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Background. Complex carcinogenic mechanisms and the existence of tumour heterogeneity in multiple myeloma (MM) prevent the most commonly used staging system from effectively interpreting the prognosis of patients. Since the microenvironment plays an important role in driving tumour development and MM occurs most often in middle-aged and elderly patients, we hypothesize that ageing of bone marrow mesenchymal stem cells (BM-MSCs) may be associated with the progression of MM. Methods. In this study, we collected the transcriptome data on MM from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Differentially expressed genes in both senescent MSCs and MM tumour cells were considered relevant damaged genes. GO and KEGG analyses were applied for functional evaluation. A PPI network was constructed to identify hub genes. Subsequently, we studied the damaged genes that affected the prognosis of MM. Least absolute shrinkage and selection operator (lasso) regression was used to identify the most important features, and a risk model was created. The reliability of the risk model was evaluated with the other 3 GEO validation cohorts. In addition, ROC analysis was used to evaluate the novel risk model. An analysis of immune checkpoint-related genes, tumour immune dysfunction and exclusion (TIDE), and immunophenotypic scoring (IPS) were performed to assess the immune status of risk groups. pRRophetic was utilized to predict the sensitivity to administration of chemotherapeutic agents. Results. We identified that MAPK, PI3K, and p53 signalling pathways were activated in both senescent MSCs and tumour cells, and we also located hub genes. In addition, we constructed a 14-gene prognostic risk model, which was analysed with the ROC and validated in different datasets. Further analysis revealed significant differences in predicted risk values across the International Staging System (ISS) stage, sex, and 1q21 copy number. A high-risk group with higher immunogenicity was predicted to have low proteasome inhibitor sensitivity and respond poorly to immunotherapy. Lipid metabolism pathways were found to be significantly different between high-risk and low-risk groups. A nomogram was created by combining clinical data, and the optimization model was further improved. Finally, real-time qPCR was used to validate two bortezomib-resistant myeloma cell lines, and the test confirmed that 10 genes were detected to be expressed in resistant cell lines with the same trend as in the high-risk cohort compared to nonresistant cells. Conclusion. Fourteen genes related to ageing in BM-MSCs were associated with the prognosis of MM, and by combining this genotypic information with clinical factors, a promising clinical prognostic model was established.

To evaluate the clinical characteristics, treatment and prognosis of systemic anaplastic large cell lymphoma(sALCL).The clinical data of 90 cases with sALCL treated in the Department of Hematology of the Affiliated Xijing Hospital of Air Force Medical University from November 2018 to October 2021 were retrospectively analyzed. The clinical features, treatment and prognosis were summarized and the prognostic factors were investigated.There were 58 males and 32 females, with a median age of 32 (12-73) years old. 69 (76.7%) patients had Ann Arbor stage Ⅲ-Ⅳ disease and half of the patients had extranodal infiltration. The median age was 27(12-72) years of the 60 ALKsALCL mainly occurs in males and most patients were in advanced stage. Half of the patients had extranodal involvement. The CR rate after first-line chemotherapy was 568%, and IPI score≥3 was a significant prognostic factor for CR. No achievement of CR after first-line therapy is poorly prognostic for PFS and OS.系统性间变大细胞淋巴瘤患者的临床特点及预后分析.评价系统性间变大细胞淋巴瘤（sALCL）患者的临床特征、治疗及预后.回顾性分析2018年11月至2021年10月空军军医大学西京医院血液内科收治的90例sALCL患者的临床资料，总结其临床特点、治疗及预后，并探讨预后影响因素.90例sALCL患者中男性58例，女性32例，中位年龄32（12－73）岁。69例（76.7%）患者发病时Ann Arbor 分期为Ⅲ－Ⅳ期，半数患者有结外病变。ALKsALCL以男性居多，诊断时多处于进展期，50%患者合并结外病变。一线化疗后CR率为56.8%，IPI≥3分是一线化疗后CR的不良影响因素。一线化疗后未达CR是PFS及OS 的不良预后因素.

Background. Extramedullary disease (EMD), an infrequent manifestation of multiple myeloma (MM), can present at diagnosis or develop during the disease course. EMD can be clinically divided into bone-related EMD (EMD-B) and soft tissue-related EMD (EMD-S). The purpose of our study is to investigate the clinical characteristics, survival outcomes, and prognostic factors of MM patients with EMD. Methods. A total of 155 MM patients with EMD were ultimately enrolled in our study by retrieving the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan–Meier survival curves and log-rank test for overall survival (OS) and myeloma-specific survival (MSS) were conducted to compare each potential variable. Variables with a p value 1 representing adverse prognostic factors. Results. The median age at diagnosis was 63 years old. EMD-B occurred in 99 patients (63.90%), while EMD-S occurred in 56 cases (36.10%). Patients with EMD-S had a significant survival disadvantage in MSS (HR = 1.844, 95% CI 1.117–3.042, p = 0.017) and OS (HR = 1.853, 95% CI 1.166–2.942, p = 0.009) compared to those with EMD-B. Patients with EMD interval ≤24 months were at higher risk of death than those with EMD at diagnosis in MSS (HR = 1.885, 95% CI 1.175–3.346, p = 0.042) and in OS (HR = 1.33, 95% CI 1.119–2.529, p = 0.036). Patients with EMD interval >24 months were at a lower risk of death as opposed to those with EMD at diagnosis. Conclusion. Age at MM diagnosis, site of EMD, and time interval from diagnosis to EMD occurrence were independent prognostic factors in MM patients with EMD. EMD-B bore a better prognosis than EMD-S.

IntroductionPlasmablastic lymphoma(PBL)，an extremely rare subtype of B-cell non-Hodgkin lymphoma, is characterized by aggressiveness, rapid progression and bleak prognosis. Neither standardized regimen nor consensus for PBL treatment has been established.Material and methodsWe retrospectively analyzed the clinicopathologic characteristics, therapeutic modalities and survival outcomes of 418 patients registered in the Surveillance, Epidemiology, and End Results (SEER) database from 2008 to 2016 and 21 (19 treated) patients in our institution. Kaplan-Meier survival curves and log-rank test for overall survival and disease-specific survival were performed to compare each variable. Variables with statistical significance in the univariate Cox regression were incorporated into the multivariate model to determine the independent prognostic factors.ResultsIn patient cohort from SEER, PBL has a striking male predilection. The median OS for all PBL patients was 17 months. The 1-year,3-year and 5-year OS rate were 54.4%, 40.4% and 37.2% respectively.Chemotherapy alone or chemotherapy combined with radiotherapy could significantly reduce the risk of death and extend the patients’ survival, yielding HR of 0.209(95%CI 0.152-0.288) and 0.187(95%CI 0.089-0.394), respectively. Radiation alone seemed useless. All patients from our institution were HIV-negative. The main therapeutic regimens were CHOP or CHOPE, DA-EPOCH, DHAP and ESHAP. Complete response was achieved in only 3 patients, while partial response in 10 patients. The median OS was 7 months. Fourteen patients later died of the disease progression.ConclusionsPrevious malignancy history, Ann Arbor stage and therapeutic modality were independent prognostic factors. Bortezomib combined with DA-EPOCH may serve as an effective regimen for PBL. The optimal therapeutic modality necessitates further exploration.

Introduction: Plasmablastic lymphoma(PBL)，an extremely rare subtype of B-cell non-Hodgkin lymphoma(NHL), is characterized by aggressiveness, rapid progression and bleak prognosis. Neither standardized regimen nor consensus for PBL treatment has been established.Methods: We retrospectively analyzed the clinicopathologic characteristics, therapeutic modalities and survival outcomes of 418 patients registered in the Surveillance, Epidemiology, and End Results (SEER) database from 2008 to 2016 and 21 (19 treated) patients in our institution. Kaplan-Meier survival curves and log-rank test for overall survival (OS) and cancer-specific survival (CSS) were performed to compare each variable. Variables with statistical significance in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors.Results: In patient cohort from the SEER, PBL has a striking male predilection. The median OS for all PBL patients was 17 months. The 1-year,3-year and 5-year OS rate were 54.4%, 40.4% and 37.2% respectively. Patients who suffered from previous malignancy had a significant survival disadvantage compared to those without previous cancer. Patients with higher Ann Arbor stage at diagnosis were at higher risk of death than those with lower stage. Chemotherapy alone or chemotherapy combined with radiotherapy could significantly reduce the risk of death and extend the patients’ survival, yielding HR of 0.209(95%CI 0.152-0.288) and 0.187(95%CI 0.089-0.394), respectively. Radiation alone seemed useless. All patients from our institution were HIV-negative. The main therapeutic regimens were CHOP or CHOPE, DA-EPOCH, DHAP and ESHAP. Complete response (CR) was achieved in only 3 patients, while partial response (PR) in 10 patients. The median OS was 7 months. Fourteen patients later died of the disease progression.Conclusions: Previous malignancy history, Ann Arbor stage and therapeutic modality were independent prognostic factors. Bortezomib combined with DA-EPOCH may serve as an effective regimen for PBL. The optimal therapeutic modality necessitates further exploration.

IntroductionAutophagy functions as a prosurvival mechanism in multiple myeloma (MM).The objective of this research was to establish an autophagy-related gene (ARG) signature for predicting the survival outcomes of MM patients with TP53 mutations.Material and methodsInformation about MM patients with TP53 mutations was downloaded from Gene Expression Omnibus (GEO) database. Cox proportional hazard regression was employed to determine the independent prognostic ARG and construct a risk signature. Time-dependent receiver-operating characteristic (t ROC) curve was used to explore the predictive accuracy of the prognostic model. A nomogram was constructed to give a more precise prediction of the probability of 5-year, 8-year and 10-year overall survival (OS). In addition, we utilized the CIBERSORT algorithm to explore the distribution difference of 22 immune-infiltrating cells.ResultsThree differentially expressed ARGs (CASP8, MAPK8, RB1CC1) were finally incorporated to construct the risk model. Area under the curve (AUC) of corresponding tROC curve for 5-year,8-year and 10-year OS were 0.735, 0.686 and 0.662, respectively. MM patients were categorized into high and low-risk group in accordance with the median threshold value (-1.724549). ARG-based risk score model was an independent prognostic element correlated with OS, giving an hazard ratio (HR) of 3.29 (95%CI 2.35-4.60, PConclusionsWe established a three-ARGs risk signature which manifested an independent prognostic factor. The nomogram was testified to perform well in forecasting the long-term survival of TP53-mutated MM patients.

Background To evaluate the efficacy and safety of rituximab-based combination therapy for Waldenstrom macroglobulinemia (WM), we conducted this meta-analysis by pooling the rates of overall response, major response, complete response, and grade ≥3 hematological adverse events. Methods and materials We searched for relevant studies in the databases of PubMed, Web of Science, Embase, and the Cochrane Library. The qualitative assessment of all the included articles was conducted with reference to the Newcastle-Ottawa Scale. A random-effects model was selected to perform all pooled analyses. Results We identified altogether 22 studies with a total of 806 symptomatic WM patients enrolled. The pooled analysis indicated that the rituximab-based combination therapy achieved an overall response rate (ORR) of 84% (95% CI: 81%-87%), a major response rate (MRR) of 71% (95% CI: 66%-75%), and a complete response rate (CRR) of 7% (95% CI: 5%-10%). Rituximab plus conventional alkylating agents-containing chemotherapy (subgroup A) yielded an ORR of 86% (95% CI: 81%-89%), an MRR of 74% (95% CI: 69%-79%), and a CRR of 8% (95% CI: 4%-14%). Rituximab plus purine analog (subgroup B) resulted in an ORR of 85% (95% CI: 79%-89%), an MRR of 74% (95% CI: 66%-81%), and a CRR of 9% (95% CI: 4%-15%). Rituximab plus proteasome inhibitor (subgroup C) resulted in an ORR of 86% (95% CI: 81%-90%), an MRR of 68% (95% CI: 58%-77%), and a CRR of 7% (95% CI: 3%-11%). Rituximab plus immunomodulatory drug (subgroup D) attained relatively lower response rates, with an ORR of 67% (95% CI: 51%-81%), an MRR of 56% (95% CI: 27%-83%), and a CRR of 5% (95% CI: 1%-12%). Common grade ≥3 hematological adverse events consisted of neutropenia (33%, 95% CI: 17%-52%), thrombocytopenia (7%, 95% CI: 3%-11%), and anemia (5%, 95% CI: 3%-9%). Conclusion Rituximab in combination with an alkylating agent, purine analog, or proteasome inhibitor is highly effective with tolerable hematological toxicities for WM.

Invasive fungal infections especially in immunocompromised patients represent a dominating cause of mortality. The most commonly used antifungal agents can be divided into three broad categories, including triazoles, echinocandins and polyenes. Antifungal resistance is on the increase, posing a growing threat to the stewardship of immunocompromised patients with fungal infections. The paucity of currently available antifungals leads to the rapid emergence of drug resistance and thus aggravates the refractoriness of invasive fungal infections. Therefore, deep exploration into mechanisms of drug resistance and search for new antifungal targets are required. This review highlights the therapeutic strategies targeting Hsp90, calcineurin, trehalose biosynthesis and sphingolipids biosynthesis, in an attempt to provide clinical evidence for overcoming drug resistance and to form the rationale for combination therapy of conventional antifungals and agents with novel mechanisms of action. What's more, this review also gives a concise introduction of three new-fashioned antifungals, including carboxymethyl chitosan, silver nanoparticles and chromogranin A-N46.

Galectin-3, a microglia/macrophage-derived inflammatory mediator, plays a role in the stroke progression. In this single-center prospective study, we included 288 consecutive patients with a first-ever acute ischemic stroke to assess the association between galectin-3 serum level and clinical severity at admission and outcome at discharge by univariate and multivariate logistic regression. The results were presented as odds ratios (OR) and 95% confidence intervals (CI). Patients with high severity and poor outcomes had higher serum levels of galectin-3 (P

Background: Multiple myeloma (MM) is the second most common hematological neoplasm. Wide administration of bortezomib significantly improves the survival of MM patients compared with conventional chemotherapy. Bromodomain-containing protein 4 (BRD4) inhibitors also have been demonstrated to retard cell proliferation and induce cellular apoptosis in various cancers. However, it is unclear whether the BRD4 inhibitor nitroxoline plus bortezomib has a synergistic anti-tumor effect on MM. Methods: Cell viability was determined via 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle and cell apoptosis were assessed via flow cytometry. Protein expression levels were determined via western blotting. The expression of apoptosis-related proteins in xenograft tissue were detected by means of immunohistochemistry. Results: Treatment with nitroxoline or bortezomib suppressed cell proliferation, and caused G0/G1 phase arrest and apoptosis in H929 and RPMI8226 cells. Furthermore, nitroxoline intensified the retardation of cell proliferation, as well as further enhanced the G0/G1 phase arrest and apoptosis induced by bortezomib in H929 and RPMI8226 cells. The western blot analysis revealed that nitroxoline or bortezomib treatment markedly diminished the levels of Bcl-2 and cyclin D1, and increased the levels of p21, Bax, cleaved PARP and cleaved caspase-3. Combination of these two agents was observed to result in further marked changes on these levels compared with nitroxoline or bortezomib treatment alone. What is more, in the xenograft tumor model, combinative treatment markedly inhibited tumor growth compared with the single drug treatment. Conclusion: Combination of bortezomib with nitroxoline has a synergistic anti-tumor activity in MM cells and may be a novel treatment method for MM.

Objective To assess the effects of Jianpi Shengxue Granule (JSG) on the fertility and early embryo development in rats. Methods Totally 176 SD rats were stratified by sex, and divided into 4 groups, i.e., the control group, low, medium, high dose JSG treatment groups. Rats in the 3 JSG treatment groups were administered with JSG at 0, 1. 16, 3. 48, 5. 80 g/kg per day by gastrogavage, re- spectively. After 2 weeks of administration for females and 4 weeks of administration for males, males and females were caged in the ratio of 1:1. Females were administered to the gestation day 7. Males were administered for 59 -63 days until the day before anatomy. All parental generations were anatomized to observe signs and morphologies. Pathological examination was performed. General toxicity was detected. The testis and epididymis were weighed. Spermatozoa number was counted from epididymis, and repro- duction toxicity of sperm motility was checked. The numbers of corpus luteum, live fetus, dead fetus, and absorbed fetus were counted. The implantation number was calculated to observe early embryo de- velopment toxicity. Results (1) General toxicity: The body weight growth slowed down in male rats of the high dose JSG treatment group. No abnormality was found in low and medium dose JSG treatment groups. (2)Fertility toxicity: There was no obvious toxic effect on testis, epididymis, and spermatozoa number from epididymis sperm in all JSG treatment groups. (3) Early embryo development toxicity: No significant effect on the formation of early embryos was found in all JSG treatment groups. Conclusions Certain gastrointestinal toxicity of JSG might exist to some extent. The dose for non-adverse effect of JSG on fertility and early embryo development was 3. 38 g/kg per day. No obvious fertility or early embryo development toxicity occurred in each JSG treatment group.

Background: Multiple myeloma (MM) is the second most common hematological neoplasm. Wide administration of bortezomib significantly improves the survival of MM patients compared with conventional chemotherapy. Bromodomain-containing protein 4 (BRD4) inhibitors also have been demonstrated to retard cell proliferation and induce cellular apoptosis in various cancers. However, it is unclear whether the BRD4 inhibitor nitroxoline plus bortezomib has a synergistic anti-tumor effect on MM. Methods: Cell viability was determined via 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle and cell apoptosis were assessed via flow cytometry. Protein expression levels were determined via western blotting. The expression of apoptosis-related proteins in xenograft tissue were detected by means of immunohistochemistry. Results: Treatment with nitroxoline or bortezomib suppressed cell proliferation, and caused G0/G1 phase arrest and apoptosis in H929 and RPMI8226 cells. Furthermore, nitroxoline intensified the retardation of cell proliferation, as well as further enhanced the G0/G1 phase arrest and apoptosis induced by bortezomib in H929 and RPMI8226 cells. The western blot analysis revealed that nitroxoline or bortezomib treatment markedly diminished the levels of Bcl-2 and cyclin D1, and increased the levels of p21, Bax, cleaved PARP and cleaved caspase-3. Combination of these two agents was observed to result in further marked changes on these levels compared with nitroxoline or bortezomib treatment alone. What is more, in the xenograft tumor model, combinative treatment markedly inhibited tumor growth compared with the single drug treatment. Conclusion: Combination of bortezomib with nitroxoline has a synergistic anti-tumor activity in MM cells and may be a novel treatment method for MM.

Background Accumulating evidence has indicated that the dysregulation of immunological environment has an important role in the pathogenesis of myelodysplastic syndromes (MDS). The previous studies about the levels of the inflammatory cytokines in MDS, such as TNF-α, IFN-γ, IL-6, IL-8, and IL-17, have yielded controversial results. Thus, we performed a meta-analysis to assess the levels of these inflammatory cytokines in MDS. Methods A systematic search in PubMed, MEDLINE, Cochrane Library, Web of Science, CNKI, and CBM was conducted to find eligible studies. Meta-analyses were performed using STATA 12.0 for Windows. Heterogeneity between included studies was assessed by I test. We chose SMD as the summary statistic. Results A total of 697 individuals from 11 studies were included in this study. Our results suggest the levels of TNF-α, IL-6, IL-8 were significantly higher in MDS patients compared with controls, SMD and 95%CI was 1.48 (0.60, 2.36), 0.71 (0.16, 1.25) and 0.69 (0.28, 1.09), respectively. Moreover, the levels of IL-17 have decreased in the high-risk MDS, the SMD and 95% CI was 2.96 (0.78, 5.15). Conclusion A close association between immunological microenvironment disorders and the pathogenesis of MDS was revealed in this meta-analysis. More importantly, the profiles of inflammatory cytokines appear to change along the progression of the disease.

With the constant development of wireless sensor networks technology, the expanding application scope and the increasing processing power of sensor nodes, there are more and more data collected and processed through the sensor, thus ensuring the security of information transmission between nodes is in urgent needs. The secure application of wireless sensor networks has become a hot technology. This paper mainly expounds the key management schemes of wireless sensor networks, and analyzes the mainstream key management schemes.

Insufficience of osteogenesis and antimicrobial effect have been still impacted the long term clinical success rate of dental implants. A nanostructured titanium surface prepared by hydrothermal treatment with H2O2 was evaluated on its osteoblastic viability and antibacterial effect. Samples were divided into 2 groups: untreated pure titanium surface (Ti) and a nanostructured titanium surface (NT). The antibacterial activities against S.mutans and C.albicans were measured by film applicator coating assay, as well as the live/dead bacteria stain. The osteoblastic viability was investigated by SEM and MTT assay. Results showed that the active microbia on NT was reduced at 24h (P

To observe the toxicity of fangyouling after one month' s transdermal administration in rabbits and evaluate its security.Forty rabbits were randomly divided into 4 groups including a control group and low, middle and high dose groups of fangyouling. The rabbits in the control group were administered with sunflower oil, and the other rabbits were administrated dermally with fangyouling of 50,300 and 2,000 mg/kg respectively once a day for 4 weeks. The general condition, the skin irritation reaction, body weight, food consumption, hematology, blood biochemistry, organ coefficients and histopathological changes of all the rabbits were observed.There was no obvious effect on the general condition in all the rabbits. However, the mild skin irritation was observed in 2 rabbits of the middle dose group and 4 rabbits of the high-dose group. The decreases of body weight and food consumption were noted in the high dose group. No changes were detected of hematology, blood biochemistry or viscera pathological at all dose levels.The dose of non-toxic response of fangyouling is 50 mg/kg at this study condition.

To observe the effect of low-frequency electroacupuncture (EA) treatment on oxidative stress and metabolism disorder in polycystic ovary syndrome (PCOS) rats, so as to study its underlying mechanisms in improving PCOS.Thirty female SD rats were randomized into control group, model group and EA group (n = 10 in each group). The PCOS model was established by subcutaneous injection of testosterone propionate (1 mg/100 g, 10 mg/mL) for 8 weeks. EA (2 Hz) was applied to "Zhongwan" (CV 12) , "Guanyuan" (CV 4) and bilateral "Sanyinjiao" (SP 6) or "Housanli" (ST 36) for 30 min, once daily (except weekends) for 5 weeks. Serum testosterone (T) , sex hormone-binding globulin (SHBG) and fasting serum insulin (FINS) contents were detected by ELISA, serum malondialdehyde (MDA) and superoxide dismutase (SOD) levels were assayed by thiobarbituric acid (TBA) and xanthine oxidation (XTO) methods, respectively, and fasting blood glucose (FBG) was determined by roche glucose meter. In addition, homeostasis model assessment for insulin resistance (HOMA-IR) and modified B cell function index (MBCI) were calculated.Compared with the control group, serum T, FBG, FINS, HOMA-IR, and serum MDA levels were significantly increased in the model group (P0.01), while serum SHBG, MBCI and SOD levels were considerably decreased in the model group (P0.01). Following EA treatment, all the increased serum T, FBG, FINS, HOMA-IR, and serum MDA levels, and the decreased serum SHBG, MBCI and SOD levels were reversed obviously (P0.05, P0.01).EA treatment may normalize insulin sensitivity, ameliorate insulin resistance and hyperinsulinemia in PCOS rats, probably by regulating the function of pancreatic islets β cell and by reducing oxidative stress and free androgen.

To study the effect of hypergravity exposure after 30 days of simulated weightlessness on the expression of chemokine CCL20 and its receptor CCR6 in gingival tissue of rhesus macaque.Twenty-three male rhesus monkeys were randomly divided into 4 groups, namely control group (A,n=3), weightlessness group (B,n=3), hypergravity group (C,n=3) and hypergravity exposure after 30 days of simulated weightlessness group (D, n=14). Group D was further divided into 4 subgroups according to the values of overload as: +11 Gx /270 s group (D1, n=3), +13 Gx /230 s group (D2,n=4), +15 Gx/200 s group (D3,n=4) and +13 Gx /230 s with 9 days of recovery group (D4, n=3). Histopathological changes of gingival tissues were observed by hematoxylin-eosin staining and the expressions of CCL20 and CCR6 were detected by immunohistochemistry (IHC) and quantitative real-time PCR (Q-PCR). SPSS 17.0 software package was used for statistical analysis.Histological observation showed that no significant histopathological change was found in the gingival tissues in all experimental groups. However, there were more infiltrated lymphocytes and neutrophils in the experimental groups. Normal gingival epithelial cells were hardly stained by anti-CCL20 but weakly stained by anti-CCR6. In the experimental groups, CCL20 could be detected in the basal layer of the gingival epithelial tissue, and CCR6 could be detected in the spinous layer and the basal layer of the gingival epithelium. The CCL20 and CCR6 expression in the gingival tissues of each experimental group were significantly higher than those of the control group, not only at the protein level but at the mRNA level (P0.05) except the CCL20 expression in the weightlessness group.Hypergravity exposure after 30 days of simulated weightlessness will not lead to significant pathological changes in gingival tissues, but can induce the expression of chemokine CCL20 and its receptor CCR6 in gingival tissue.

To observe the effect of Yangjing Zhongyu Decoction (YZD) on mRNA and protein expression of PCNA, StAR, and FSHR in ovarian granulose cells (GCs) cultured by excess androgen.Ovarian GCs from porcine follicles were isolated and cultured in vitro. Follicular stimulating hormone (FSH) or YZD was added in the GCs treated by excess testosterone propionate. Totally 48 h later mRNA and protein expression of PCNA, StAR, and FSHR were detected by RT-PCR and Western blot.Excess androgen inhibited mRNA and protein expression of PCNA, StAR, and FSHR of GCs. FSH and YZD could antagonize inhibition of excess androgens, and promote mRNA and protein expression of PCNA, StAR, and FSHR in GCs.YZD could antagonize the inhibition of excess androgen on mRNA and protein expression of PCNA, StAR and FSHR in GCs. Thus, we inferred that YZD could improve the follicle dysplasia by promoting mRNA and protein expression of PCNA, StAR and FSHR in GCs.

Previous studies have shown that hepatitis B core antibody (anti-HBc) levels vary during different phases of disease in treatment-naïve chronic hepatitis B (CHB) patients and can be used as a predictor of both interferon-α and nucleoside analogue therapy response. However, there is no information on the association between the quantitative serum anti-HBc (qAnti-HBc) level and liver inflammation in CHB patients. Therefore, we investigated these relationships in a large cohort of treatment-naïve CHB patients. A total of 624 treatment-naïve CHB patients were included in the study. The serum qAnti-HBc level was moderately correlated with ALT and AST levels (P

To observe the therapeutic effect of acupoint sticking of Wuzhuyu (Evodia Rutaecarpa) for treatment of bradycardia.Sixty cases were randomly divided into an observation group and a control group, 30 cases in each group. The observation group was treated with acupoint sticking of Wuzhugu (Evodia Rutaecarpa) at Neiguan (PC 6) and Xinshu (BL 15) once each day. The control group was treated with oral administration of Xinbao pills, 3 pills each time, thrice each day. The therapeutic effects and changes of 24 hours' holter were observed after 4 weeks.After treatment, 24 hours' average heart rate was significantly improved in the two groups, with significant differences as compared with those before treatment (both P0.01) and with no significant difference between the two groups (P0.05). The total effective rate was 86.7% (26/30) in the observation group and 83.3% (25/30) in the control group, their therapeutic effect being similar.Acupoint sticking of Wuzhugu (Evodia Rutaecarpa) can significantly raise the levels of 24 hours' average heart rate in the patients of bradycardia. This therapy and Xinbao pills have similar therapeutic effect on the improvement of clinical symptom and heart rate levels.

To establish the diagnostic model for endometriosis by screening the plasma biomarkers of endometriosis using surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS)coupled with bioinformatics.Plasma samples from 36 patients with endometriosis (endometriosis group) matched with 35 patients with infertility or benign ovarian tumors (control group) before laparoscopy were collected at Peking Union Medical College Hospital from January to October 2007. Plasma protein profiling were detected using SELDI-TOF-MS and protein chip and peak intensities were compared between the two groups. Biomarker Discovery Software was used for data analysis and model was build by classification and regression tree software (CART), sensitivity and specificity of the diagnostic model were verified.There were 14 protein peaks abnormally expressed in endometriosis group compared with those of control group (P0.01). The diagnostic model composed of three protein peaks with the molecular weight of 3,956,000, 11,710,000 and 6,986,000 showed a sensitivity of 92% and specificity of 83%. In the blind test the model showed a sensitivity of 88% and specificity of 80%.SELDI-TOF-MS is a new approach for screening markers of endometriosis. Its clinical value deserves further investigation.

To develop the rationales for ovarian cancer-specific protein profiles in serum and to analyze the protein profiles of multidrug resistance P-glucoprotein (MDR1) and multidrug resistance-associated protein (MRP) positive and negative expression sets for a rapid and sensitive serum protein pattern.Serum protein profiles from 36 epithelial ovarian cancer cases were compared with 30 healthy controls using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (DELDI-TOF-MS). Blinded test was conducted subsequently for identification of the protein pattern. Expression of MDR and MRP were detected in set of training cases by immunohistochemistry. The spectra were analyzed statistically between positive and negative groups.Twenty-nine peaks were significantly different between ovarian cancer and healthy controls (P0.01, 15 peaks up-regulated and 14 down-regulated). A set of three peaks, at 5 486, 6 463 and 8 575 m/z respectively, were selected from 29 sense peaks as an ovarian cancer biomarker. The sensitivity was 100% and specificity 93.33%. Identification by blinded validation indicated a positive predictive value of 90%. MDR1 expression in ovarian cancer was 69.4 %. Twenty peaks were significantly different between positive and negative sets (P0.01). MRP expression in ovarian cancer was 63.8%. But one peak was detected (P0.01).It was an ideal pattern for employing the SELDI mass spectrum approach to diagnose ovarian cancer and select the multidrug resistance cases. Serum biomarkers for detecting drug resistance in ovarian cancer can be established on the basis of MDR1 immunohistochemistry.

To search the tissue biomarker in mycosis fungoides (MF) patients by surface enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS).Skin specimens were collected from 12 MF patients and 15 normal controls to prepare solution of protein. CM10 Proteinchip was used to detect the biomarkers for MF. Differentially expressed protein was identified by immuno capturing.The expression intensity levels of 24 proteins were different between the MF patients and controls. By searching in SWISS-PRO database and literature, the 3498 and 10 837 peaks were found to accord with HNP3 and S100A8 proteins respectively. By immuno capturing, 10 837 could be identified as S100A8 with a special antibody against S100A8.A quick, easy, and high throughout proteome analytic method, SELDI-TOF-MS can identify the differential expressed proteins from MF tissue, thus offering a unique platform for biomarker detection of MF.

To screen serum biomarkers in patients with mycosis fungoides (MF) using surface-enhanced laser desorption and ionization with time-of-flight detection mass spectrometry (SELDI-TOF-MS) technique.Serum was analyzed from 14 patients with MF and 17 controls using CM10 Protein-chip to capture serum proteins, followed by Biomarker Wizard software analysis.In all specimens, about 131 protein peaks could be detected when the relative molecular weight ranged from 0 to 50 000. When comparing the protein fingerprint between these two groups, 14 differentially expressed protein peaks were found. By searching SWISS-PRO database, we found 7 670Da peaks accord with C-C motif chemokine 22.SELDI-TOF-MS technique can be used for screening serum protein biomarkers in patients with MF.

To analyze the alterations of serum protein fingerprint in patients with hypertensive disorder complicating pregnancy (HDCP), screen serum biomarker and establish a diagnostic model of HDCP.Surface-enhanced laser desorption lionization-time of flight-mass spectrometry (SELDI-TOF-MS) technology was used to analyze serum including 25 cases of HDCP patients and 30 cases of age-, gravity- and parity-matched healthy term pregnant women on IMAC3-Cu proteinchip before delivery. Biomarker Wizard and Biomarker Pattern software was used to detect protein peaks significantly different between HDCP and controls, and establish a primary diagnostic model of HDCP. This model was further evaluated by blind test using other 16 parts of serum protein fingerprint.Ten protein peaks were significantly different at the molecular range of 2000-50000 (P0.01). A diagnostic model consisting of 5 protein peaks(39 837,6196,15 529, 43 248 and 22 292) was established with 100% (25/25) sensitivity, 90% (27/30) specificity, 89% (25/28) positive predictive value and 100% (27/27) negative predictive value. Blind test generated a sensitivity of 75% and specificity of 75% respectively.Many differential expressed proteins exist in serum of patients with HDCP. The diagnostic model consisting of 5 protein peaks has relative high sensitivity and specificity, and can discriminate HDCP from healthy pregnant

Serum samples from endometrial cancer (EC) patients and healthy females were analyzed using surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to discover the potential diagnostic biomarker for detection of EC. A preliminary training set of spectra derived from 40 EC patients and 30 healthy women were used to develop a proteomic model that effectively discriminated cancer patients from healthy women. The training set had a specificity of 100% and sensitivity of 92.5% in the EC detection. A blind test set, including 20 new cancer cases and 10 healthy women, was used to validate the sensitivity and specificity of this multivariate model, which had a corresponding results of 60% in specificity and 75% in sensitivity, respectively. The combination of SELDI-TOF-MS with bioinformatics tools could help find new biomarkers and establish the detection of EC with high sensitivity and specificity.

Human selenoprotein P (HSelP) is unique protein that contains 10 selenocysteines encoded by 10 inframe UGA, which typically function as stop codon. The function of HSelP remains unclear, in part due to the inability to express it by gene recombinant technique. This study is to investigate expression and purification of recombinant HSelP in prokaryotic expression system, and its activity to induce apoptosis in vitro.The shorter HSelP isoform was cloned. After the selenocysteine (SeCys) at 40th position from N terminus of the HSelP shorter isoform was mutated into cysteine by PCR, it was expressed in E. coli. The expressed product was purified with DEAE column and identified by Western blot. Subsequently, its function on induction of mitochondrial apoptotic activity was studied.The mutant HSelP shorter isoform expressed in prokaryotic system was purified by DEAE column to 90% homogeneity. The purified product, HSelP280m, induced the opening of mitochondrial permeability transition pore (PTP) and decreased the transmembrane potential in a dose-dependent manner. These events could be abolished by PTP specific inhibitors.HSelP280m can induce the opening of mitochondrial PTP, which provides a basis for investigating the structure and function of recombinant HSelP.

To increase the success rate of primary culture of human periodontal ligament fibroblasts (HPLF), and to establish an experimental model for studying HPLF in vitro.The primary cells were isolated from human periodontal ligament by explants with enzymatic digestion method. Morphological analysis and immunocytochemical staining were used to characterize the cell lineage, and growth curve assay to evaluate the biological features of HPLF.The success rate of primary culture of HPLF was 77.8%. Cultured cells were spindle-shaped, and had a positive reaction to antibodies against vimentin, and a negative reaction to antibodies against keratin. Their morphological and biological characteristics were similar to those of typical HPLF. Growth of HPLF obtained by this method was satisfactory.The success rate of primary culture of HPLF is significantly increased by explants combined with enzymatic digestion. The method is simple and feasible.