BACKGROUND: Cervical cancer and its precursor lesions are caused by a persistent high-risk human papillomavirus (hrHPV) infection. hrHPV testing has been reported to have higher sensitivity than Papanicolaou (Pap) testing for the detection of cervical precursor lesions. However, limited data are available for prior human papillomavirus (HPV) testing results for patients later diagnosed with invasive cervical cancer, especially in countries lacking a national cervical cancer screening program such as China. This study investigated prior hrHPV testing results for patients with invasive cervical cancer in China. METHODS: Cases with a histologic diagnosis of invasive cervical carcinoma were retrieved from Guangzhou KingMed Diagnostics (the largest independent pathology laboratory in China); prior hrHPV and Pap test results obtained within the year before the cancer diagnosis were recorded. RESULTS: HPV testing was negative in 7.5% of 427 cases of invasive cervical carcinoma, including squamous cell carcinoma (5%) and adenocarcinoma (25%). In 155 cervical cancer cases with prior hrHPV and Pap testing, the negative rate for Pap testing was 1.9%, and the negative rate for HPV was 9.7%. Furthermore, when only cases of adenocarcinoma (n 5 18) were examined, both the hrHPV-negative rate and the Pap-negative rate were higher at 33% and 5.6%, respectively. CONCLUSIONS: These data demonstrate a considerable prior hrHPV-negative rate and a lower prior Papnegative rate in patients with invasive cervical carcinoma (especially adenocarcinoma) from a population of women without access to an established screening program. Cancer (Cancer Cytopathol) 2015;123:428-34.

Background:Telepathology is increasingly being employed to support diagnostic consultation services. Prior publications have addressed technology aspects for telepathology, whereas this paper will address the clinical telepathology experience of KingMed Diagnostics, the largest independent pathology medical laboratory in China. Beginning in 2012 the University of Pittsburgh Medical Center (UPMC) and KingMed Diagnostics partnered to establish an international telepathology consultation service.Materials and Methods:This is a retrospective study that summarizes the telepathology experience and diagnostic consultation results between UPMC and KingMed over a period of 3 years from January 2012 to December 2014.Results:A total of 1561 cases were submitted for telepathology consultation including 144 cases in 2012, 614 cases in 2013, and 803 in 2014. Most of the cases (61.4%) submitted were referred by pathologists, 36.9% by clinicians, and 1.7% by patients in China. Hematopathology received the most cases (23.7%), followed by bone/soft tissue (21.0%) and gynecologic/breast (20.2%) subspecialties. Average turnaround time (TAT) per case was 5.4 days, which decreased from 6.8 days in 2012 to 5.0 days in 2014. Immunostains were required for most of the cases. For some difficult cases, more than one round of immunostains was needed, which extended the TAT. Among 855 cases (54.7%) where a primary diagnosis or impression was provided by the referring local hospitals in China, the final diagnoses rendered by UPMC pathologists were identical in 25.6% of cases and significantly modified (treatment plan altered) in 50.8% of cases.Conclusion:These results indicate that international telepathology consultation can significantly improve patient care by facilitating access to pathology expertise. The success of this international digital consultation service was dependent on strong commitment and support from leadership, information technology expertise, and dedicated pathologists who understood the language and culture on both sides. Lack of clinical information, missing gross pathology descriptions, and insufficient tissue sections submitted for evaluation were the main reasons for indefinite diagnoses. The overall experience encourages international telepathology practice for second opinions.

ObjectivesOsteoarthritis (OA) is the most common joint disease; however, the indeterminate nature of mechanisms by which OA develops has restrained advancement of therapeutic targets. TNF signalling has been implicated in the pathogenesis of OA. TNFR1 primarily mediates inflammation, whereas emerging evidences demonstrate that TNFR2 plays an anti-inflammatory and protective role in several diseases and conditions. This study aims to decipher TNFR2 signalling in chondrocytes and OA.MethodsBiochemical copurification and proteomics screen were performed to isolate the intracellular cofactors of TNFR2 complex. Bulk and single cell RNA-seq were employed to determine 14-3-3 epsilon (14-3-3ε) expression in human normal and OA cartilage. Transcription factor activity screen was used to isolate the transcription factors downstream of TNFR2/14-3-3ε. Various cell-based assays and genetically modified mice with naturally occurring and surgically induced OA were performed to examine the importance of this pathway in chondrocytes and OA.ResultsSignalling molecule 14-3-3ε was identified as an intracellular component of TNFR2 complexes in chondrocytes in response to progranulin (PGRN), a growth factor known to protect against OA primarily through activating TNFR2. 14-3-3ε was downregulated in OA and its deficiency deteriorated OA. 14-3-3ε was required for PGRN regulation of chondrocyte metabolism. In addition, both global and chondrocyte-specific deletion of 14-3-3ε largely abolished PGRN’s therapeutic effects against OA. Furthermore, PGRN/TNFR2/14-3-3ε signalled through activating extracellular signal-regulated kinase (ERK)-dependent Elk-1 while suppressing nuclear factor kappa B (NF-κB) in chondrocytes.ConclusionsThis study identifies 14-3-3ε as an inducible component of TNFR2 receptor complex in response to PGRN in chondrocytes and presents a previously unrecognised TNFR2 pathway in the pathogenesis of OA.

Our findings demonstrate that negative hrHPV testing on cervicovaginal cytology specimens in women later diagnosed with cervical carcinoma can be explained by the occurrence of truly HPV-negative carcinomas in more than half of patients. These results should be considered in the development of future cervical cancer screening guidelines.

Human respiratory syncytial virus (RSV) is a major viral pathogen of the lower respiratory tract of infants and young children worldwide. No effective prevention measure is available. Attenuated Salmonella strains expressing heterologous antigens can be delivered by the oral route, triggering efficient antigen-specific humoral, cellular, and mucosal immunity. In this study, we orally administered attenuated Salmonella strain SL7207, carrying the plasmid pcDNA3.1/F expressing the RSV F gene, to BALB/c mice and showed significant elevations of serum anti-RSV IgG and bronchoalveolar lavage secretory IgA as compared with the control group carrying empty plasmid (p<0.001). The ratio of IgG1 and IgG2a was 0.96. The experimental group also showed a stronger cytotoxic T cell response (p<0.01 at effector:target ratios of 100:1 and 50:1) and a higher stimulation index value of T cell proliferation (p<0.05) than the respective control group. RSV titers in the lung homogenates of the experimental group on day 3 and day 5 postchallenge were lower than in the control group (p<0.05). Histopathological analysis showed obvious differences in infiltration of inflammatory cells and pulmonary alveolar wall thickness (p<0.01) between the two groups. In summary, our results demonstrate the potential of orally administered SL7207-based DNA vaccines against RSV infection.