Effect of Jianpi Shengxue Tablet on Iron Metabolism and Nutritional Status in Patients with Renal Anemia: A Prospective, Randomized, Open, Parallel Controlled and Multicenter Clinical Study.

OBJECTIVE: This study aimed to analyze the clinical efficacy of the Jianpi Shengxue tablet for treating renal anemia. METHODS: A total of 200 patients with renal anemia from December 2020 to December 2022 were enrolled and randomly divided into two groups. Patients in the control group were treated with polysaccharide-iron complex, and those in the experimental group were administered Jianpi Shengxue tablet. After 8 weeks of continuous treatment, the therapeutic outcomes regarding anemia were compared between the two groups. RESULTS: After treatment, the red blood cell (RBC) count, hematocrit (HCT), reticulocyte percentage (RET), ferritin (SF), serum iron (SI), transferrin saturation (TSAT), and serum albumin (ALB) all increased (P<0.01), and the clinical symptom score and total iron binding capacity decreased (P<0.01) in the experimental group. Moreover, the improvements in RBC, HCT, RET, SF, SI, TAST, ALB, and clinical symptoms (fatigue, anorexia, dull skin complexion, numbness of hands and feet) in the experimental group were significantly greater than those in the control group (P<0.05). The total effective rate for treating renal anemia was significantly higher in the experimental group than in the control group (P<0.01). CONCLUSION: The Jianpi Shengxue tablet demonstrates efficacy in treating renal anemia, leading to significant improvements in the laboratory examination results and clinical symptoms of patients with renal anemia.

Interplay Between Long Noncoding RNA ZEB1-AS1 and miR-200s Regulates Osteosarcoma Cell Proliferation and Migration.

In our previous study, we found long noncoding RNA ZEB1-AS1 is upregulated and functions as an oncogene in osteosarcoma. MiR-200 family (miR-200s) functions as tumor suppressor via directly targeting ZEB1 in various cancers. In this study, we further investigate the potential interplay between ZEB1-AS1, miR-200s, and ZEB1 in osteosarcoma. Our results showed that ZEB1-AS1 functions as a molecular sponge for miR-200s and relieves the inhibition of ZEB1 caused by miR-200s. ZEB1-AS1 and miR-200s reciprocally negatively regulate each other. MiR-200s are downregulated in osteosarcoma tissues, and negatively correlated with ZEB1-AS1 and ZEB1 expression levels in osteosarcoma. Functional experiments showed that consistent with ZEB1-AS1 depletion, miR-200s overexpression and ZEB1 depletion both inhibit osteosarcoma cell proliferation and migration. Overexpression of miR-200s partially abolished the effects of ZEB1-AS1 on osteosarcoma cell proliferation and migration. Moreover, the combination of ZEB1-AS1 depletion and miR-200s overexpression significantly inhibits osteosarcoma cell proliferation and migration. In conclusion, this study revealed a novel regulatory mechanism between ZEB1-AS1, miR-200s, and ZEB1. The interplay between ZEB1-AS1 and miR-200s contributes to osteosarcoma cell proliferation and migration, and targeting this interplay could be a promising strategy for osteosarcoma treatment. J. Cell. Biochem. 118: 2250-2260, 2017. © 2017 Wiley Periodicals, Inc.

The FTO gene rs9939609 polymorphism predicts risk of cardiovascular disease: a systematic review and meta-analysis.

OBJECTIVE: Genome-wide association studies have shown that variance in the fat mass- and obesity- associated gene (FTO) is associated with risk of obesity in Europeans and Asians. Since obesity is associated with an increased risk of cardiovascular disease (CVD), several studies have investigated the association between variant in the FTO gene and CVD risk, with inconsistent results. In this study, we performed a meta-analysis to clarify the association of rs9939609 variant (or its proxies [r (2)>0.90]) in the FTO gene with CVD risk. METHODS: Published literature from PubMed and Embase was retrieved. Pooled odds ratios with 95% confidence intervals were calculated using the fixed- or random- effects model. RESULTS: A total of 10 studies (comprising 19,153 CVD cases and 103,720 controls) were included in the meta-analysis. The results indicated that the rs9939609 variant was significantly associated with CVD risk (odds ratio = 1.18, 95% confidence interval = 1.07-1.30, p = 0.001 [Z test], I (2) = 80.6%, p<0.001 [heterogeneity]), and there was an insignificant change after adjustment for body mass index (BMI) and other conventional CVD risk factors (odds ratio = 1.16, 95% confidence interval = 1.05-1.27, p = 0.003 [Z test], I (2) = 75.4%, p<0.001 [heterogeneity]). CONCLUSIONS: The present meta-analysis confirmed the significant association of the rs9939609 variant in the FTO gene with CVD risk, which was independent of BMI and other conventional CVD risk factors.

Screening and identification of serum proteomic biomarkers for gastric adenocarcinoma.

The aim of the present study was to screen for possible serum biomarkers for gastric adenocarcinoma. Surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS) was used to screen serum samples from 109 cases of gastric adenocarcinoma and 106 control subjects (60 healthy subjects, 30 patients with chronic superficial gastritis and 16 cases of chronic atrophic gastritis). The differentially expressed protein peaks were selected and isolated using high performance liquid chromatography (HPLC) and processed with enzyme prior to liquid chromatography-mass spectrometry tandem mass spectrometry (LC-MS/MS) analysis and data mining with software XCalibur program components BioWorks 3.2. Among the gastric cancer cases, three differentially expressed protein peaks were selected as potential serum biomarkers: the m/z peaks at 5,906.5 showed increased expression (8.53±4.33 in the cancer group, and 0.88±0.31 in the control group); the m/z peaks at 6,635.7 and 8,716.3 showed decreased expression (6.54±2.44 and 0.93±0.29, respectively, in the cancer group and 17.56±4.43 and 2.16±0.98, respectively, in the control group) (P<0.01). The m/z peaks at 5,906.5, 6,635.7 and 8,716.3, were identified as fibrinogen α-chain, apolipo-protein A-II and apolipoprotein C-I. The combined use of the three biomarkers distinguished the cancer group patients from the control group samples at a sensitivity of 93.85% (61/65) and a specificity of 94.34% (50/53). In conclusion, fibrinogen α-chain, apolipoprotein A-II and apolipoprotein C-I were identified as potential markers for gastric cancer and appear to have diagnostic value for clinical applications.

Identification of serum amyloid A in the serum of gastric cancer patients by protein expression profiling.

The purpose of this study was to screen serum samples from gastric carcinoma patients and to determine whether serum amyloid A protein (SAA) served as a biomarker. SELDI technology was used to screen for changes in SAA levels in the serum samples. A mass cluster with a mass/charge (m/z) value between 11.1 and 11.9 kDa was identified in the serum samples from gastric carcinoma patients which was much higher than that of the control group. Furthermore, the increase in this m/z peak correlated with the severity of the cancer. High-performance liquid chromatography (HPLC) analysis confirmed that the peak was SAA1. In conclusion, this increase in SAA may be used as a potential biomarker for gastric cancer.

CYP2E1 PstI/RsaI polymorphism and interaction with alcohol consumption in hepatocellular carcinoma susceptibility: evidence from 1,661 cases and 2,317 controls.

Many studies have suggested that cytochrome P450 2E1 (CYP2E1) gene might be involved in the development of hepatocellular carcinoma (HCC). However, the results have been inconsistent. In this study, the authors performed a meta-analysis to clarify the association between Pst I/Rsa polymorphism in the CYP2E1 gene and HCC risk. PubMed and China National Knowledge Infrastructure were searched for eligible publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects model. Fifteen studies (1,661 HCC cases and 2,317 controls) were identified for the data analysis. The overall result showed that there was no statistically significant association between CYP2E1 Pst I/Rsa polymorphism and HCC risk (c2/c2 vs. c1/c1, OR = 0.73, 95% CI 0.50-1.06; c1/c2 vs. c1/c1, OR = 1.00, 95% CI 0.76-1.33; c2/c2+ c1/c2 vs. c1/c1, OR = 0.99, 95% CI 0.77-1.26; c2/c2 vs. c1/c2+ c1/c1, OR = 0.73, 95% CI 0.50-1.06). Further stratified analyses indicated that the habitual alcohol drinkers with c2 alleles were more likely to develop HCC (OR = 1.73, 95% CI 1.19-2.51), compared with the non-habitual drinkers with c1 homozygote. The meta-analysis indicated that CYP2E1 Pst I/Rsa polymorphism was not associated with HCC risk, while the interaction between Pst I/Rsa polymorphism and alcohol consumption increased the risk of HCC.

Effect of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on identifying biomarkers of laryngeal carcinoma.

The aim is to study the serum protein fingerprint of patients with laryngeal carcinoma (LC) and to screen for protein molecules closely related to LC during the onset and progression of the disease with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Serum samples from 68 patients with LC and 117 non-cancer control samples (75 healthy volunteers and 42 Vocal fold polyps). Q10 protein chips and PBSII-C protein chips reader (Ciphergen Biosystems Inc.) were used. The protein fingerprint expression of all the Serum samples and the resulting profiles between cancer and non-cancer groups were analyzed with Biomarker Wizard system. A group of proteomic peaks were detected. Three differently expressed potential biomarkers were identified with the relative molecular weights of 5,915, 6,440 and 9,190 Da. Among the three peaks, the one with m/z 6,440 was down-regulated, and the other two peaks with m/z 5,915 and 9,190 were up-regulated in LC. This diagnostic model could distinguish LC patients from controls with a sensitivity of 92.1% and a specificity of 91.9%. Moreover, blind test data showed a sensitivity of 86.7% and a specificity of 89.1%. The data suggested that SELDI technology could be used to screen proteins with altered expression levels in the serum of LC patients. These protein peaks were considered as specific serum biomarkers of LC and have the potential value for further investigation.

MALDI-TOF MS combined with magnetic beads for detecting serum protein biomarkers and establishment of boosting decision tree model for diagnosis of colorectal cancer.

The aim of present study is to study the serum protein fingerprint of patients with colorectal cancer (CRC) and to screen protein molecules that are closely related to colorectal cancer during the onset and progression of the disease with Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Serum samples from 144 patients with CRC and 120 healthy volunteers were adopted in present study. Weak cation exchange (WCX) magnetic beads and PBSII-C protein chips reader (Ciphergen Biosystems Ins.) were used. The protein fingerprint expression of all the Serum samples and the resulted profiles between cancer and normal groups were analyzed with Biomarker Wizard system. Several proteomic peaks were detected and four potential biomarkers with different expression profiles were identified with their relative molecular weights of 2870.7 Da, 3084 Da, 9180.5 Da, and 13748.8 Da, respectively. Among the four proteins, two proteins with m/z 2870.7 and 3084 were down-regulated, and the other two with m/z 9180.5 and 13748.8 were up-regulated in serum samples from CRC patients. The present diagnostic model could distinguish CRC from healthy controls with the sensitivity of 92.85% and the specificity of 91.25%. Blind test data indicated a sensitivity of 86.95% and a specificity of 85%. The result suggested that MALDI technology could be used to screen critical proteins with differential expression in the serum of CRC patients. These differentially regulated proteins were considered as potential biomarkers for the patients with CRC in the serum and of the potential value for further investigation.

New serum biomarkers for detection of esophageal carcinoma using Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

PURPOSE: To screen for the potential protein biomarkers in serum for the diagnosis of esophageal carcinoma (EC) using proteomic fingerprint technology. METHODS: Proteomic fingerprint technology combining magnetic beads with MALDI-TOF-MS was used to profile and compare the serum proteins from 78 patients with EC and 95 healthy blood donors. Proteomic patterns associated with EC were identified by Biomarker Patterns Software. Model of biomarkers was constructed and evaluated using the Biomarker Patterns Software. RESULTS: A total of 60 discriminating m/z peaks were identified that were related to EC (P < 0.01). The model of biomarkers constructed by the Biomarker Patterns Software based on the four biomarkers (2049.6, 3936.5, 5339.9, and 13748.8 Da) generated excellent separation between the EC and control groups. The sensitivity was 92.5% and the specificity was 88%. Blind test data indicated a sensitivity of 89.5% and a specificity of 84.4%. CONCLUSIONS: Biomarkers for EC can be discovered in serum by MALDI-TOF-MS combining the use of magnetic beads. The pattern of combined markers provides a powerful and reliable diagnostic method for EC with a high sensitivity and specificity.

Discrimination analysis of mass spectrometry proteomics for cervical cancer detection.

To study the serum protein fingerprint of patients with cervical cancer and to screen for protein molecules closely related to cervical cancer during the onset and progression of the disease using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Serum samples from 85 patients with cervical cancer and 80 healthy volunteers. Weak cation exchange (WCX) magnetic beads and PBSII-C protein chips reader (Ciphergen Biosystems Ins.) were used.The protein fingerprint expression of all the serum samples and the resulting profiles between cancer and normal were analyzed with Biomarker Wizard system. A group of proteomic peaks were detected. Three differently expressed potential biomarkers were identified with the relative molecular weights of 3974 Da, 4175 Da, 5906 Da. This diagnostic model can distinguish cervical cancer from healthy controls with a sensitivity of 93.3% and a specificity of 95%. Blind test data indicated a sensitivity of 87.5% and a specificity of 90%. MALDI technology can be used to screen significant proteins of differential expression in the serum of cervical cancer patients. These different proteins could be specific biomarkers of the patients with cervical cancer in the serum and have the potential value of further investigation.

MALDI-TOF MS combined with magnetic beads for detecting serum protein biomarkers and establishment of boosting decision tree model for diagnosis of hepatocellular carcinoma.

No single biologic marker is used in the routine diagnosis of hepatocellular carcinoma (HCC). We screened for potential biomarkers in 142 samples, including samples from 60 patients with HCC, 36 patients with hepatic disease other than HCC, and 46 age- and sex-matched healthy volunteers. Pretreated samples were analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with weak cationic exchange magnetic beads. The diagnostic pattern with a panel of 4 potential protein biomarkers of a mass-to-charge (m/z) ratio of 4,471, 8,936, 11,670, and 13,752 could accurately recognize 56 of 60 patients with HCC, 34 of 36 patients with hepatic disease, and 44 of 46 healthy people. The preliminary data suggest a potential application of MALDI-TOF MS combined with magnetic beads as an effective technology to profile serum proteome, and, with pattern analysis, a diagnostic model comprising 4 potential biomarkers was indicated to differentiate people with hepatic disease and healthy control subjects rapidly and precisely.

[Detection of differentially expressed proteins in the semen of oligospermia patients by SELDI-TOF-MS technology].

OBJECTIVE: To analyze the spectrometric semen protein profiling of oligospermia patients and healthy controls by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS), and to establish a semen marker pattern for the diagnosis of oligospermia. METHODS: Semen samples of 33 oligospermia patients and 31 healthy controls were collected on the CM01O proteinchip. The spectrometric protein profiling was detected by SELDI-TOF-MS and the data analyzed by Biomarker Pattern Software provided by Ciphergen Corp. A primary diagnostic model of oligospermia was established and evaluated by blind test with the 33 patients and 31 healthy controls. RESULTS: A total of 185 protein peaks were detected at the molecular range of 2000-20,000, among which 23 showed significant differences between oligospermia patients and healthy controls (P < 0.05). The diagnostic model consisted of 3 protein peaks, with a sensitivity of 90.9% (30/33) and a specificity of 93.6% (29/31). And the double-blind test generated a sensitivity of 87.8% (29/33) and a specificity of 90.3% (28/31). CONCLUSION: The diagnostic model was successfully established by SELDI-TOF-MS, which could be applied to the differentiation of the spectrometric protein profiling patterns of oligospermia patients and healthy controls.

Proteomic fingerprints for potential application to early diagnosis of severe acute respiratory syndrome.

BACKGROUND: Definitive early-stage diagnosis of severe acute respiratory syndrome (SARS) is important despite the number of laboratory tests that have been developed to complement clinical features and epidemiologic data in case definition. Pathologic changes in response to viral infection might be reflected in proteomic patterns in sera of SARS patients. METHODS: We developed a mass spectrometric decision tree classification algorithm using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Serum samples were grouped into acute SARS (n = 74; <7 days after onset of fever) and non-SARS [n = 1067; fever and influenza A (n = 203), pneumonia (n = 176); lung cancer (n = 29); and healthy controls (n = 659)] cohorts. Diluted samples were applied to WCX-2 ProteinChip arrays (Ciphergen), and the bound proteins were assessed on a ProteinChip Reader (Model PBS II). Bioinformatic calculations were performed with Biomarker Wizard software 3.1.1 (Ciphergen). RESULTS: The discriminatory classifier with a panel of four biomarkers determined in the training set could precisely detect 36 of 37 (sensitivity, 97.3%) acute SARS and 987 of 993 (specificity, 99.4%) non-SARS samples. More importantly, this classifier accurately distinguished acute SARS from fever and influenza with 100% specificity (187 of 187). CONCLUSIONS: This method is suitable for preliminary assessment of SARS and could potentially serve as a useful tool for early diagnosis.