BACKGROUND: Depression among older adults is an important public health issue, and air and noise pollution have been found to contribute to exacerbation of depressive symptoms. This study examined the association of exposure to air and noise pollutants with clinically-newly-diagnosed depressive disorder. The mediating role of individual pro-inflammatory markers was explored. METHODS: We linked National Health Insurance claim data with 2998 healthy community-dwellers aged 55 and above who participated in the Healthy Aging Longitudinal Study between 2009 and 2013. Newly diagnosed depressive disorder was identified using diagnostic codes from the medical claim data. Pollutants were estimated using nationwide land use regression, including PM_2.5 and PM₁₀, carbon monoxide, ozone, nitrogen dioxide, sulfur dioxide, and road traffic noise. Cox proportional hazard models were employed to examine the association between pollutants and newly developed depressive disorders. The mediating effect of serum pro-inflammatory biomarkers on the relationship was examined. RESULTS: Among the 2998 participants, 209 had newly diagnosed depressive disorders. In adjusted Cox proportional hazard models, one interquartile range increase in PM_2.5 (8.53 µg/m³) was associated with a 17.5% increased hazard of developing depressive disorders. Other air pollutants and road traffic noise were not linearly associated with depressive disorder incidence. Levels of serum tumor necrosis factor receptor 1 mediated the relationship between PM_2.5 and survival time to newly onset depressive disorder. CONCLUSION PM_2.5 is related to an increased risk of newly developed depressive disorder among middle-aged and older adults, and the association is partially mediated by the pro-inflammatory marker TNF-R1.
Humans ; Particulate Matter/analysis* ; Male ; Female ; Middle Aged ; Longitudinal Studies ; Aged ; Incidence ; Air Pollutants/analysis* ; Environmental Exposure/adverse effects* ; Taiwan/epidemiology* ; Receptors, Tumor Necrosis Factor, Type I/blood* ; Proportional Hazards Models ; Biomarkers/blood* ; Depression/epidemiology* ; Aged, 80 and over ; Depressive Disorder/chemically induced* ; Risk Factors ; Air Pollution/adverse effects*

OBJECTIVE: To observe the therapeutic effect of acupuncture on cancer-related fatigue (CRF) and to explore its possible mechanism. METHODS: A total of 80 patients with CRF were randomized into an observation group and a control group, and finally 67 patients completed the trial (36 patients in the observation group, 31 patients in the control group). Patients in the control group were treated with conventional chemoradiotherapy and symptomatic treatment, while no particular anti-fatigue intervention was adopted. On the basis of treatment in the control group, acupuncture was applied at Baihui (GV 20), Guanyuan (CV 4), Qihai (CV 6), Fengchi (GB 20), Zusanli (ST 36), Sanyinjiao (SP 6) in the observation group, once a day, 5 times as one course, with 2 days interval between each course, totally 4 courses were required. Before and after treatment, scores of functional assessment of cancer therapy-fatigue (FACT-F) in Chinese and McGill quality of life questionnaire (MQOL), serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α) and soluble TNF receptor-1 (sTNF-R1) were observed in the two groups. RESULTS: ①Compared before treatment, the FACT-F score was decreased after treatment in the observation group (<0.05), while there was no significant difference in the control group (<0.05). The change of the FACT-F score in the observation group was larger than that in the control group (<0.05). ②In the observation group, scores of physiological and psychological dimension were decreased (<0.05), score of social support dimension was increased after the treatment (<0.05). The score changes of physiological, psychological and social support dimension in the observation group were larger than those in the control group (all <0.05). ③After treatment, the serum levels of IL-6, TNF-α and sTNF-R1 were decreased in the observation group (<0.05), while the serum levels of CPR and IL-6 were increased in the control group (<0.05). The serum levels of CPR, IL-6 and TNF-α in the observation were lower than those in the control group (<0.05). CONCLUSION ①Acupuncture can improve the related symptoms of depression, weakness and headache in patients with CRF, strengthen their cognition of the support from society and family, and boost the confidence in curing the disease. ②Acupuncture can effectively down-regulate serum levels of the relative inflammatory factors, which may be its possible mechanism on treating CRF.
Acupuncture Points ; Acupuncture Therapy ; Biomarkers ; blood ; C-Reactive Protein ; analysis ; Fatigue ; etiology ; therapy ; Humans ; Interleukin-6 ; blood ; Neoplasms ; complications ; therapy ; Quality of Life ; Receptors, Tumor Necrosis Factor, Type I ; blood ; Tumor Necrosis Factor-alpha ; blood

Biomarkers for hepatocellular carcinoma (HCC) following curative resection are not currently sufficient for prognostic indication of overall survival (OS) and disease-free survival (DFS). The aim of this study was to investigate the prognostic performance of osteopontin (OPN), matrix metalloproteinase 7 (MMP7), and pregnancy specific glycoprotein 9 (PSG9) in patients with HCC. A total of 179 prospective patients with HCC provided plasma before hepatectomy. Plasma OPN, MMP7, and PSG9 levels were determined by enzyme-linked immunosorbent assay. Correlations between plasma levels, clinical parameters, and outcomes (OS and DFS) were overall analyzed. High OPN ( ⩾ 149.97 ng/mL), MMP7 ( ⩾ 2.28 ng/mL), and PSG9 ( ⩾ 45.59 ng/mL) were prognostic indicators of reduced OS (P < 0.001, P < 0.001, and P = 0.007, respectively). Plasma PSG9 protein level was an independent factor in predicting OS (P = 0.008) and DFS (P = 0.038). Plasma OPN + MMP7 + PSG9 elevation in combination was a prognostic factor for OS (P < 0.001). OPN was demonstrated to be a risk factorassociated OS in stage I patients with HCC and patients with low α-fetoprotein levels ( < 20 ng/mL). These findings suggested that OPN, MMP7, PSG9 and their combined panels may be useful for aiding in tumor recurrence and mortality risk prediction of patients with HCC, particularly in the early stage of HCC carcinogenesis.
Adult ; Aged ; Biomarkers, Tumor ; blood ; Carcinoma, Hepatocellular ; blood ; mortality ; Enzyme-Linked Immunosorbent Assay ; Female ; Hepatectomy ; Humans ; Liver Neoplasms ; blood ; mortality ; Male ; Matrix Metalloproteinase 7 ; blood ; Middle Aged ; Osteopontin ; blood ; Pregnancy-Specific beta 1-Glycoproteins ; analysis ; Prognosis ; Prospective Studies ; Risk Assessment ; Survival Analysis

OBJECTIVE: To screen potential plasma protein biomarkers for the progression of cervical precancerous lesions into cervical carcinoma and analyze their functions. METHODS: Plasma samples obtained from healthy control subjects, patients with low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), cervical cancer (CC), and patients with CC after treatment were enriched for low-abundance proteins for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The MS data of the samples were analyzed using Discoverer 2.2 software, and the differential proteins (peptide coverage ≥20%, unique peptides≥2) were screened by comparison of LSIL, HSIL and CC groups against the control group followed by verification using target proteomics technology. Protein function enrichment and coexpression analyses were carried out to explore the role of the differentially expressed proteins as potential biomarkers and their pathological mechanisms. RESULTS: Compared with the control group, both LSIL group and HSIL group showed 9 differential proteins; 5 differentially expressed proteins were identified in CC group. The proteins ORM2 and HPR showed obvious differential expressions in LSIL and HSIL groups compared with the control group, and could serve as potential biomarkers for the progression of cervical carcinoma. The expression of F9 increased consistently with the lesion progression from LSIL to HSIL and CC, suggesting its value as a potential biomarker for the progression of cervical cancer. CFI and AFM protein levels were obviously decreased in treated patients with CC compared with the patients before treatment, indicating their predictive value for the therapeutic efficacy. Protein function enrichment analysis showed that all these differentially expressed proteins were associated with the complement system and the coagulation cascades pathway. CONCLUSIONS We identified 5 new protein biomarkers (F9, CFI, AFM, HPR, and ORM2) for cervical precancerous lesions and for prognostic evaluation of CC, and combined detection of these biomarkers may help in the evaluation of the development and progression of CC and also in improving the diagnostic sensitivity and specificity of cervical lesions.
Antigens, Neoplasm ; blood ; Biomarkers, Tumor ; blood ; Carrier Proteins ; blood ; Case-Control Studies ; Cervical Intraepithelial Neoplasia ; blood ; diagnosis ; Chromatography, Liquid ; Complement Factor I ; analysis ; Early Detection of Cancer ; Female ; Glycoproteins ; blood ; Haptoglobins ; Humans ; Neoplasm Proteins ; blood ; Orosomucoid ; analysis ; Precancerous Conditions ; blood ; diagnosis ; Serum Albumin, Human ; Tandem Mass Spectrometry ; Uterine Cervical Neoplasms ; blood ; diagnosis

Aged ; Aged, 80 and over ; Androgen Antagonists/therapeutic use* ; Biomarkers, Tumor/blood* ; Dehydroepiandrosterone Sulfate/blood* ; Humans ; Male ; Middle Aged ; Prostatic Neoplasms/mortality* ; Prostatic Neoplasms, Castration-Resistant/mortality* ; Survival Analysis ; Treatment Outcome

OBJECTIVETo explore the predictive value of combination detection of Pgp1 expression in cancer tissue and serum CEA level for the prognosis of colorectal cancer (CRC) patients.

METHODSClinicopathological data, complete 5-year follow-up data and CRC tissue samples of 153 CRC patients with stage I( to II( tumor undergoing radical operation in our department from January 2004 to August 2006 were retrospectively collected. Immunohistochemical staining was used to detect the expression level of Pgp1. The combined evaluation of staining intensity and positive cell percentage was performed to determine the expression level of Pgp1. Pgp1 staining (-) and (+) was defined as low expression; and staining (++) and (+++) as high expression. Electrochemiluminescence immunoassay was used to detect the level of serum CEA. CEA > 5 μg/L was defined as positive. χand Fisher's exact test were performed to analyze the association of Pgp1 expression with CEA level and clinicopathological variables. Moreover, Kaplan-Meier method was used to analyze the survival. Univariate and multivariate Cox proportional hazard regression models were used to evaluate the roles of Pgp1 expression combined with serum CEA level in prognosis prediction.

RESULTSOf 153 patients, 105 were males and 48 females with mean age of 59 (27 to 90) years; 41 cases were rectal cancer, and 112 cases colon cancer; 23 patients were TNM stage I( tumor, and 130 patients stage II( tumor; median follow-up time was 64 months; 30 cases were dead. Positive rate of Pgp1 expression in colorectal cancer tissues was 66.0%(101/153). The expression of Pgp1 was associated with gender, tumor location, and survival during the follow-up (all P<0.05). The preoperative positive rate of serum CEA was 28.1% (43/153). The preoperative serum CEA level was associated with tumor recurrence and survival (all P<0.05). Kaplan-Meier analysis showed the overall 5-year survival rate was 81.7%. The 5-year survival rate of patients with high expression of Pgp1 was 88.1%, which was significantly higher than 69.2% of those with low expression of Pgp1(P=0.003). The 5-year survival rate of patients with preoperative positive serum CEA was 72.1%, which was significantly lower than 86.1% of those with preoperative negative serum CEA(P=0.023). Furthermore, the 5-year survival rate of patients with negative Pgp1 plus positive CEA was 66.7%, which was significantly lower than 91.0% of those with positive Pgp1 plus negative CEA(P=0.002). Univariate analysis showed that gender, Pgp1 expression level, preoperative serum CEA level, and Pgp1 combined with CEA were significantly associated with the prognosis of patients(all P<0.05). Multivariate analysis showed that Pgp1 expression was an independent prognostic factor of CRC [HR(95%CI:1.261 to 64.224), P=0.028].

CONCLUSIONSLow expression of Pgp1 in cancer tissue indicates poor prognosis in patients with stage I( and II( tumor. Combination detection of Pgp1 expression and serum CEA can be applied to predict the prognosis of patients with stage I( and II( colorectal cancer.

Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; blood ; physiology ; Carcinoembryonic Antigen ; blood ; physiology ; Colonic Neoplasms ; physiopathology ; secretion ; Colorectal Neoplasms ; physiopathology ; secretion ; Female ; Fluorescent Antibody Technique ; Humans ; Hyaluronan Receptors ; metabolism ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Proteins ; blood ; physiology ; Neoplasm Recurrence, Local ; physiopathology ; Neoplasm Staging ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Rectal Neoplasms ; physiopathology ; secretion ; Retrospective Studies ; Sex Factors ; Survival Rate

OBJECTIVETo investigate the risk factors of metachronous bone metastasis after radical resection of colorectal cancer within 5 years.

METHODSClinical data of 1 749 patients with colorectal cancer, of whom 50(2.8%) patients developed metastasis to bone after operation, in the Department of Colorectal Surgery, Changhai Hospital of The Second Military Medical University from January 2001 to December 2010 were analyzed retrospectively. Univariate and multivariate analysis were performed to find the risk factors of metachronous bone metastasis from colorectal cancer using Chi square test and Logistic regression, respectively.

RESULTSOf 50 colorectal cancer cases with bone metastasis, 29 were male and 21 were female. The age was ≥ 60 years old in 28 cases. Tumors of 36 cases were located in the rectum and of 14 cases located in the colon. Pathology examination showed 43 cases were adenocarcinomas, 7 cases were mucinous adenocarcinoma. Forty-two cases had T3-4 stage lesions, 30 cases had lymph node metastasis, 14 cases had pulmonary metastasis, and 5 cases had liver metastasis. Univariate Chi square test indicated that factors associated with the metachronous bone metastasis of colorectal cancer within 5 years were tumor site (χ=4.932, P=0.026), preoperative carbohydrate antigen 199 (CA199) level (χ=4.266, P=0.039), lymph node metastasis (χ=13.054, P=0.000) and pulmonary metastasis(χ=35.524, P=0.000). The incidence of bone metastasis in patients with rectal cancer (3.6%, 36/991) was higher compared to those with colon cancer (1.8%, 14/758). The incidence of bone metastasis in patients with higher(> 37 kU/L) preoperative serum CA199 level (4.9%, 12/245) was higher compared to those with lower serum CA199 level (2.5%, 38/1504). The incidence of bone metastasis in patients with lymph node metastasis(4.8%,30/627) and pulmonary metastasis (11.6%, 14/121) was significantly higher compared to those without lymph node metastasis (1.8%, 20/1122) and pulmonary metastasis(2.2%, 36/1628), respectively. Logistic multivariate analysis showed that rectal cancer(OR:0.508, 95%CI:0.268 to 0.963, P=0.038), lymph node metastasis (OR:2.291, 95%CI:1.273 to 4.122, P=0.006) and metachronous pulmonary metastasis(OR:4.796, 95%CI:2.473 to 9.301, P=0.000) were the independent risk factors of metachronous bone metastasis of colorectal cancer within 5 years.

CONCLUSIONPatients with rectal cancer, lymph node metastasis and metachronous pulmonary metastasis are high risk groups of metachronous bone metastasis after radical resection of colorectal cancer within 5 years.

Adenocarcinoma ; surgery ; Aged ; Biomarkers, Tumor ; blood ; Bone Neoplasms ; epidemiology ; secondary ; Chi-Square Distribution ; Colonic Neoplasms ; surgery ; Colorectal Neoplasms ; surgery ; Colorectal Surgery ; statistics & numerical data ; Disease-Free Survival ; Female ; Humans ; Incidence ; Liver Neoplasms ; secondary ; Logistic Models ; Lung Neoplasms ; secondary ; Lymphatic Metastasis ; physiopathology ; Male ; Middle Aged ; Multivariate Analysis ; Prognosis ; Rectal Neoplasms ; surgery ; Retrospective Studies ; Risk Factors

OBJECTIVETo screen and identify the serum specific protein markers of patients with gastric cancer by proteomics technology, and to provide more comprehensive serum protein fingerprint model for the early diagnosis of gastric cancer.

METHODSPreoperative and postoperative blood samples were collected from 60 gastric cancer patients. Mass spectrometry (SELDI-TOF-MS) technology was used to detect and screen serum specific proteins in gastric cancer patients(preoperative group, postoperative group, metastasis group), and the result was compared with normal control group. Gel electrophoresis(TRICINE SDS-OAGE) technology was applied in the separation and purification for those different protein. Matrix assisted laser desorption ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF) technology was used in the identification for the proteins following separation and purification.

RESULTMass spectrometry data of preoperative group and normal group resulted in 15 specific m/z peak(P<0.01). SVM screened by a combination of the highest index model Youden get m/z peak at 6 449.1 protein markers. The protein expression of preoperative group was significantly higher than that of normal group(2 299.3±2 029.3 vs. 509.5±168.3, P<0.01). Mass spectrometry data of preoperative group and postoperative group resulted in 6 specific m/z peak(P<0.01). SVM screened by a combination of the highest Youden index model indentified get m/z peak at 6 449.2 protein markers. The protein expression of preoperative group was significantly higher than that of postoperative group(1 247.9±685.0 vs. 476.5±157.8, P<0.01). Mass spectrometry data of preoperative group and metastasis group resulted in 12 specific m/z peak (P<0.01). SVM screened by a combination of the highest Youden index model indentified get m/z peak at 6 448.9 protein markers. The protein expression of metastasis group was higher than that of preoperative group(1 506.9±1 036.5 vs. 649.7±621.0). MALDI-TOF/TOF identified that the protein with m/z peak at 6 449 was Apo CIII(.

CONCLUSIONApo CIII( may be the specific serum protein marker of gastric cancer, which may provide a more comprehensive serum protein fingerprint model for the early diagnosis of gastric cancer and a new way for further research.

Biomarkers, Tumor ; blood ; Blood Proteins ; analysis ; Humans ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Stomach Neoplasms ; blood ; diagnosis

OBJECTIVETo investigate the predictive value of preoperative Glasgow prognostic score (GPS) for the postoperative complications and survival in patients with colorectal cancer (CRC) undergoing laparoscopic radical resection.

METHODSThis retrospective study was conducted in the Beijing Hospital between January 2009 and January 2012. A total of 228 patients with primary CRC undergoing laparoscopic radical resection were analyzed. The GPS was constructed based on routine preoperative blood tests of C-reactive protein and serum albumin. The patients were classified into three groups according to GPS (GPS 0, 1, 2 groups). Survival curves were described by the Kaplan-Meier method and compared by the Log-rank test. The univariate and multivariate analyses were performed with the Cox proportional hazard model to identify the influence of GPS on prognosis in patients with CRC undergoing laparoscopic radical resection.

RESULTSPreoperative CRP level was increased in 48 cases (21.1%), and preoperative serum albumin level was decreased in 104 cases (45.6%) in the whole group. These 228 patients were classified into 99, 105 and 24 patients in GPS 0, 1, 2 group respectively. GPS was significantly associated with age, preoperative body mass index (BMI), carcinoembryonic antigen (CEA), CA19-9, tumor location, tumor differentiation and TNM stage (all P<0.05). Postoperative complication rates of GPS 0, 1, 2 group were 6.1%, 14.3% and 70.8% respectively (χ=59.147, P=0.000). Serious postoperative complication rates were 3.0%, 6.7% and 58.3% respectively (χ=65.807, P=0.000). Univariate and multivariate analyses revealed that GPS was an independent risk factor of postoperative complications(HR=21.611, 95%CI: 5.936-78.681, P=0.000) and severe complications (HR=35.833, 95%CI: 7.364-174.355, P = 0.000). The 5-year survival rate was 50% and the average total survival time was 58.2 (95% CI: 54.6-61.7) months in the whole group. The median overall survival time in GPS 0, 1, 2 group was 74.6(95%CI: 70.4-78.7) months, 49.8(95%CI: 45.2-54.4) months and 27.8 (95%CI: 21.8-33.8) months respectively(χ=98.425, P=0.000). The median disease-free survival time was 73.9(95%CI: 69.2-78.7) months, 47.4 (95% CI: 41.6-53.1) months and 19.9 (95%CI: 14.8-25.0) months respectively (χ=91.305, P=0.000). GPS was an independent risk factor of disease-free survival (HR=4.840, 95%CI: 2.413-9.709, P=0.000) and overall survival (HR=6.267, 95%CI: 3.073-12.784, P=0.000).

CONCLUSIONSGPS can be used as an effective predictor of the prognosis for patients with CRC undergoing laparoscopic radical surgery. Higher GPS suggests more postoperative complications and worse prognosis.

Adult ; Aged ; Biomarkers, Tumor ; analysis ; C-Reactive Protein ; analysis ; CA-19-9 Antigen ; analysis ; Carcinoembryonic Antigen ; analysis ; Colorectal Neoplasms ; blood ; surgery ; Disease-Free Survival ; Female ; Humans ; Laparoscopy ; Male ; Middle Aged ; Multivariate Analysis ; Postoperative Complications ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Serum Albumin ; Survival Rate

Pretransplant alpha-fetoprotein (AFP) is a useful tumor marker predicting recurrence of hepatocellular carcinoma (HCC). Little is known, however, about the relationship between changes in AFP concentration and prognosis. This study investigated the clinical significance of change in peri-transplant AFP level as a predictor of HCC recurrence. Data from 125 HCC patients with elevated pretransplant AFP level who underwent liver transplantation (LT) between February 2000 and December 2010 were retrospectively reviewed. Patients with AFP normalization within 1 month after LT were classified into the rapid normalization group (n = 97), with all other patients classified into the non-rapid normalization group (n = 28). Tumor recurrence was observed in 17 of the 97 patients (17.5%) with rapid normalization; of these, 11 patients had high AFP levels and six had normal levels at recurrence. In contrast, tumor recurrence was observed in 24 of the 28 patients (85.7%) without rapid normalization, with all 24 having high AFP levels at recurrence. Multivariate analysis showed that non-rapid normalization (harzard ratio [HR], 4.41, P < 0.001), sex (HR, 3.26, P = 0.03), tumor size (HR, 1.15, P = 0.001), and microvascular invasion (HR, 2.65, P = 0.005) were independent risk factors for recurrence. In conclusion, rapid normalization of post-LT AFP level at 1 month is a useful clinical marker for HCC recurrence. Therefore, an adjuvant strategy and/or intensive screening are needed for patients who do not show rapid normalization.
Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Carcinoma, Hepatocellular/blood/mortality/*pathology/therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms/blood/mortality/*pathology/therapy ; *Liver Transplantation ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; alpha-Fetoproteins/analysis