Vascular clips for preventing lymphocele and symptomatic lymphocele in patients with gynecologic malignancies after laparoscopic pelvic lymphadenectomy.

STUDY OBJECTIVE: To evaluate the effectiveness of using vascular clips to seal targeted lymphatics in gynecological malignancies for the prevention of postoperative pelvic lymphocele and symptomatic lymphocele after laparoscopic pelvic lymphadenectomy. DESIGN: Retrospective analysis. SETTING: Single-center academic hospital. PATIENTS: In total, 217 patients with gynecological malignancies were included. INTERVENTIONS: Patients were classified into two groups: group 1 (vascular clips were used to seal the targeted lymphatics) and group 2 (electrothermal instruments were used to seal the targeted lymphatics). The patients were followed up 4-6 weeks after surgery to evaluate the incidence of lymphoceles by ultrasound or CT. Symptomatic lymphoceles are defined as those that cause infection, deep vein thrombosis with or without swelling of the extremities, edema (swelling) of the extremities or perineum, hydronephrosis and/or moderate to severe pain. MEASUREMENT AND MAIN RESULTS: One hundred and thirteen patients were enrolled in group 1, and 104 patients were enrolled in group 2. Lymphoceles were observed in 46 (21.2%) patients. Fewer lymphoceles occurred in group 1 than in group 2 [8 (7.1%) vs. 38 (36.5%), p < 0.001]. The percentage of significantly sized lymphoceles was lower in group 1 than that in group 2 [4 (3.5%) vs. 30 (28.8%), p < 0.001]. Symptomatic lymphoceles occurred in 18 patients (8.3%), and only one (1.0%) occurred in group 1, while 17 (16.3%) occurred in group 2 (p < 0.001). A multivariate analysis revealed that vascular clips were the only independent factor for preventing lymphocele (OR = 7.65, 95% CI = [3.30, 17.13], p < 0.001) and symptomatic lymphocele (OR = 22.03, 95% CI = [2.84, 170.63], p = 0.003). CONCLUSIONS: The results indicate that the use of vascular clips may be useful for the prevention of the development of lymphocele and symptomatic lymphocele secondary to pelvic lymphadenectomy performed via laparoscopy.

Survival outcomes of abdominal radical hysterectomy, laparoscopic radical hysterectomy, robot-assisted radical hysterectomy and vaginal radical hysterectomy approaches for early-stage cervical cancer: a retrospective study.

BACKGROUND: This study compared the survival outcomes of abdominal radical hysterectomy (ARH) (N = 32), laparoscopic radical hysterectomy (LRH) (N = 61), robot-assisted radical hysterectomy (RRH) (N = 100) and vaginal radical hysterectomy (VRH) (N = 45) approaches for early-stage cervical cancer to identify the surgical approach that provides the best survival. METHODS: Disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method, and survival curves were compared using the log-rank test. RESULTS: The volume of intraoperative blood loss was greater in the ARH group than in the LRH group, the RRH group or the VRH group [(712.50 ± 407.59) vs. (224.43 ± 191.89), (109.80 ± 92.98) and (216.67 ± 176.78) ml, respectively; P < 0.001]. Total 5-year OS was significantly different among the four groups (ARH, 96.88%; LRH, 82.45%; RRH, 94.18%; VRH, 91.49%; P = 0.015). However, no significant difference in 5-year DFS was observed among the four groups (ARH, 96.88%; LRH, 81.99%; RRH, 91.38%; VRH, 87.27%; P = 0.061). CONCLUSION: This retrospective study demonstrated that ARH and RRH achieved higher 5-year OS rates than LRH for early-stage cervical cancer.

Prevalence characteristics of single and multiple HPV infections in women with cervical cancer and precancerous lesions in Beijing, China.

We assessed the prevalence characteristics of single and multiple high-risk human papillomavirus (HR-HPV) infections. A total of 1783 women who underwent colposcopy and cervical biopsy for abnormal ThinPrep Cytology Test and/or HR-HPV subtype genotyping results were enrolled in the study. Among the participants, 770 were diagnosed with cervicitis, 395 with cervical intraepithelial neoplasia grade 1 (CIN1), 542 with CIN2-3, and 76 with squamous cell carcinoma (SCC), with HR-HPV infection rates of 75.8%, 85.8%, 95.9%, and 88.4%, respectively. The prevalence of total and multiple HR-HPV infections exhibited a bimodal age distribution with a peak at ≤25 years, a decline with age and a second peak at ≥55 years, whereas single HR-HPV infections exhibited one peak from 35 to 44 years. The four most dominant HPV genotypes were HPV 16 (29.5%), 52 (15.0%), 58 (14.2%), and 18 (10.4%). In total, 67.0%, 70.4%, and 82.1% of patients with CIN1, CIN2-3, and SCC, respectively, had a single HR-HPV infection, which increased significantly with the aggravation of the cervical lesion grade (P = 0.045). Patients with a single HPV 16 infection had higher incidences of CIN2+ (62.2%) than those with multiple HPV 16 infections (52.4%) (P = 0.021). Patients coinfected with HPV 16 had higher CIN2+ incidence than those with single HPV 52, 31, 33, 35, 39, 45, 51, 56, or 59 infections (P < 0.001). This study provided baseline data on the prevalence characteristics of single and multiple HR-HPV infections in women attending a gynecological outpatient clinic in Beijing.

Effect of Mst1 on Endometriosis Apoptosis and Migration: Role of Drp1-Related Mitochondrial Fission and Parkin-Required Mitophagy.

BACKGROUND/AIMS: Mitochondrial homeostasis is implicated in the development and progression of endometriosis through poorly defined mechanisms. Mst1 is the major growth suppressor related to cancer migration, apoptosis and proliferation. However, whether Mst1 is involved in endometriosis apoptosis and migration via regulating the mitochondrial function remains to be elucidated. METHODS: Expression of Mst1 in endometriosis was examined via western blots. Cellular apoptosis was detected via MTT and TUNEL assay. Gain of function assay about Mst1 was conducted via adenovirus over-expression. Mitochondrial functions were evaluated via mitochondrial membrane potential JC-1 staining, ROS flow cytometry analysis, mPTP opening assessment and immunofluorescence of HtrA2/Omi. The mitophagy activity were examined via western blots and immunofluorescence. RESULTS: First, we found that Mst1 was significantly downregulated in the ectopic endometrium of endometriosis compared to the normal endometrium. However, the recovery of Mst1 function was closely associated with the inability of endometrial stromal cells (ESCs) to migrate and survive. A functional study indicated that regaining Mst1 enhanced Drp1 post-transcriptional phosphorylation at Ser616 and repressed Parkin transcription activity via p53, leading to mitochondrial fission activation and mitophagy inhibition. Excessive Drp1-related fission forced the mitochondria to liberate HtrA2/Omi into the cytoplasm. Moreover, Mst1-induced defective mitophagy evoked cellular oxidative stress, energy metabolism and calcium overload. Through excessive mitochondrial fission and aberrant mitophagy, Mst1 launched caspase 9-related mitochondrial apoptosis and abrogated F-actin/lamellipodium-dependent cellular migration. Notably, we also defined NR4A/miR181c as the upstream signal for Mst1 dysfunction in endometriosis. CONCLUSION: Collectively, our results comprehensively described the important role of the NR4A-miR181c-Mst1 pathway in endometriosis, which handled mitochondrial apoptosis and F-actin/ lamellipodium-based migration via the regulation of Drp1-related mitochondrial fission and Parkin-required mitophagy, with a potential application in endometriosis therapy by limiting ESCs migration and promoting apoptosis.

Integration analysis of microRNA and mRNA paired expression profiling identifies deregulated microRNA-transcription factor-gene regulatory networks in ovarian endometriosis.

BACKGROUND: The etiology and pathophysiology of endometriosis remain unclear. Accumulating evidence suggests that aberrant microRNA (miRNA) and transcription factor (TF) expression may be involved in the pathogenesis and development of endometriosis. This study therefore aims to survey the key miRNAs, TFs and genes and further understand the mechanism of endometriosis. METHODS: Paired expression profiling of miRNA and mRNA in ectopic endometria compared with eutopic endometria were determined by high-throughput sequencing techniques in eight patients with ovarian endometriosis. Binary interactions and circuits among the miRNAs, TFs, and corresponding genes were identified by the Pearson correlation coefficients. miRNA-TF-gene regulatory networks were constructed using bioinformatic methods. Eleven selected miRNAs and TFs were validated by quantitative reverse transcription-polymerase chain reaction in 22 patients. RESULTS: Overall, 107 differentially expressed miRNAs and 6112 differentially expressed mRNAs were identified by comparing the sequencing of the ectopic endometrium group and the eutopic endometrium group. The miRNA-TF-gene regulatory network consists of 22 miRNAs, 12 TFs and 430 corresponding genes. Specifically, some key regulators from the miR-449 and miR-34b/c cluster, miR-200 family, miR-106a-363 cluster, miR-182/183, FOX family, GATA family, and E2F family as well as CEBPA, SOX9 and HNF4A were suggested to play vital regulatory roles in the pathogenesis of endometriosis. CONCLUSION: Integration analysis of the miRNA and mRNA expression profiles presents a unique insight into the regulatory network of this enigmatic disorder and possibly provides clues regarding replacement therapy for endometriosis.

Association between oestrogen receptor alpha (ESR1) gene polymorphisms and endometriosis: a meta-analysis of 24 case-control studies.

The PvuII (C > T), XbaI (A > G) and (TA)n polymorphisms of ESR1 gene are potentially associated with susceptibility to endometriosis. A meta-analysis was conducted to evaluate comprehensively the associations between endometriosis and ESR1 polymorphisms. Twenty-four studies, including 2740 cases and 3208 controls, were retrieved through searches of PubMed, EMBASE, Web of Science, CBM and CNKI. Meta-analyses showed that PvuII was associated with endometriosis only for stage I-III, only under a recessive model (OR = 1.53, 95% CI 1.05 to 2.21; P = 0.025). The short allele and TA13 of (TA)n were associated with a higher risk of endometriosis (ORS = 1.71, 95% CI 1.01 to 2.81, P = 0.046; ORTA13 = 1.45, 95% CI 1.06 to 1.97, PTA13 = 0.019); TA20 repeats was associated with a lower risk (OR = 0.36, 95% CI 0.16 to 0.80; P = 0.012). No statistically significant association was found in the XbaI polymorphism. This meta-analysis indicated that the PvuII and XbaI polymorphisms were not associated with the risk of endometriosis, whereas stage classification of endometriosis was likely to influence the association of PvuII polymorphism. The (TA)n polymorphisms might play roles in the susceptibility to, or protection against, the pathogenesis of endometriosis.

The prognostic value and clinicopathological significance of CD44 expression in ovarian cancer: a meta-analysis.

PURPOSE: The prognostic value and clinicopathological significance of CD44 in ovarian cancer (OC) remain unclear. This meta-analysis, therefore, aims to evaluate the correlation between CD44 expression and OC. METHODS: Studies published until March 2016 were searched in PubMed, EMBASE, and ISI Web of Knowledge databases. The odds ratio (OR) and the hazard ratio (HR) with 95 % confidence interval (CI) were used to assess the effects. RESULTS: Twenty-four studies that include 2267 OC patients were identified for the final analysis. Sixteen studies investigated the expression difference of CD44 standard (CD44s) in 1848 patients. Results showed that high CD44s expression is associated with chemoresistance (OR 5.94, 95 % CI 1.91-18.47) and short disease-free survival (DFS) time (HR 2.57, 95 % CI 1.34-4.91). In addition, CD44s expression is not associated with tumor differentiation grade, residual mass, lymphoid nodal metastasis, and overall survival (OS). Ten studies investigated the expression difference of CD44v6 in 724 patients. Results showed that the CD44v6 expression is not correlated with FIGO stage, tumor differentiation grade, lymphoid nodal metastasis, and OS. CONCLUSION: High CD44s expression possibly indicates poor prognosis in OC patients given that high CD44s expression initiates chemotherapy resistance, although this expression pattern is not an independent predictive factor for OS. Meanwhile, high CD44s expression may be related to poor DFS of OC, but this relationship must be further confirmed. In addition, the result in which CD44v6 is not associated with OS of OC patients should be interpreted with caution.

ARHI overexpression induces epithelial ovarian cancer cell apoptosis and excessive autophagy.

OBJECTIVE: ARHI is a maternally imprinted tumor suppressor gene that is responsible for initiating programmed cell death and inhibiting cancer cell growth. However, the influence of ARHI on epithelial ovarian cancer cell death and the underlying mechanisms behind how ARHI regulates cancer cells still require further studies. METHODS: Epithelial ovarian cancer cells TOV112D and ES-2 were used in this in vitro study. Cell proliferation, apoptosis, and autophagy activities were compared in TOV112D and ES-2 cells transfected with ARHI vectors or control vectors. Bcl-2 siRNA was transfected into TOV112D cells to investigate the roles of Bcl-2 played in regulating apoptosis and autophagy. RESULTS: ARHI expression was reduced in TOV112D and ES-2 cells compared with normal epithelial ovarian cells (NOE095 and HOSEpiC). Overexpressed ARHI inhibited cancer cell proliferation, whereas induced forced cell apoptosis and excessive formation of autophagosomes inhibited promoted cell death. Furthermore, we found that Bcl-2 expression moderately declined in response to ARHI overexpressing in ES-2 and TOV112D cells; meanwhile, more apoptotic cells and higher LC3 level presented after silence of Bcl-2 in TOV112D cells. Reduced Bcl-2-Beclin 1 complex were observed in ARHI overexpressing cells. Moreover, modulation of ARHI to Bcl-2 expression could be ascribed partially to the activation of PI3k/AKT pathway. The addition of LY294002 enabled to suppress Bcl-2 expression and cell proliferation. CONCLUSIONS: The silence of ARHI expression in vitro seems to accelerate the malignant transformation of healthy ovarian cells by restraining apoptosis and autophagy. The overexpressed ARHI in TOV112D cancer cells suppresses the activation of PI3K/AKT and reduces the expression of Bcl-2, leading to enhanced cell apoptosis and autophagic cancer cell death.

Complete genome sequences of two Chinese virulent avian coronavirus infectious bronchitis virus variants.

Avian coronavirus infectious bronchitis virus (IBV) is variable, which causes many serotypes. Here we reported the complete genome sequences of two virulent IBV variants from China, GX-YL5 and GX-YL9, belonging to different serotypes. Differences between GX-YL5 and GX-YL9 were found mainly in stem-loop structure I in the predicted RNA secondary structure of open reading frame (ORF) 1b and the S protein gene fusion region, which will help us understand the molecular evolutionary mechanism of IBV and the disconcordance between the genotypes and serotypes of coronavirus.

Continuous evolution of avian infectious bronchitis virus resulting in different variants co-circulating in Southern China.

Sixty field strains of avian infectious bronchitis virus (IBV) were isolated from chicken flocks in different regions of Guangxi from 1985 to 2012. Phylogenetic analysis of S1 subunit glycoprotein genes revealed that field isolates from 2009-2011 mostly belonged to the LX4 type, while those from 1985-2008 belonged to the HN08 type, and a few others belonged to the 4/91 type, the TW type and the Mass type. In addition, it is noteworthy that no obvious regional differences were found among these 60 strains isolated from six regions in Guangxi, while there was a high degree of sequence identity among the isolates in the same period of time.

A pan-sharpening network using multi-resolution transformer and two-stage feature fusion.

Pan-sharpening is a fundamental and crucial task in the remote sensing image processing field, which generates a high-resolution multi-spectral image by fusing a low-resolution multi-spectral image and a high-resolution panchromatic image. Recently, deep learning techniques have shown competitive results in pan-sharpening. However, diverse features in the multi-spectral and panchromatic images are not fully extracted and exploited in existing deep learning methods, which leads to information loss in the pan-sharpening process. To solve this problem, a novel pan-sharpening method based on multi-resolution transformer and two-stage feature fusion is proposed in this article. Specifically, a transformer-based multi-resolution feature extractor is designed to extract diverse image features. Then, to fully exploit features with different content and characteristics, a two-stage feature fusion strategy is adopted. In the first stage, a multi-resolution fusion module is proposed to fuse multi-spectral and panchromatic features at each scale. In the second stage, a shallow-deep fusion module is proposed to fuse shallow and deep features for detail generation. Experiments over QuickBird and WorldView-3 datasets demonstrate that the proposed method outperforms current state-of-the-art approaches visually and quantitatively with fewer parameters. Moreover, the ablation study and feature map analysis also prove the effectiveness of the transformer-based multi-resolution feature extractor and the two-stage fusion scheme.

Robotic-Assisted Laparoscopic Sacrocolpopexy for Pelvic Organ Prolapse: A Single Center Experience in China.

OBJECTIVE: The aim is to investigate the efficiency and outcome of robotic-assisted sacrocolpopexy (RASC) in a cohort of patients with pelvic organ prolapse (POP) in our Gynecology Department. METHODS: We performed a retrospective study of female patients who underwent RASC in Chinese PLA General Hospital from January 2013 to December 2020. Their clinical features included age, degree of prolapse, menopause time, body mass index, pregnancy, delivery, operation time, and bleeding volume. All patients were followed up for more than 6 months. POP-Q was recorded to evaluate the position of prolapsed organs. PFDI-20, PFIQ-7, and PGI-I were used to evaluate the life quality after surgery. RESULTS: Twenty-four patients with POP received RASC in our center. The intraoperative bleeding was 86.9 ± 98.3 ml (20-300 ml). The operation time was 143.5 ± 47.3 min (60-240 minutes). The hospitalization time was 10.4 ± 2.1 days (8-16 days). And the follow-up time was 40.8 ± 22.0 months (6-72 months). In the POP-Q follow-up, postoperative Aa, Ba, Ap, Bp, and C were significantly improved than those before surgery (P < 0.05). The objective and subjective cure rate was 100%. PGI-I score was very good in 9 (9/24), very good in 10 (10/24), and good in 3 (3/24). Postoperative PFDI-20 and PFIQ-7 were 2.78 ± 3.82 and 1.57 ± 3.86, which decreased dramatically after surgery (P < 0.05). Mesh exposure occurred in 4 cases (16.7%) at 2-12 months. The exposed diameters were less than 1 cm in 3 cases (2 A/T3/S1) and 1-2 cm in 1 case (3 B/T3/S1). These mesh exposures healed after conservative observation or mesh excision. CONCLUSION: RASC for POP has the advantage of less bleeding and hospitalization time. It is a minimally invasive option for pelvic organ prolapse.

Phylogenetic and Spatiotemporal Analyses of the Complete Genome Sequences of Avian Coronavirus Infectious Bronchitis Virus in China During 1985-2020: Revealing Coexistence of Multiple Transmission Chains and the Origin of LX4-Type Virus.

Infectious bronchitis (IB) virus (IBV) causes considerable economic losses to poultry production. The data on transmission dynamics of IBV in China are limited. The complete genome sequences of 212 IBV isolates in China during 1985-2020 were analyzed as well as the characteristics of the phylogenetic tree, recombination events, dN/dS ratios, temporal dynamics, and phylogeographic relationships. The LX4 type (GI-19) was found to have the highest dN/dS ratios and has been the most dominant genotype since 1999, and the Taiwan-I type (GI-7) and New type (GVI-1) showed an increasing trend. A total of 59 recombinants were identified, multiple recombination events between the field and vaccine strains were found in 24 isolates, and the 4/91-type (GI-13) isolates were found to be more prone to being involved in the recombination. Bayesian phylogeographic analyses indicated that the Chinese IBVs originated from Liaoning province in the early 1900s. The LX4-type viruses were traced back to Liaoning province in the late 1950s and had multiple transmission routes in China and two major transmission routes in the world. Viral phylogeography identified three spread regions for IBVs (including LX4 type) in China: Northeastern China (Heilongjiang, Liaoning, and Jilin), north and central China (Beijing, Hebei, Shanxi, Shandong, and Jiangsu), and Southern China (Guangxi and Guangdong). Shandong has been the epidemiological center of IBVs (including LX4 type) in China. Overall, our study highlighted the reasons why the LX4-type viruses had become the dominant genotype and its origin and transmission routes, providing more targeted strategies for the prevention and control of IB in China.

Exploring the Potential Key IncRNAs with Endometriosis by Construction of a ceRNA Network.

PURPOSE: The etiology and pathophysiology of endometriosis remain unclear. Current research indicates long noncoding RNA (lncRNA) may play an important role in the pathogenesis and development of endometriosis. However, the molecular mechanism of lncRNA in endometriosis is far from clear. PATIENTS AND METHODS: The lncRNA and mRNA expression of 8 patients with ovarian endometriosis were determined by high-throughput RNA sequencing (8 ectopic endometria samples vs 8 eutopic endometria samples), and miRNA expression profiles were obtained from our previous study. Then a lncRNA-associated competing endogenous RNA (ceRNA) network was constructed by combining the regulatory interaction and negative co-expression interaction between the differentially expressed lncRNAs/mRNAs and miRNAs by different rules. RESULTS: The constructed lncRNA-related ceRNA network was composed of two separate networks, network 1 including 14,137 dysregulated lncRNA-mRNA interactions, referring to 242 lncRNAs, 55 miRNAs and 1600 mRNAs, network 2 including 4459 dysregulated lncRNA-mRNA interactions, referring to 111 lncRNAs, 39 miRNAs and 1151 mRNAs. The top six hub lncRNAs (LINC01140, MSC-AS1, HAGLR, CKMT2-AS1, JAKMIP2-AS1, AL365361.1) in the significant ternary relationship of mRNA-miRNA-lncRNA in network 1, and the top six hub lncRNAs (PAX8-AS1, MIR17HC, PART1, HOXA-AS3, PLAC4, LINC00511) in the significant ternary relationship of mRNA-miRNA-lncRNA in network 2 were selected. Functional enrichment analysis of these lncRNA-related mRNAs indicated that the lncRNAs in network 1 mainly take part in positive regulation of phagocytosis, myeloid leukocyte activation, and tissue remodeling, while the lncRNAs in network 2 mainly take part in negative regulation of cell proliferation, blood vessel development and regulation of epithelial cell differentiation, which is consistent with the results obtained from the different rules to construct the networks. CONCLUSION: lncRNA-related ceRNA network analysis recognized key lncRNAs related to the development of endometriosis.

Identification of a novel avian coronavirus infectious bronchitis virus variant with three-nucleotide-deletion in nucleocapsid gene in China.

A novel avian infectious bronchitis virus (IBV) variant, designated as GX-NN160421, was isolated from vaccinated chicken in Guangxi, China, in 2016. Based on analysis of the S1 gene sequence, GX-NN160421 belonged to the New-type 1 (GVI-1) strain. More importantly, three consecutive nucleotides (AAC) deletions were found in the highly conserved structure gene N. The serotype of GX-NN160421 was different from those of the commonly used vaccine strains. The mortality of the GX-NN160421 strain was 3.33%, which contrasted with 50% mortality in the clinical case, but high levels of virus shedding lasted at least 21 days. In conclusion, the first novel IBV variant with three-nucleotide-deletion in the N gene was identified, and this unique variant is low virulent but with a long time of virus shedding, indicating the continuing evolution of IBV and emphasizing the importance of limiting exposure to novel IBV strains as well as extensive monitoring of new IBVs.

Mortality and Attrition Rates within the First Year of Antiretroviral Therapy Initiation among People Living with HIV in Guangxi, China: An Observational Cohort Study.

OBJECTIVE: To assess the mortality and attrition rates within the first year of antiretroviral therapy (ART) initiation among people living with human immunodeficiency virus (PLHIV) in rural Guangxi, China. DESIGN: Observational cohort study. Setting. The core treatment indicators and data were collected with standard and essential procedures as per the Free ART Manual guidelines across all the rural health care centers of Guangxi. Participants. 58,115 PLHIV who were under ART were included in the study. Interventions. The data collected included sociodemographic characteristics that consist of age, sex, marital status, route of HIV transmission, CD4 cell count before ART, initial ART regimen, level of ART site, and year of ART initiation. Primary and Secondary Outcome Measures. Mortality and attrition rate following ART initiation. RESULTS: The average mortality rate was 5.94 deaths, and 17.52 attritions per 100 person-years within the first year of ART initiation among PLHIV. The mortality rate was higher among intravenous drug users (Adjusted Hazard Ratio (AHR) 1.27, 95% Confidence Interval (CI) 1.14-1.43), prefecture as a level of ART site (AHR 1.14, 95% CI 1.02-1.28), and county as the level of ART site (AHR 2.12, 95% CI 1.90-2.37). Attrition was higher among intravenous drug users (AHR 1.87, 95% CI 1.75-2.00), the first-line ART containing AZT (AHR 1.09, 95% CI 1.03-1.16), and first-line ART containing LVP/r (AHR 1.34, 95% CI 1.23-1.46). CONCLUSION: The mortality and attrition rates were both at the highest level in the first year of post-ART; continued improvement in the quality of HIV treatment and care is needed.

Construction and Immunogenicity Comparison of Three Virus-Like Particles Carrying Different Combinations of Structural Proteins of Avian Coronavirus Infectious Bronchitis Virus.

Infectious bronchitis virus (IBV) poses massive economic losses in the global poultry industry. Here, we firstly report the construction and immunogenicity comparison of virus-like particles (VLPs) carrying the S, M and E proteins (SME-VLPs); VLPs carrying the S and M proteins (SM-VLPs); and VLPs carrying the M and E proteins (ME-VLPs) from the dominant serotype representative strain GX-YL5 in China. The neutralizing antibody response induced by the SME-VLPs was similar to that induced by the inactivated oil vaccine (OEV) of GX-YL5, and higher than those induced by the SM-VLPs, ME-VLPs and commercial live vaccine H120. More importantly, the SME-VLPs elicited higher percentages of CD4+ and CD8+ T lymphocytes than the SM-VLPs, ME-VLPs and OEV of GX-YL5. Compared with the OEV of GX-YL5, higher levels of IL-4 and IFN-γ were also induced by the SME-VLPs. Moreover, the mucosal immune response (sIgA) induced by the SME-VLPs in the tear and oral swabs was comparable to that induced by the H120 vaccine and higher than that induced by the OEV of GX-YL5. In the challenge experiment, the SME-VLPs resulted in significantly lower viral RNA levels in the trachea and higher protection scores than the OEV of GX-YL5 and H120 vaccines, and induced comparable viral RNA levels in the kidneys, and tear and oral swabs to the OEV of GX-YL5. In summary, among the three VLPs, the SME-VLPs carrying the S, M and E proteins of IBV could stimulate the strongest humoral, cellular and mucosal immune responses and provide effective protection, indicating that it would be an attractive vaccine candidate for IB.

Identification of MicroRNAs as Potential Biomarkers in Ovarian Endometriosis.

Endometriosis, as a prevalent gynecological disease, is characterized by the presence of endometrial-like tissue outside the uterus, causing infertility and considerable pain and affecting the quality of life of women. The pathogenic mechanism has not been fully elucidated, and there are no effective biomarkers for endometriosis. In our study, microRNA (miRNA) expression profiling of 10 ectopic endometrial plasma from patients with ovarian endometriosis and 10 normal plasma from healthy controls was analyzed using a microarray. As a result, 114 differentially expressed miRNAs were identified. Among them, 14 miRNAs were significantly downregulated in patients with ovarian endometriosis, which matched the microarray results. The diagnostic value of the 14 downregulated miRNAs in ovarian endometriosis was evaluated by receiver operating characteristic (ROC) curve analysis, and hsa-let-7i-5p showed the highest area under the ROC curve (AUC) with a value of 0.900. The target genes of the 14 miRNAs were predicted by miRWalk2.0, and the genes that were targeted by at least 2 of the 14 miRNAs were analyzed by function enrichment. The target genes were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, such as microRNAs in cancer, bladder cancer, and endocrine resistance pathways, and the Gene Ontology (GO) terms such as nucleobase-containing compound metabolic process, cellular nitrogen compound biosynthetic process, and heterocycle metabolic process. The identified 14 differentially expressed miRNAs could be potential biomarkers and therapeutic targets for the diagnosis and treatment of endometriosis.

Cervical cancer evaluated with integrated 18F-FDG PET/MR.

The current study aimed to evaluate the correlation between maximum standardized uptake value (SUVmax) and minimum apparent diffusion coefficient (ADCmin) of cervical cancer using an integrated 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance (PET/MR) imaging system, and to determine the association with pathological prognostic factors. A total of 46 patients were pathologically diagnosed with cervical cancer and underwent PET/MR prior to surgery, including total hysterectomy, bilateral pelvic lymph node dissection or paraaortic lymph node dissection. The imaging biomarkers included the SUVmax and ADCmin. The pathological prognostic factors were as follows: Tumor size, histological grade, International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis. Pearson's correlation analysis was used to evaluate the correlation between imaging biomarkers and the tumor size and the Mann-Whitney U test analysis was used to evaluate the association between imaging biomarkers and pathological factors. The mean SUVmax was 11.1±8.7 (range, 3.16-51.6) and the mean ADCmin was 0.76±0.15×10-3 mm2/s (range, 0.47-1.04×10-3 mm2/s). The SUVmax had a significant negative correlation with the ADCmin (r=-0.700; P<0.001). The SUVmax was significantly increased in patients with poorly differentiated tumors (P=0.001), patients with FIGO stage IIB (P=0.005) and the patients with lymph node metastasis (P=0.040). The ADCmin was significantly decreased in patients with poorly differentiated tumors (P<0.001) and patients with FIGO stage IIB (P=0.017). Statistical analysis revealed no significant correlation between the tumor size and the SUVmax (r=0.286;P=0.054), or between the tumor size and the ADCmin (r=-0.231; P=0.122). Area under the curve (AUC) analysis revealed that SUVmax had a higher diagnostic value for lymph node metastasis (AUC=0.681) and FIGO staging (AUC=0.837) compared with ADCmin, whereas ADCmin had a higher diagnostic value for the grade of pathological differentiation (AUC=0.816) compared with SUVmax (AUC=0.788). The results of the current study demonstrated that there was a significant negative correlation between SUVmax and ADCmin, which were associated with prognostic factors.

Genetic Analysis of Avian Coronavirus Infectious Bronchitis Virus in Yellow Chickens in Southern China over the Past Decade: Revealing the Changes of Genetic Diversity, Dominant Genotypes, and Selection Pressure.

The high mutation rates of infectious bronchitis virus (IBV) pose economic threats to the poultry industry. In order to track the genetic evolutionary of IBV isolates circulating in yellow chickens, we continued to conduct the genetic analyses of the structural genes S1, E, M, and N from 64 IBV isolates in southern China during 2009-2017. The results showed that the dominant genotypes based on the four genes had changed when compared with those during 1985-2008. Based on the S1 gene phylogenetic tree, LX4-type (GI-19) was the most dominant genotype, which was different from that during 1985-2008. The second most dominant genotype was LDT3-A-type, but this genotype disappeared after 2012. New-type 1 (GVI-1) isolates showed increasing tendency and there were four aa (QKEP) located in the hypervariable region (HVR) III and one aa (S) insertion in all the New-type 1 isolates. Both the analyses of amino acid entropy and molecular evolutionary rate revealed that the variations from large to small were S1, E, M, and N. Purifying selection was detected in the S1, E, M, and N gene proteins, which was different from the positive selection during 1985-2008. Six isolates were confirmed to be recombinants, possibly generated from a vaccine virus of the 4/91-type or LDT3-A-type and a circulating virus. The estimated times for the most recent common ancestors based on the S1, E, M, and N genes were the years of 1744, 1893, 1940, and 1945, respectively. Bayesian skyline analysis revealed a sharp decrease in genetic diversity of all the four structural genes after 2010 and since late 2015, the viral population rapidly rose. In conclusion, the IBVs circulating in southern China over the past decade have experienced a remarkable change in genetic diversity, dominant genotypes, and selection pressure, indicating the importance of permanent monitoring of circulating strains and the urgency for developing new vaccines to counteract the emerging LX4-type and New-type IBVs.