.05). MENQOL were significantly improved in both groups after treatment (P0.01); but there was no significant difference between two groups (P0.05). The incidence of adverse event in the HYKT group was much lower than that in the HT group (P0.01).HYKT could effectively relieve PMSs and improve patients quality of life without severe adverse reactions. Although HYKT exerted curative effects more slowly than hormone, it possessed better safety profile than hormone.

To develop a cell-penetrating chimeric apoptotic peptide AVPI-LMWP/DNA co-delivery system for cancer therapy, we prepared the AVPI-LMWP/pTRAIL self-assembled complexes containing a therapeutic combination of peptide drug AVPI and DNA drug TRAIL. The chimeric apoptotic peptide AVPI-LMWP was synthesized using the standard solid-phase synthesis. The cationic AVPI-LMWP could condense pTRAIL by electrostatic interaction. The physical-chemical properties of the AVPI-LMWP/pTRAIL complexes were characterized. The cellular uptake efficiency and the inhibitory activity of the AVPI-LMWP/pTRAIL complexes on tumor cell were also performed. The results showed that the AVPI-LMWP/pTRAIL complexes were successfully prepared by co-incubation. With the increase of mass ratio (AVPI-LMWP/DNA), the particle size was decreased and the zeta potential had few change. Agarose gel electrophoresis showed that AVPI-LMWP could fully bind and condense pTRAIL at a mass ratio above 15:1. Cellular uptake efficiency was improved along with the increased ratio of W(AVPI-LMWP)/WpTRAIL. The in vitro cytotoxicity experiments demonstrated that the AVPI-LMWP/pTRAIL (W:W = 20:1) complexes was significantly more effective than the pTRAIL, AVPI-LMWP alone or LMWP/pTRAIL complexes on inhibition of HeLa cell growth. Our studies indicated that the AVPI-LMWP/pTRAIL co-delivery system could deliver plasmid into HeLa cell and induce tumor cell apoptosis efficiently, which showed its potential in cancer therapy using combination of apoptoic peptide and gene drugs.

The binding of bromsulphalein (BSP) with human serum albumin was investigated at different temperatures, 298 and 308 K, by the fluorescence spectroscopy at pH 7.24. The binding constant was determined by Stern-Volmer equation based on the quenching of the fluorescence HSA in the presence of bromsulphalein. The effect of various metal ions on the binding constants of BSP with HSA was investigated. The thermodynamic parameters were calculated according to the dependence of enthalpy change on the temperature as follows: DeltaH and DeltaS possess small negative (9.3 kJ mol(-1)) and positive values (22.3 J K(-l)mol(-l)), respectively. The experimental results revealed that BSP has a strong ability to quench the intrinsic fluorescence of HSA through a static quenching procedure. The binding constants between BSP to HSA were remarkable and independent on temperature. The binding constants between HSA and BSP decreased in the presence of various ions, commonly decreased by 30-55%. The hydrophobic force played a major role in the interaction of BSP with HSA. All these experimental results and theoretical data clarified that BSP could bind to HSA and be effectively transported and eliminated in body, which could be a useful guideline for further drug design.

The physiological role of microRNAs (miRNAs) in osteoblast differentiation remains elusive. Exosomal miRNAs isolated from human bone marrow-derived mesenchymal stem cells (BMSCs) culture were profiled using miRNA arrays containing probes for 894 human matured miRNAs. Seventy-nine miRNAs (∼8.84%) could be detected in exosomes isolated from BMSC culture supernatants when normalized to endogenous control genes RNU44. Among them, nine exosomal miRNAs were up regulated and 4 miRNAs were under regulated significantly (Relative fold>2, p

The latest findings of our laboratory showed that Angelica sinensis polysaccharide (ASP) showed a definite effect in regulating the aging of hematopoietic stem cells. Leukemia is a type of malignant hematopoietic tumor in hematopoietic stem cells. There have been no relevant reports about ASP's effect in regulating the aging of leukemia cells. In this study, human acute myeloid leukemia (AML) KG1alpha cell lines in logarithmic growth phase were taken as the study object, and were divided into the ASP group, the cytarabine (Ara-C) group, the ASP + Ara-C group and the control group. The groups were respectively treated with different concentration of ASP, Ara-C and ASP + Ara-C for different periods, with the aim to study the effect of ASP combined with Ara-C in regulating the aging of human acute myeloid leukemia KG1alpha cell lines and its relevant mechanism. The results showed that ASP, Ara-C and ASP + Ara-C could obviously inhibit KG1alpha cell proliferation in vitro, block the cells in G0/G1 phase. The cells showed the aging morphological feature. The percentage of positive stained aging cells was dramatically increased, and could significantly up-regulate the expression of aging-related proteins P16 and RB, which were more obvious in the ASP + Ara-C group. In conclusion, the aging mechanism of KG1alpha cell induced by ASP and Ara-C may be related to the regulation of the expression of aging-related proteins, suggesting that the combined administration of ASP and anticancer drugs plays a better role in the treatment of leukemia .

In addition to the typical size, Cryptococcus neoformans can enlarge its size to form titan cells during infection, and its diameter can reach up to 100 μm. Clinical reports about cryptococcal titan cells are rare. Most studies focus on aspects of animal models of infection with titan cells. Herein, we report the clinical and imaging characteristics and histopathologic features of 3 patients with titan cells and 27 patients with pathogens of typical size, and describe the morphological characteristics of titan cells in details. Histologically, 3 patients with titan cells show necrosis, fibrosis and macrophage accumulation. The titan cells appear in necrotic tissue and between macrophages, and have thick wall with unstained halo around them and diameters range from 20 to 80 μm with characteristic of narrow-necked single budding. There are also organisms with typical size. All 27 patients with normal pathogens show epithelioid granulomatous lesions. There is no significantly difference in clinical and imaging feature between the two groups. Cryptococcus neoformans exhibits a striking morphological change for the formation of titan cells during pulmonary infection, which will result in misdiagnosis and under diagnosis. The histopathological changes may be new manifestation, which need to be further confirmed by the study with animal models of infection and the observation of more clinical cases. Careful observation of the tissue sections is necessary.

Leukemia is a type of malignant tumors of hematopoietic system with the abnormal increased immature leukemia cells showing metastasis and invasion ability. Liver is one of the main targets of the leukemia cells spread to, where they may continue to proliferate and differentiate and cause liver function damage, even liver failure. Our previous studies showed that Angelica polysscharides (APS), the main effective components in Angelica sinensis of Chinese traditional medicine, was able to inhibit the proliferation and induced differentiation of the leukemia cells, however, its effect on the liver during the treatment remains elucidated. In the present study, the human leukemia NOD/SCID mouse model were established by implantation human leukemia K562 cells line, then the leukemia mouse were treated with APS, Ara-c or APS + Ara-c respectively by peritoneal injection for 14 days, to explore the effect and mechanism of the chemicals on the mouse liver. Compared to the human leukemia NOD/SCID mouse model group with the treatments of APS, Ara-c and APS + Ara-c, We found that severe liver damage and pathological changes of the liver were able to alleviate: First, the number of white blood cells in the peripheral blood was significantly lower and with less transplanted K562 leukemia cells; Second, liver function damage was alleviated as liver function tests showed that alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBiL) were significantly reduced, while the albumin (Alb) was notably increased; Third, liver antioxidant ability was improved as the activities of the antioxidant enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were significantly increased, and the contents of GSH and malonaldehyde (MDA) were decreased significantly in the liver; Fourth, the inflammation of the liver was relieved as the level of IL-1beta and IL-6, the inflammatory cytokines, were decreased significantly in the liver. Fifth, liver index was increased as the pathological observation showed that leukemia cells with diffused infiltration into the liver lobules were significantly reduced and with a remarkable increase of apoptotic positive cell rate by TUNEL test. Furthermore, the APS + Ara-c combined administration showed an even more significant positive effect. In conclusion, the APS, Ara-c therapy reduced the accumulation of leukemia cells within the liver, reduced the liver function damage and levels of inflammatory factors, improved antioxidant capacity of the liver tissue and thus alleviate the pathological changes of the liver. Moreover, the APS + Ara-c combination therapy may have an additive effect.

To explore whether the angiotensin I -converting enzyme (ACE) I/D (insertion/ deletion) polymorphism is associated with the susceptibility to high altitude pulmonary edema (HAPE) in the Han Chinese.One hundred and forty-seven HAPE-p (HAPE patients) and 193 HAPE-r (HAPE resistants) were enrolled from the Yushu earthquake reconstruction workers in Qinghai province where the altitude is over 3 500 m above sea level. Blood samples were collected from each of the HAPE-p and HAPE-r groups. Information about physiological phenotypes was obtained via fieldwork investigation. The ACE-I/D polymorphism in HAPE-p and HAPE-r was detected by polymerase chain reaction (PCR).The SaO2 was significantly lower while HR was significantly higher in HAPE-p group than those in HAPE-r group. The genotype frequencies of ACE-I/D for II, ID, DD in HAPE-r and HAPE-p groups were 0.430, 0.446, 0.124 and 0.435, 0.469, 0.095, respectively, the allelic frequencies of I and D were 0.650, 0.350 and 0.670, 0.330, respectively. The OR of ID, DD and D alleles relative to II for HAPE was 0.961 (0.610-1.514), 1.322 (0.634-2.758) and 1.080 (0.783-1.489). There was no significant difference of the genotypic and the allelic frequencies in ACE-I/D polymorphism between HAPE-p and HAPE-r groups.There is no relation between ACE-I/D polymorphism and HAPE in the Han Chinese.