The association between systemic inflammatory response index and contrast-associated acute kidney injury in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: The systemic inflammatory response index (SIRI), served as a novel inflammatory biomarker, is the synthesis of neutrophils, monocytes and lymphocytes. AIMS: We hypothesized that SIRI has predictive value for contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: We retrospectively observed 5685 patients undergoing elective PCI from January 2012 to December 2018. Venous blood samples were collected to obtain the experimental data on the day of admission or the morning of the next day. SIRI = neutrophil count × monocyte count/lymphocyte count. CA-AKI was defined as an increase of 50% or 0.3 mg/dl in SCr from baseline within 48 h after contrast exposure. RESULTS: The incidence of CA-AKI was 6.1% (n = 352). The best cutoff value of SIRI for predicting CA-AKI was 1.39, with a sensitivity of 52.3% and a specificity of 67.3%. [AUC: 0.620, 95% confidence interval (CI): 0.590-0.651, p < 0.001]. After adjusting for potential confounders, multivariate analysis showed that the high SIRI group (SIRI > 1.39) was a strong independent predictor of CA-AKI in patients undergoing elective PCI compared with the low SIRI group (SIRI ≤ 1.39) (odds ratio = 1.642, 95% CI: 1.274-2.116, p < 0.001). Additionally, COX regression analysis showed that SIRI > 1.39 was significantly associated with long-term mortality at a median follow-up of 2.8 years. [Hazard ratio (HR)=1.448, 95%CI: 1.188-1.765; p < 0.001]. Besides, Kaplan-Meier survival curve also indicated that the cumulative rate of mortality was considerably higher in the high SIRI group. CONCLUSIONS: High levels of SIRI are independent predictors of CA-AKI and long-term mortality in patients undergoing elective PCI.

The Association Between the Albumin-Bilirubin Score and Contrast-Associated Acute Kidney Injury in Patients Undergoing Elective Percutaneous Coronary Intervention.

The albumin-bilirubin (ALBI) score is considered an effective and convenient scoring system for assessing liver function. We hypothesized that the ALBI score was predictive of contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). We retrospectively observed 5629 patients undergoing elective PCI. Contrast-associated acute kidney injury is defined as a 50% or 0.3 mg/dl increase in baseline serum creatinine levels within 48 h of contrast exposure. The incidence of CA-AKI was 6.2% (n = 350). After adjusting for potential confounding factors, multivariate analysis showed that the ALBI score was an independent predictor of CA-AKI (P = .002). A restricted cubic spline analysis confirmed approximately linear relationships between the ALBI score and risks of CA-AKI. Furthermore, at a median follow-up of 2.8 years, multivariate Cox regression analysis indicated that the ALBI score was an independent risk factor for long-term mortality (P < .001). The ALBI score was closely related to the occurrence of CA-AKI and long-term mortality in patients who underwent elective PCI. This score might be useful for risk stratification in high-risk patient groups to predict CA-AKI.

A Pilot Study About the Role of PANoptosis-Based Genes in Atherosclerosis Development.

Background: As a chronic inflammatory disease, atherosclerosis (AS) and ischemia events are primarily affected by inflammation in AS. PANoptosis has been implicated in many human systemic disorders, including infection, cancer, neurodegeneration, and inflammation. On the other hand, little is understood about PANoptosis's function in AS. Methods: We used consensus clustering to divide the GSE100927 dataset into two panoptosis-related subgroups. PANoptosis-associated genes were screened by differential analysis and weighted gene co-expression network analysis (WGCNA) and enriched by ClueGO software. Investigating LASSO regression and MCODE to identify AS Diagnostic Markers. Immunoinfiltration analysis and single-cell analysis were used to search for cell types associated with the diagnostic genes. Final validation was performed by polymerase chain reaction (PCR). Results: We classified the GSE100927 dataset into two PANoptosis-related subtypes based on the expression of PANoptosis-related genes (PRGs) using consensus clustering. A total of 36 PANoptosis-associated genes were screened in the differentially expressed genes and WGCNA-related module. 4 hub genes were identified by MCODE and LASSO regression, and 3 AS diagnostic markers (ACP5, CCL3, HMOX1) were screened by external validation set. Immunoinfiltration analysis and single-cell analysis showed that the three diagnostic markers were associated with macrophages, and PCR results demonstrated that ACP5 and HMOX1 could be used as AS diagnostic markers. Conclusion: Our study identified ACP5 and HMOX1 as diagnostic genes for AS that may be associated with PANoptosis. ACP5 and HMOX1 may be involved in the pathogenesis of AS by regulating macrophage PANoptosis.

Predictive Value of Systemic Inflammation Score for Contrast-Associated Acute Kidney Injury and Adverse Outcomes Among Patients Undergoing Elective Percutaneous Coronary Intervention.

Purpose: Prior research has demonstrated a key role of systemic inflammatory state in the pathogenesis and progression of contrast-associated acute kidney injury (CA-AKI). Recently, the systemic inflammation score (SIS) has been introduced to evaluate the inflammatory status, utilizing the lymphocyte-to-monocyte ratio (LMR) and albumin. The primary objective of this study was to determine whether the SIS can predict CA-AKI and long-term prognosis in patients undergoing elective percutaneous coronary intervention (PCI). Patients and Methods: A total of 5726 patients who underwent elective PCI were included from January 2012 to December 2018. The primary outcome was CA-AKI, defined as an increase in serum creatinine (SCr) ≥0.3 mg/dl or ≥50% than baseline SCr within 48 h after the PCI procedure. The secondary outcome was long-term mortality. All patients were classified into low- and high-SIS groups. Results: During hospitalization, 349 (6.1%) patients developed CA-AKI. Multivariate logistic regression analysis showed that patients in the high SIS group had a 1.47-fold higher risk of developing CA-AKI than those in the low SIS group [odds ratio (OR): 1.50, 95% confidence interval (CI): 1.12-2.01, P =0.006]. Furthermore, the SIS showed the greatest prediction performance for CA-AKI compared with other inflammatory hematological ratios. In the multivariate Cox regression analysis, the high SIS group was found to be closely associated with long-term mortality [hazard ratio (HR): 1.58, 95% CI: 1.26-1.97, P <0.001, vs low SIS group]. The Kaplan-Meier curve analysis also demonstrated a difference in long-term mortality between the two groups (Log rank test, P <0.001). Conclusion: The SIS was closely associated with CA-AKI and long-term mortality in patients after elective PCI. Thus, more attention should be paid to exploring the potential benefits of anti-inflammatory strategies in preventing CA-AKI and improving the prognosis of patients undergoing PCI.

A glutamatergic basal forebrain to midbrain circuit mediates wakefulness and defensive behavior.

Defensive behavior, a group of responses that evolved due to threatening stimuli, is crucial for animal survival in the natural environment. For defensive measures to be timely and successful, a high arousal state and immediate sleep-to-wakefulness transition are required. Recently, the glutamatergic basal forebrain (BF) has been implicated in sleep-wake regulation; however, the associated physiological functions and underlying neural circuits remain unknown. Here, using in vivo fiber photometry, we found that BF glutamatergic neuron is activated by various threatening stimuli, including predator odor, looming threat, sound, and tail suspension. Optogenetic activation of BF glutamatergic neurons induced a series of context-dependent defensive behaviors in mice, including escape, fleeing, avoidance, and hiding. Similar to the effects of activated BF glutamatergic cell body, photoactivation of BF glutamatergic terminals in the ventral tegmental area (VTA) strongly drove defensive behaviors in mice. Using synchronous electroencephalogram (EEG)/electromyogram (EMG) recording, we showed that photoactivation of the glutamatergic BF-VTA pathway produced an immediate transition from sleep to wakefulness and significantly increased wakefulness. Collectively, our results clearly demonstrated that the glutamatergic BF is a key neural substrate involved in wakefulness and defensive behaviors, and encodes these behaviors through glutamatergic BF-VTA pathway. Overexcitation of the glutamatergic BF-VTA pathway may be implicated in clinical psychiatric diseases characterized by exaggerated defensive responses, such as autism spectrum disorders.

Inflammation-related adverse reactions following vaccination potentially indicate a stronger immune response.

Concerns about vaccine safety are an important reason for vaccine hesitancy, however, limited information is available on whether common adverse reactions following vaccination affect the immune response. Data from three clinical trials of recombinant vaccines were used in this post hoc analysis to assess the correlation between inflammation-related solicited adverse reactions (ISARs, including local pain, redness, swelling or induration and systematic fever) and immune responses after vaccination. In the phase III trial of the bivalent HPV-16/18 vaccine (Cecolin®), the geometric mean concentrations (GMCs) for IgG anti-HPV-16 and -18 (P<0.001) were significantly higher in participants with any ISAR following vaccination than in those without an ISAR. Local pain, induration, swelling and systemic fever were significantly correlated with higher GMCs for IgG anti-HPV-16 and/or anti-HPV-18, respectively. Furthermore, the analyses of the immunogenicity bridging study of Cecolin® and the phase III trial of a hepatitis E vaccine yielded similar results. Based on these results, we built a scoring model to quantify the inflammation reactions and found that the high score of ISAR indicates the strong vaccine-induced antibody level. In conclusion, this study suggests inflammation-related adverse reactions following vaccination potentially indicate a stronger immune response.

Regeneration of critical-sized mandibular defect using a 3D-printed hydroxyapatite-based scaffold: An exploratory study.

BACKGROUND: Three-dimensional (3D) printing has become an available technology to fabricate customized tissue engineering scaffolds with delicate architecture. This exploratory study aimed to evaluate the potential of a 3D-printed hydroxyapatite-based scaffold as a biomaterial for obtaining guided bone regeneration (GBR) in vivo. METHODS: Scaffolds composed of 90% hydroxyapatite and 10% poly(lactic-co-glycolic acid) were printed using a microextrusion process to fit 4 mm diameter and 0.5 mm thick through-and-through osseous defects on the mandibular ramus of rats, with unfilled defects serving as controls. Specimens were analyzed for regeneration-associated gene expression on day 7, and micro-computed tomography (micro-CT) and histology assessments were carried out on day 28. RESULTS: The scaffolds were 3.56 ± 0.43 mm (x-axis) and 4.02 ± 0.44 mm (y-axis) in diameter and 0.542 ± 0.035 mm thick (z-axis), with a mean pore size of 0.420 ± 0.028 × 0.328 ± 0.005 mm2 . Most scaffolds fit the defects well. Type I collagen, VEGF, and Cbfa1 were upregulated in the scaffold-treated defects by day 7. By day 28, de novo osteogenesis and scaffold-tissue integration were evident in the scaffold-treated defects, and entire mineralized tissue, as well as newly formed bone, was significantly promoted, as seen in the micro-CT and histologic analyses. CONCLUSION: The 3D-printed hydroxyapatite-based scaffold showed acceptable dimensional stability and demonstrated favorable osteoregenerative capability that fulfilled the need for GBR.

Association of Peroxiredoxin 1 and brain-derived neurotrophic factor serum levels with depression and anxiety symptoms in patients with irritable bowel syndrome.

BACKGROUND: Oxidative stress is considered a possible mechanism of irritable bowel syndrome (IBS) and depression. This study determined the possible association of serum peroxiredoxin 1 (PRDX1; a key antioxidant enzyme) and brain-derived neurotrophic factor (BDNF) with anxiety and depression symptoms in IBS patients. METHODS: According to the Rome IV diagnostic criteria, 177 IBS patients from February 2019 to July 2019 were included. Serum levels of PRDX1, BDNF, and TNFα were detected by enzyme-linked immunosorbent assay. Levels of anxiety and depression were assessed with the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS). RESULTS: Compared with normal IBS patients, patients with anxiety and depression symptoms had significantly higher serum PRDX1 (p<0.001; p=0.002) and TNFα (p<0.001; p = 0.002) and significantly lower BDNF (p < 0.001; p = 0.002). Serum PRDX1 (r = 0.659, p < 0.001; r = 0.466, p < 0.001) and TNFα (r = 0.531, p < 0.001; r = 0.449, p < 0.001) were positively correlated with SAS and SDS, respectively, whereas BDNF was negatively correlated with SAS (r = 0.594, p < 0.001) and SDS (r = 0.534, p < 0.001). Multivariable regression analysis revealed that IBS severity, BDNF, and PRDX1 were significant predictors of anxiety. BDNF was also a significant predictor of depression. CONCLUSION: Elevated PRDX1 and decreased BDNF in serum may be closely related to psychological symptoms in IBS. Results of this study suggested that PRDX1 may be an important target for IBS treatment in fighting against intestinal and psychological symptoms.

Preclinical evaluation of a 3D-printed hydroxyapatite/poly(lactic-co-glycolic acid) scaffold for ridge augmentation.

BACKGROUND/PURPOSE: Supracrestal ridge augmentation (SRA) is a major challenge for clinicians. This study investigated the efficacy of a 3D-printed (3DP) hydroxyapatite/poly(lactic-co-glycolic acid) (HA/PLGA) scaffold as a potential biologic for SRA. METHODS: Scaffolds that were 5 mm in diameter and 2.5-mm thick with a 1.2-mm diameter through-and-through central hole composed of 90% HA and 10% PLGA were printed using an extrusion-based bioprinter. The HA/PLGA scaffold was fixed with a 1.2-mm titanium mini-implant on the buccal surface of rat mandible (Ti-HPS), and the outcome of SRA were compared with sites treated with a titanium mini-implant alone (control) and a titanium mini-implant covered with deproteinized bovine bone-derived matrix (Ti-DBBM) at 4 and 8 weeks by microcomputed tomography (micro-CT), back-scattered SEM, and histology assessments. RESULTS: The HA/PLGA scaffolds were 2.486 ± 0.082 mm thick with an outer diameter of 4.543 ± 0.057 mm and an inner diameter of 1.089 ± 0.045 mm, and the pore dimensions were 0.48-0.52 mm. There was significantly more mineralized tissue in the Ti-DBBM and Ti-HPS groups than in the control group at both time points. Newly formed bone (NB) was well-integrated with the DBBM and HA/PLGA scaffolds. The framework of the 3DP-HA/PLGA scaffold remained in place, and NB-implant contact (NBIC) was advanced to the middle level in the Ti-HPS group until 8 weeks, whereas dispersion of DBBM with a lower level NBIC was noted in the Ti-DBBM group at both time points. CONCLUSION: The 3DP HA/PLGA scaffold maintains supracrestal space and demonstrates osteoconductivity to facilitate SRA.

Immunogenicity of an Escherichia coli-produced bivalent human papillomavirus vaccine under different vaccination intervals.

A new Escherichia coli-produced human papillomavirus (HPV)-16/18 vaccine has been shown to be safe and highly efficacious and was recently licensed in China. As a post hoc analysis of the phase III trial, this study aimed to assess the impact of vaccination time deviations on the specific antibody response and guide the better usage of this vaccine in the real world. A total of 3689 healthy women aged 18-45 years old were randomly assigned to receive the bivalent HPV-16/18 vaccine according to a 0-, 1- and 6-month schedule with a wide vaccination interval. The first vaccination interval between the 1st and 2nd doses (the 1st interval) was divided into three groups: 28-40 d, 41-50 d and 51-60 d. The second vaccination interval between the 2nd and 3rd doses (the 2nd interval) was divided into three groups: 103-139 d, 140-160 d and 161-198 d. The reverse cumulative curves for the IgG of the three groups with different 1st vaccination intervals or with different 2nd vaccination intervals at month 7 almost overlapped for both HPV-16 and HPV-18. Compared with the standard vaccination schedule (a 1st interval of 28-40 d and a 2nd interval of 140-160 d) subgroup, all the subgroups had GMC ratios greater than 0.83, with the lower limit of 95% CIs higher than 0.64. In conclusion, a slight deviation in the vaccination time of the 2nd and 3rd doses has only a minor, insignificant impact on the immune response induced by the Escherichia coli-produced HPV-16/18 vaccine.

Core-Shell poly-(D,l-Lactide-co-Glycolide)-chitosan Nanospheres with simvastatin-doxycycline for periodontal and osseous repair.

This study aimed to evaluated the potential of core-shell poly(D,l-lactide-co-glycolide)-chitosan (PLGA-chitosan) nanospheres encapsulating simvastatin (SIM) and doxycycline (DOX) for promoting periodontal and large-sized osseous defects. SIM, and/or DOX were encapsulated in PLGA-chitosan nanospheres using double emulsion technique and were delivered to sites of experimental periodontitis and large-sized mandibular osseous defects of rats for 1-4 weeks. The resultant nanospheres were ~ 200 nm diameter with distinct core-shell structure and released SIM and DOX sustainably for 28 days. DOX and SIM-DOX nanospheres significantly inhibited P. gingivalis and S. sanguinis. In experimental periodontitis sites, SIM-DOX nanospheres significantly down-regulated IL-1b and MMP-8 and significantly reduced bone loss. In mandibular osseous defects, VEGF was up-regulated, and osteogenesis was significantly augmented with SIM nanospheres treatment. In conclusion, core-shell PLGA-chitosan nanospheres released SIM and DOX sustainably. SIM-DOX and SIM nanospheres could be considered to promote the repair of infected periodontal sites and non-infected osseous defects respectively.

Efficacy, Safety, and Immunogenicity of an Escherichia coli-Produced Bivalent Human Papillomavirus Vaccine: An Interim Analysis of a Randomized Clinical Trial.

BACKGROUND: The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. METHODS: A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18-45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission. RESULTS: In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. CONCLUSIONS: The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18-associated high-grade genital lesions and persistent infection in women.

Immunogenicity noninferiority study of 2 doses and 3 doses of an Escherichia coli-produced HPV bivalent vaccine in girls vs. 3 doses in young women.

A new HPV-16/18 bivalent vaccine expressed by the Escherichia coli has been proven to be efficacious in adult women. A randomized, immunogenicity noninferiority study of this candidate vaccine was conducted in December 2015 in China. Girls aged 9-14 years were randomized to receive 2 doses at months 0 and 6 (n=301) or 3 doses at months 0, 1 and 6 (n=304). Girls aged 15-17 years (n=149) and women aged 18-26 years (n=225) received 3 doses. The objectives included noninferiority analysis of the IgG geometric mean concentration (GMC) ratio (95% CI, lower bound>0.5) to HPV-16 and HPV-18 at month 7 in girls compared with women. In the per-protocol set, the GMC ratio of IgG was noninferior for girls aged 9-17 years receiving 3 doses compared with women (1.76 (95% CI, 1.56, 1.99) for HPV-16 and 1.93 (95% CI, 1.69, 2.21) for HPV-18) and noninferior for girls aged 9-14 years receiving 2 doses compared with women (1.45 (95% CI, 1.25, 1.62) for HPV-16 and 1.17 (95% CI, 1.02, 1.33) for HPV-18). Noninferiority was also demonstrated for neutralizing antibodies. The immunogenicity of the HPV vaccine in girls receiving 3 or 2 doses was noninferior compared with that in young adult women.

Lot-to-lot consistency study of an Escherichia coli-produced bivalent human papillomavirus vaccine in adult women: a randomized trial.

An Escherichia. coli-produced HPV-16/18 bivalent vaccine has been proved to be well-tolerated and highly efficacious against diseases associated with vaccine HPV types. As a part of the multi-center, randomized, double-blind phase III clinical trial, this lot-to-lot consistency study aimed to assess the safety and immunogenicity consistency of this novel HPV vaccine, which is also one of the objectives of the phase III trial. A total of 3689 healthy women aged 18-45 years were enrolled and randomly assigned 1:1:1 to three lots of the HPV vaccine groups. The primary outcomes were the IgG antibody level at 1 month after the last dose (month 7). In the immunogenicity per-protocol set (PPS), almost all of the participants seroconverted at month 7 and remained seropositive at month 42. For each paired comparison of the three lot groups, the two-sides of 90% CIs of GMC ratios for both IgG and neutralizing antibodies for HPV-16 and HPV-18 at month 7 were within the equivalence interval [0.5, 2]. Lot consistency was also demonstrated at month 42. The majority of recorded solicited reactions were mild or moderate. The incidences of solicited reactions of Lot 2 and Lot 3 were slightly higher than Lot 1. However, the incidences of solicited reactions of ≥ grade 3 and solicited reactions by symptoms were all similar among the three lot groups. None of the SAEs was considered related to vaccination by the investigator. In conclusion, this study demonstrates lot-to-lot consistency of the 3 consecutive lots of the E. coli-produced HPV-16/18 bivalent vaccine.

Peroxiredoxin 1 as an inflammatory marker in diarrhea-predominant and postinfectious irritable bowel syndrome.

BACKGROUND: Low-grade inflammation occurs in some patients with irritable bowel syndrome (IBS). However, the exact inflammatory markers of IBS and the relationship of these markers with IBS subtypes and symptoms are poorly defined. Peroxiredoxin 1 (PRDX1) plays an important role in inflammatory responses, including intestinal inflammation. We investigated whether PRDX1 is associated with the diagnosis, subtypes, and symptom severity of IBS. METHODS: A total of 177 IBS patients and 174 sex- and age-matched healthy controls (HCs) were recruited. The PRDX1 levels in the sera and colonic mucosa of the participants were detected by enzyme-linked immunosorbent assays and immunohistochemistry. The severity of IBS symptoms was assessed using the IBS Severity Scoring System (SSS) questionnaire. RESULTS: The PRDX1 levels in the sera (F = 71.81, P < .001) and colonic mucosa (F = 5.359, P < .001) of postinfectious (PI-IBS) and diarrhea-predominant IBS (IBS-D) groups were significantly higher than those of the other three IBS subtypes and HC group. The PRDX1 level in the serum and colonic mucosa of IBS-D (serum, P < .01, mucosa, P < .001) and PI-IBS (serum, P < .05, mucosa, P < .001) groups with the most severe symptoms was significantly higher than that in the groups with mild and moderate symptoms. Correlation analysis revealed that in patients with IBS-D (P < .001) and PI-IBS (P < .05), the levels of PRDX1 and TNF-α in sera had a significant positive correlation with IBS-SSS. CONCLUSION: Elevated PRDX1 in the serum and colon mucosa may be closely related to the progression of IBS (especially IBS-D and PI-IBS) and the expression of gastrointestinal symptoms.

Immunogenicity and safety of an E. coli-produced bivalent human papillomavirus (type 16 and 18) vaccine: A randomized controlled phase 2 clinical trial.

BACKGROUND: This study aimed to investigate the dosage, immunogenicity and safety profile of a novel human papillomavirus (HPV) types 16 and 18 bivalent vaccine produced by E. coli. METHODS: This randomized, double-blinded, controlled phase 2 trial enrolled women aged 18-25 years in China. Totally 1600 eligible participants were randomized to receive 90µg, 60µg, or 30µg of the recombinant HPV 16/18 bivalent vaccine or the control hepatitis B vaccine on a 0, 1 and 6 month schedule. The designated doses are the combined micrograms of HPV16 and 18 VLPs with dose ratio of 2:1. The immunogenicity of the vaccines was assessed by measuring anti-HPV 16 and 18 neutralizing antibodies and total IgG antibodies. Safety of the vaccine was assessed. RESULTS: All but one of the seronegative participants who received 3 doses of the HPV vaccines seroconverted at month 7 for anti-HPV 16/18 neutralizing antibodies and IgG antibodies. For HPV 16, the geometric mean titers (GMTs) of the neutralizing antibodies were similar between the 60µg (GMT=10,548) and 90µg (GMT=12,505) HPV vaccine groups and were significantly higher than those in the 30µg (GMT=7596) group. For HPV 18, the GMTs of the neutralizing antibodies were similar among the 3 groups. The HPV vaccine was well tolerated. No vaccine-associated serious adverse events were identified. CONCLUSION: The prokaryotic-expressed HPV vaccine is safe and immunogenic in women aged 18-25 years. The 60µg dosage formulation was selected for further investigation for efficacy. CLINICAL TRIALS REGISTRATION: NCT01356823.

Correlation between ELISA and pseudovirion-based neutralisation assay for detecting antibodies against human papillomavirus acquired by natural infection or by vaccination.

A pseudovirion-based neutralisation assay (PBNA) has been considered the gold standard for measuring specific antibody responses against human papillomavirus (HPV). However, this assay is labor intensive and therefore very difficult to implement in large-scale studies. Previous studies have evaluated the agreement between virus-like particle (VLP)-based ELISA and PBNA for measuring HPV vaccine-induced antibodies. However, the concordance of these assays to detect antibodies induced by natural infection has not yet been fully elucidated. In this study, the results of an Escherichia coli (E. coli)-expressed VLP-based ELISA were found to be highly concordant with those of a baculovirus-expressed VLP-based ELISA (r = 0.96 and 0.97 for HPV-16 and HPV-18) when detecing HPV vaccine induced antibodies and the concordance was medium (r = 0.68 and 0.68 for HPV-16 and HPV-18) when assessing natural infection induced antibodies. The results of the E. coli expressed VLP-based ELISA correlated well with those of the PBNA when testing 1020 post-vaccination human sera collected at one month after vaccination with the E. coli expressed VLP-based bivalent HPV vaccine (r = 0.83 and 0.81 for HPV-16 and HPV-18). The agreement and correlation were moderate (kappa<0.3 for both HPV types 16 and 18, r = 0.59 and 0.68 for HPV-16 and HPV-18, respectively) when assessing 1600 serum samples from unvaccinated women of age 18-25 years. In conclusion, the VLP-based ELISA is an acceptable surrogate for the neutralizing antibody assay in measuring vaccine responses. However, the use of the VLP-based ELISA in epidemiological studies should be carefully considered.

BMSCs reduce rat granulosa cell apoptosis induced by cisplatin and perimenopause.

BACKGROUND: The objective of this study was to evaluate the effect of bone marrow mesenchymal stem cells (BMSCs) on the apoptosis of granulosa cells (GCs) in rats. RESULTS: Cisplatin increased GC apoptosis from 0.59% to 13.04% in the control and cisplatin treatment groups, respectively, which was significantly reduced upon co-culture with BMSCs to 4.84%. Cisplatin treatment increased p21 and bax and decreased c-myc mRNA expression, which was reversed upon co-culture with BMSCs. As compared to young rats, increased apoptosis was observed in the perimenopausal rats (P < 0.001). After 3 months, the apoptosis rate in the BMSC group was significantly lower than that of the control group (P = 0.007). CONCLUSIONS: BMSC therapy may protect against GC apoptosis induced by cisplatin and perimenopause. Further studies are necessary to evaluate therapeutic efficacy of BMSCs.

Study of oxygen effects on electrochemiluminescence using dye-doped oxygen-resisting nanobeads.

Tris(4,7-diphenyl-1,10-phenanthroline)-ruthenium(II) (Rudpp) doped oxygen-resisting nanobeads were synthesized and applied in order to study the effects of oxygen on electrochemiluminescence.

Encoding electrochemiluminescence using Ru(bpy)3(2+) and fluorescein isothiocyanate co-doped silica nanoparticles.

In this paper, an electrochemiluminescence (ECL) encoding method was developed for the first time, based on a dual-dye system including Ru(bpy)(3)(2+) as an ECL emitter and fluorescein isothiocyanate (FITC) as a coding dye.