Age and menopausal status are important factors influencing the serum human epididymis secretory protein 4 level: a prospective cross-sectional study in healthy Chinese people.

BACKGROUND: Human epididymis secretory protein 4 (HE4) is a new ovarian cancer biomarker. The factors influencing HE4 levels are not clear, and the reference data in China are limited. Here, we aim to evaluate the effects of menopause and age on HE4 levels and to provide a possible reference value for HE4 in healthy Chinese people. METHODS: A total of 2493 healthy females aged 40 years or older were recruited from March 2013 to March 2017 with the cooperation of four medical institutions across Beijing, China. The serum levels of HE4 and cancer antigen 125 (CA125) were measured by enzyme-linked immunosorbent assay. The Wilcoxon rank-sum test of variance and a stratified analysis were used to analyze the relationships among age, menopausal status, and levels of HE4 or CA125. Confidence intervals (5%-95%) were determined for reference ranges in different populations. RESULTS: There was a statistically significant difference in median HE4 levels between the post-menopausal (n = 2168) and pre-menopausal groups (n = 325) (36.46 vs. 24.04 pmol/L, Z = -14.41, P < 0.001). HE4 increased significantly with age in the post-menopausal groups (H = 408.18, P < 0.001) but not in the pre-menopausal subjects (Z = -0.43, P = 0.67). The upper 95th percentile of HE4 levels were 44.63 pmol/L for pre-menopausal women, 78.17 pmol/L for post-menopausal women, and 73.3 pmol/L for all women. In the post-menopausal population, the HE4 reference ranges were 13.15 to 47.31, 14.31 to 58.04, 17.06 to 73.51, 24.50 to 115.25, and 35.71 to 212.37 pmol/L for different age groups from forty divided by decade. The CA125 level was affected mainly by menopausal status and not age. CONCLUSIONS: Menopausal status and age were both important factors influencing the level of HE4, and age affected HE4 levels mainly in post-menopausal women. The HE4 level was higher in the post-menopausal population than in the pre-menopausal population and increased with age.

Overexpression of GPNMB predicts an unfavorable outcome of epithelial ovarian cancer.

OBJECTIVE: Glycoprotein non-metastatic protein B (GPNMB) is a transmembrane glycoprotein that is expressed at higher levels in several malignant human tissues than those in matched normal tissues. Thus, GPNMB may serve as an attractive therapeutic target of cancer treatment. In this study, the prognostic value of GPNMB expression was examined in tumors derived from a cohort of patients with epithelial ovarian cancer (EOC). METHODS: GPNMB expression in matched formalin-fixed and paraffin-embedded tissue samples was evaluated by immunohistochemistry (IHC), whereas GPNMB mRNA expression in fresh-frozen biopsy tissues was detected using real-time quantitative PCR (qPCR). Meanwhile, the correlations of GPNMB expression with the clinical characteristics of EOC were assessed. Besides, survival data were analysed using Kaplan-Meier and Cox regression analyses, respectively. RESULTS: GPNMB expression was remarkably upregulated in EOC tissues compared with that in normal ovarian controls at both mRNA and protein levels. In addition, abundant GPNMB expression in EOC was correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.001), residual tumor (P = 0.036), and lymph node metastasis (P = 0.004). Furthermore, results of univariate and multivariate analyses indicated that GPNMB expression level was an independent prognostic factor of the progression-free survival (PFS) and overall survival (OS) (P < 0.001 and P < 0.001, respectively) for EOC patients. CONCLUSION: Upregulated GPNMB levels in EOC patients are associated with dismal prognosis. Moreover, findings in the current study indicate that GPNMB is a potentially useful prognostic predictor of the therapeutic approaches for EOC.

[Complete genome phylogenetic analysis of five H9N2 avian influenza viruses isolated from poultry flocks in Qinghai lake region].

Five H9N2 avian influenza virus strains were isolated from the environmental samples in live poultry market in Qinghai Lake region from July to September, 2012. To evaluate the phylogenetic characteristics of these H9N2 isolates, the eight gene segments were amplified by RT-PCR and sequenced. The phylogenetic and molecular characteristics of the five strains were analyzed. The results showed that the HA genes of five strains shared 93. 2%-99. 1% nucleotide identities with each other, and the NA genes shared 94. 5%-99. 8% nucleotide identities. The HA cleavage site sequence of the A/environment/qinghai/ 017/2012 isolate was PSKSSRGLF, and the HA cleavage site sequences of the other four strains were all PSRSSRGLF. The HA receptor-binding site had the Q226L mutation. The M1 gene segment had the N30D and T215A mutations. The phylogenetic analysis showed that the five strains were similar to the virus A/chicken/Hunan/5260/2005 (H9N2) isolated in Hunan Province, China and were reassortant genotype viruses; the HA, NA, and NS genes belonged to the Y280-like lineage; the MP gene belonged to the G1-like lineage; the NP, PB1, PB2, and PA genes belonged to the F98-like lineage.

[Re-evaluation of interval debulking surgery in advanced epithelial ovarian cancer].

OBJECTIVE: Previous study showed that interval debulking surgery (IDS) may improve the survival of patients with advanced epithelial ovarian cancer (EOC). The precise significance of IDS needs to be evaluated. METHODS: Totally 136 consecutive patients with stage IIIc or IV EOC (including primary peritoneal carcinoma and primary fallopian tube carcinoma) who completed primary debulking surgery (PDS) and platinum-based chemotherapy were enrolled from January 2000 to December 2009 in a retrospective cohort study. The study group was divided into three groups: 65 cases underwent optimal PDS (Group A), 41 cases received chemotherapy alone after suboptimal PDS (Group B), and 30 patients underwent IDS after suboptimal PDS (Group C). All patients received six to eight courses of platinum-based combination chemotherapy (paclitaxel plus carboplatin/cisplatin, cyclophosphamide plus epirubicin and cisplatin). Patients' clinical characteristics, perioperative situation and prognosis were compared. RESULTS: Sixty-five cases (47.8%, 65/136) from 136 patients achieved optimal PDS. For Group C, 77% (23/30) patients obtained optimal debulking surgery after IDS. Intraoperative injury rates were similar between Group B and Group C (P > 0.05). Mild perioperative complications rate was also similar (P > 0.05). Median progression-free survival (PFS) of Group A was 26 months. Median overall survival (OS) of Group B and Group C were 31 months and 40 months, respectively (P = 0.254). Median PFS of Group B and Group C were 13 months and 24 months, respectively (P = 0.289). Although when it came to 20 months after PDS, patients who underwent IDS had a significantly lower progressive disease (PD) rate (Group B 33% versus Group C 61%, P = 0.046), it still showed that there was no significant difference in either OS or PFS of these two groups. Those patients in Group C who obtained no visible residual got similar PFS (27 months) comparing to Group A (26 months, P = 0.730), but OS was still shorter (P = 0.010). CONCLUSIONS: For advanced EOC patients, IDS has little effect on improving survival. While it is safe and acceptable, also may prolong PFS in those patients who got no visible residual after IDS. The results suggest that IDS might be used as an alternative treatment for advanced EOC patients who cannot obtain optimal PDS in certain local hospitals.

Effect of human epididymis protein 4 gene silencing on the malignant phenotype in ovarian cancer.

BACKGROUND: Human epididymis secretory protein 4 (HE4) has been proved to be a promising novel biomarker for the detection of epithelial ovarian carcinomas. Compared with CA125, HE4 assay demonstrated an improved ability to discriminate between pelvic mass with malignant and benign disease. Though it is well known that HE4 is overexpressed in ovarian cancer, however, the role of HE4 in the carcinogenesis and progression of ovarian cancer remains unkown. METHODS: In this study, we explored the role of HE4 in the carcinogenesis and progression of ovarian cancer. We screened nine ovarian cancer cell lines for HE4 expression, and using RNA interference (RNAi), we silenced HE4 gene expression in CaoV3 and SKOV3.ip1 ovarian cancer cell lines. We assessed the effect of HE4 gene silencing on the transformed phenotype by examining the cell cycle, apoptosis, proliferation and transwell migration/invasion in vitro. RESULTS: HE4 gene silencing induces G0/G1 arrest and blocks the progression from the G1 to S phase in CaoV3 and SKOV3.ip1 cells. HE4 knockdown also inhibited cell proliferation, migration and invasion in SKOV3.ip1 cells in vitro. CONCLUSION: HE4 may be involved in the regulation of the cell cycle and promote ovarian cancer migration and invasion.

Reduction and conversion of 2,4,6-trinitrotoluene (TNT) by sulfide under simulated anaerobic conditions.

To account for the fast disappearance of TNT in anaerobic fermentative liquid, we investigated TNT (TNT(0)=50 mg/L) reduction by Na(2)S at 30+/-1 degrees C in two types of buffer systems, a phosphate buffer (PB, system A) and a CH(3)COOH-NaHCO(3) buffer (system B). The effects of pH, sulfide concentration and buffer system on the conversion and reaction rate of TNT were investigated. The effect of different variables on the conversion of TNT decreased in the following order: Na(2)S concentration>pH>buffer system. A kinetics study showed that TNT reduction by Na(2)S occurred in two stages separated by a change point. The observed rate constants of the first stage K(obs-1) were 1 order of magnitude lower than those of the second stage. The TNT conversion rate increased and the time to reach the change point became shorter with increasing Na(2)S concentration and pH. A 5-fold increase in Na(2)S concentration above the theoretical stoichiometric concentration was optimum. Observed rate constants of the first stage K(obs-1) were proportional to the hydrosulfide ion concentration and the conversion rate of TNT was greater and faster in buffer system B than in system A.

[The relationship between rhGH and blood sugar on different ages of severe degree burned patients].

OBJECTIVE: Probe the effects of rhGH on severe degree burned patients' blood sugar in different age of years. METHODS: Elected 210 patients hospitalized in the Third Affiliated Hospital of Wenzhou Medical College from January 2005 to December 2008, who were burned in 48 h, older than 18 years, ever had no diabetes and tumor history and placidly pull through shock stage. Among the patients there were 132 males and 78 females. The age was from 18 to 65 years old, average (40.7 +/- 7.2) years old. The extent of burn were form TBSA 25% to TBSA 86%, average TBSA (40.4 +/- 12.5)%. The depths of burn were from superficial second degree to third degree. All of the total divided into A (18 - 44 years old) and B (> 45 years old)groups. Each group had 105 patients. Two groups were randomly divided into A(1), A(2), A(0) and B(1), B(2), B(0) groups. Each group had 35 patients. The A(1) and B(1) groups were used 0.15 U/(kg.d) growth hormone (Somatropin, S19990021), A(2) and B(2) groups were used 0.2 U/(kg.d) growth hormone, A(0) and B(0) groups were used NS as control. Observed and analyzed the change of blood sugar and insulin amount used in 210 patients. RESULTS: Of all the patients in 6 groups, there were 190 patients finished the experimentation in four weeks. The insulin amount of A(1), A(2), A(0) groups used were (2123.3 +/- 152.3), (2885.6 +/- 148.5), (724.1 +/- 31.1) U, B(1), B(2), B(0) group were (2715.1 +/- 95.3), (3652.2 +/- 198.1), (801.8 +/- 22.2) U. The consequence showed that the number need insulin to control blood sugar in B group was more than A group, as well as using 0.2 U/(kg.d) does to 0.15 U/(kg.d) does, and using growth hormone to no using(P < 0.01). The time that blood sugar of A(1), A(2), B(1), B(2) group recovered to normal range without using insulin were (5.11 +/- 0.82), (4.93 +/- 0.89), (5.2 +/- 0.65), (5.13 +/- 1.02) d (P > 0.05). CONCLUSIONS: The blood sugar's alteration has positive correlation with the age of years and the does of rhGH. As long as normative using rhGH it doesn't induce diabetes.

[Effect of different dressing materials in various combinations on wound microenvironment of donor site in burn patients].

OBJECTIVE: To investigate the effect of dressing materials in various combinations on burn wound microenvironment and healing condition. METHODS: Two hundred donor sites with wounds of 0.3 mm in depth in 186 burn patients, who needed skin grafting and admitted to our ward were enrolled in study, and they were divided into A (with dressing composed of alginate + cotton pad for donor area), B (with dressing composed of vaseline gauze + cotton pad for donor area), C (with dressing composed of alginate + foam dressing for donor area), D (with dressing composed of vaseline gauze + foam dressing for donor area) groups according to random table method. Effect of dressings on wound evaporation and pH value were observed. Bacterial colonization, degree of pain complained by patients after dressing change, and wound healing time in each group were compared. RESULTS: One hundred and eighty-four patients complied with the study, while 2 patients were excluded due to untimely falling-off of the dressing. Wound evaporation in A, B, C, D groups was (35.5 +/- 3.2), (31.3 +/- 2.8), (23.1 +/- 2.9), (18.1 +/- 2.3) mL x h(-1) x m(-2) respectively, among them B group showed optimal effect of keeping humidity (P < 0.01). Wound pH value in A, B, C, D groups was 7.22 +/- 0.06, 7.41 +/- 0.03, 7.05 +/- 0.03, 7.34 +/- 0.06, respectively, among them it was highest in B group. The positive rate of bacteria in D group was highest (22.4%), and lowest in C group (4.0%). Pain was lightest in C group (score was 0.98 +/- 0.12), and most serious in B group (score was 8.14 +/- 0.82). The shortest wound healing time was seen in C group (6.7 +/- 0.8 d), and longest in D group (15.6 +/- 3.5 d). CONCLUSIONS: Application of various dressings on similar wounds can produce different wound microenvironment, which is closely related to wound healing time. Compared with pH value, humidity is the more important factor for wound healing.

[Influence of polyester gauze on evaporation capacity and healing of the surface of microskin graft wound after escharectomy].

OBJECTIVE: To investigate the influence of polyester gauze on evaporation capacity and its clinical effect after escharectomy of deep burn wound and micro-skin grafting. METHODS: Twenty patients with deep burn admitted within 24 hours after injury underwent escharectomy and Meek skin grafting. Two surfaces of wound with the area of about 1% as the whole wound surface were used, one covered by Meek skin graft and polyester gauze as inner dressing (polyester gauze group), and the other covered by split-thickness skin sheet 0.3 mm x 0.3 mm in size and vaseline oil gauze as inner dressing (vaseline oil gauze group). Five days after skin grafting, the evaporation capacities of the surface of inner dressing, wound surface without dressing (nude wound), and normal skin near the wound were tested by evaporation test equipment. The complete healing time and survival rate of skin sheet in both groups were observed. The degree of pain during dressing change was evaluated with visual analog scale. RESULTS: The evaporation capacity of the inner dressing surface of polyester gauze group was (24.8 +/- 5.2) ml x h(-1) x m(-2), significantly lower than those of the vaseline oil gauze group [(35.4 +/- 5.0) ml x h(-1) x m(-2), P < 0.01] and nude wound [(41.3 +/- 4.5) ml x h(-1) x m(-2), P < 0.01], and similar to that of the normal skin near the wound [(21.1 +/- 5.1) ml x h(-1) x m(-2), P > 0.05]. The evaporation capacity of the inner dressing surface of vaseline oil gauze group was significantly lower than nude wound [(40.7 +/- 3.6) ml x h(-1) x m(-2), P < 0.01], but significantly higher than the normal skin near the wound [(21.2 +/- 3.8) ml x h(-1) x m(-2), P < 0.01]. The survival rate of skin sheets of the polyester gauze group was 98% +/- 3%, not significantly different from that of the vaseline oil gauze group (98% +/- 2% , P > 0.05). The wound healing rates on days 10, 15, and 20 of the polyester gauze group were 80% +/- 20%, 96% +/- 7%, and 100% respectively, all significantly higher than those of the vaseline oil gauze group (70% +/- 33%, 81% +/- 21%, and 97% +/- 11% respectively, all P < 0.01). The complete healing time of the polyester gauze group was (13.6 +/- 1.9) days, significantly shorter than that of the vaseline oil gauze group [(16.7 +/- 2.6) days, P < 0.01]. The pain scores during dressing change 5 and 10 days after grafting of the polyester gauze group were (3.2 +/- 0.8) and (4.9 +/- 0.4) respectively, both significantly lower than those of the vaseline oil gauze group [(5.1 +/- 0.6) and (8.2 +/- 0.5) respectively, both P < 0.01]. CONCLUSIONS: Polyester gauze has quite good abilities to retain moisture and can promote the migration and proliferation of epithelial cells, relieves the pain caused by tearing of dressings off the wound, thus raising its acceptability. It is a relatively ideal carrier of skin grafting, as well as a new type of inner cover for the wound.

Randomized controlled trial of the absorbency of four dressings and their effects on the evaporation of burn wounds.

BACKGROUND: Wound dressings are divided into traditional and new types. The new dressings are thought to accelerate wound healing. The purpose of this study was to supplement the scanty data on the absorbency of the new dressings and their effects on evaporation from the burn surface. METHODS: The water absorption rate of four dressings (carbon fiber dressing, hydrogel dressing, silver nanoparticle dressing, and vaseline gauze) were measured by the immersion-weight gain method. A total of 120 inpatients with 10% superficial partial-thickness burn wounds were randomly assigned to four groups, each with 30 participants. Carbon fiber dressing, hydrogel dressing, and silver nanoparticle dressing were used in groups A, B, and C as the primary dressing, and traditional vaseline gauze was used in group D as the control. Multi-spot evaporation from normal skin and naked wound, and from wounds covered with each of the four dressings was measured post-burn on days 1, 3, 5, and 7 by an EP-I evaporimeter under conditions of 21 degrees C - 22 degrees C ambient temperature and 74% - 78% humidity. RESULTS: The absorption rates of the four dressings were 988% with carbon fiber dressing, 96% with silver nanoparticle, 41% with vaseline gauze, and 6% with hydrogel. Evaporation from the naked burn wounds was about 1/3 higher than from normal skin (P < 0.01). Compared with wounds without applied dressing, evaporation from dressed wounds decreased and was time-dependent (P < 0.01). The evaporation of wounds with carbon fiber dressing was the lowest ((13.40 +/- 2.82) mlxh(-1)xm(-2), P < 0.01) on day 1 post-burn, compared with the other groups. CONCLUSION: All four dressings have water retention capacity while carbon fiber dressing has the highest absorption rate and shows the best containment and evaporation from the burn wound.

[Effect of silver nanoparticle dressing on second degree burn wound].

OBJECTIVE: To explore the influence of silver nanoparticle dressing on prevention of infection and healing of the second degree burn wound. METHODS: One hundred and ninety-one burn patients with second degree including superficial and deep burn wound were randomly divided into three groups. Group A including 65 cases was treated by silver nanoparticle dressing on wounds, and group B (63 cases) and group C (63 cases) were treated by 1% silver sulfadiazine cream and vaseline gauze on their wounds, respectively. Dressing was changed daily, and wound swab bacterial cultures were performed before and after dressing change, and also wound healing times were recorded in each patient. RESULTS: Group A and B were similar in their bacterium colonizations on wound after treatment with the silver nanoparticle dressing and 1% silver sulfadiazine cream, and they had a similar effect on reducing bacterium colonization on wound after treatment, while in vaseline gauze group bacterium colonization on wound increased after treatment. In group A the wound healing time of superficial second degree was significantly shorter than those in group B and group C (P < 0.01). In deep second degree wounds the healing time in group A was much shorter than that in group C (P < 0.01), but had no significant difference when compared with group B (P > 0.05). CONCLUSION: Silver nanoparticle dressing can be used on second degree burn wound and can decrease the risk of wound infection and accelerate wound healing.

[Evaluation of effectiveness and safety of a new hydroxyethyl starch used in resuscitation of burn shock].

OBJECTIVE: To evaluate the effectiveness and safety of hydroxyethyl starch (HES 130/ 0.4, 60 g/L) in resuscitation during shock stage of burns. METHODS: Sixty-six burn patients who were admitted to hospital within 2 hours after burn injury requiring fluid resuscitation were enrolled into this study, and they were randomized into HES( n = 33, with HES as a component of fluid resuscitation) and plasma (P, n = 33, with plasma as a component of fluid resuscitation) groups. HES or plasma was given as colloid within 48 postburn hours (PBH), and only albumin [( 111 +/- 4) , ( 105 +/- 5 ) g for each group] were given to the patients during 3 to 7 postburn days (PBD). Heart rate, blood pressure, central venous pressure (CVP) , urine output per hour were measured, gain/loss of body fluid during the first and second 24 PBH were recorded, serum total protein, albumin, hemoglobin( Hb) , prothrombin time (PT) , fibrinogen; platelet ( PLT) , as well as liver and renal function, allergy and bleeding tendency were determined and observed at corresponding time-points. RESULTS: There were no obvious differences in heart rate, blood pressure, CVP and urine output per hour within 24 PBH between the two groups (P > 0.05). Also there was no difference in gain/loss of body fluid during the first and second 24 PBH. The content of hemoglobin on 1 ,3, 7,14 PBD ,and the PT, the content of fibrinogen, the number of PLT on 1,3,14 PBD also exhibited no difference between the two groups (P > 0.05). The serum contents of total protein and albumin in HES group were [(31 +/- 3) g/L, (30 +/- 3)g/L ] on 1 PBD, and [(20.4 +/- 3.6) g/L, (18.4 +/-2.3) g/L] on 3 PBD, which were obviously lower than those in P group [(45 +/- 4) g/L, (39 +/- 3) g/L on 1 PBD, and 1 (24.5 +/- 4.3) g/L, (21.3 +/- 3.9) g/L) on 3 PBD, (P <0. 01). Though the serum content of albumin on 7 PBD was similar in the two groups (P > 0.05), the serum total protein in HES group (40 +/- 4) g/L was markedly lower than that in P group [(45 +/- 4) g/L, P < 0.01] . Within 7 PBD, no abnormal bleeding was found in the two groups, and the liver function and renal function were similar. There were 4 cases showing allergic reaction in plasma group while none in HES group. CONCLUSION: New type of HES can partially substitute plasma and be used in fluid resuscitation for burn patients. However, plasma protein replenishment should still be emphasized.