Objective:To evaluate the 10-year protective effect and immunogenicity of quadrivalent human papillomavirus (HPV) vaccine in Chinese women aged 20 to 45 years.Methods:From October 2019 to April 2020, a long-term follow-up study was conducted on the subjects of the Phase III clinical trial of the quadrivalent HPV vaccine (NCT00834106). Participants underwent a questionnaire survey, venous blood sampling, gynecological examination, cervical exfoliated cell pathology examination, and serum neutralizing antibody titers for HPV-6, 11, 16, and 18 were measured using a pseudovirus neutralization assay. The results of the cytological examination and the positive rate and titers of serum antibodies of different cervical exfoliated cells were compared.Results:A total of 889 subjects were followed up, including 240 in the control group, 453 in the vaccination group and 196 in the post-trial vaccination group. The age of the control group was (40±7) years old, which was higher than that of the supplementary vaccination group and the vaccination group [(38±4) and (38±6) years old, respectively] ( P<0.05). There were no statistically significant differences in condom use and sexual frequency among all groups (all P values>0.05). The abnormal proportion of cervical exfoliation cytopathology in the vaccination group was 3.7% (17/453), which was significantly lower than that in the control group [9.6% (23/240)] and post-trial vaccination group [5.6% (11/196)] ( P<0.05). There were two cases of cervical intraepithelial neoplasia (CIN) grade 1 in the vaccination group, two cases of CIN grade 1 and three cases of CIN grade 2 and above in the control group, and no CIN grade 1 and above cases in the post-trial vaccination group. The positive rate of HPV-18 antibody was 35.5% (161/453) in the vaccination group and 76.0% (149/196) in the post-trial vaccination group, which was significantly lower than that of other types ( P<0.05). The neutralizing antibody GMT ratio between the vaccination group and the control group ranged from 2.62 to 25.33 (9.05 to 83.08). Conclusion:Protective neutralizing antibodies are sustained in Chinese women aged 20 to 45 years after ten years of vaccination with quadrivalent HPV vaccine.

Objective:To evaluate the 10-year protective effect and immunogenicity of quadrivalent human papillomavirus (HPV) vaccine in Chinese women aged 20 to 45 years.Methods:From October 2019 to April 2020, a long-term follow-up study was conducted on the subjects of the Phase III clinical trial of the quadrivalent HPV vaccine (NCT00834106). Participants underwent a questionnaire survey, venous blood sampling, gynecological examination, cervical exfoliated cell pathology examination, and serum neutralizing antibody titers for HPV-6, 11, 16, and 18 were measured using a pseudovirus neutralization assay. The results of the cytological examination and the positive rate and titers of serum antibodies of different cervical exfoliated cells were compared.Results:A total of 889 subjects were followed up, including 240 in the control group, 453 in the vaccination group and 196 in the post-trial vaccination group. The age of the control group was (40±7) years old, which was higher than that of the supplementary vaccination group and the vaccination group [(38±4) and (38±6) years old, respectively] ( P<0.05). There were no statistically significant differences in condom use and sexual frequency among all groups (all P values>0.05). The abnormal proportion of cervical exfoliation cytopathology in the vaccination group was 3.7% (17/453), which was significantly lower than that in the control group [9.6% (23/240)] and post-trial vaccination group [5.6% (11/196)] ( P<0.05). There were two cases of cervical intraepithelial neoplasia (CIN) grade 1 in the vaccination group, two cases of CIN grade 1 and three cases of CIN grade 2 and above in the control group, and no CIN grade 1 and above cases in the post-trial vaccination group. The positive rate of HPV-18 antibody was 35.5% (161/453) in the vaccination group and 76.0% (149/196) in the post-trial vaccination group, which was significantly lower than that of other types ( P<0.05). The neutralizing antibody GMT ratio between the vaccination group and the control group ranged from 2.62 to 25.33 (9.05 to 83.08). Conclusion:Protective neutralizing antibodies are sustained in Chinese women aged 20 to 45 years after ten years of vaccination with quadrivalent HPV vaccine.

A group of compounds structurally related to tetrahydrocannabinol or capable of binding to cannabinoid receptors are collectively referred to as cannabinoids. Cannabinoids can be divided into plant derived cannabinoids， synthetic cannabinoids， and endogenous cannabinoids. Δ-9-THC is the only psychoactive compound in plant cannabinoids. Cannabis with Δ-9-THC>0.3% is internationally listed as a prohibited drug， while cannabis with Δ-9-THC<0.3% is industrial cannabis. Due to its low addiction and high commercial value， it is allowed to be added to food in many countries. More and more industrial cannabis foods become popular， and the detection/analysis of cannabinoid compounds in cannabis foods is particularly important； In addition to industrial cannabis， which is widely used in food， there are also various new drugs， synthetic cannabinoids， disguised as conventional food， which can cause the social problems and increase the food safety risks. This article will elaborate on the regulatory status of cannabinoid compounds in food， In order to promote the safety supervision of the domestic cannabis food.

Membrane-disruptive peptides/peptidomimetics (MDPs) are antimicrobials or anticarcinogens that present a general killing mechanism through the physical disruption of cell membranes, in contrast to conventional chemotherapeutic drugs, which act on precise targets such as DNA or specific enzymes. Owing to their rapid action, broad-spectrum activity, and mechanisms of action that potentially hinder the development of resistance, MDPs have been increasingly considered as future therapeutics in the drug-resistant era. Recently, growing experimental evidence has demonstrated that MDPs can also be utilized as adjuvants to enhance the therapeutic effects of other agents. In this review, we evaluate the literature around the broad-spectrum antimicrobial properties and anticancer activity of MDPs, and summarize the current development and mechanisms of MDPs alone or in combination with other agents. Notably, this review highlights recent advances in the design of various MDP-based drug delivery systems that can improve the therapeutic effect of MDPs, minimize side effects, and promote the co-delivery of multiple chemotherapeutics, for more efficient antimicrobial and anticancer therapy.

Nanoparticles (NPs) have shown potential in cancer therapy, while a single administration conferring a satisfactory outcome is still unavailable. To address this issue, the dissolving microneedles (DMNs) were developed to locally deliver functionalized NPs with combined chemotherapy and photothermal therapy (PTT).

Circadian clock is an inherent biological rhythm of organism which forms in the long process of evolution to adapt to the changes in light and temperature due to day-night alternation. Circadian clock in humans is accurately regulated by various circadian clock genes at the molecular level and are hierarchically regulated by the central clock and the peripheral clock at the anatomical level. Recent studies have found that circadian clock genes can participate in intracellular lipid metabolism by regulating downstream clock-controlled genes, and the disorder of circadian clock genes can result in abnormal lipid metabolism, oxidative stress, insulin resistance, and abnormal secretion of glucocorticoids and inflammatory factors, which are closely associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The disorder of circadian clock genes can also increase the susceptibility to fatty liver disease and thus acts as a bridge that connects circadian clock genes and NAFLD. The pathogenesis of NAFLD remains unclear at present, and therefore, this article summarizes the recent studies on the association between circadian clock genes and NAFLD, so as to provide a theoretical basis for further clarifying the pathogenesis of NAFLD.

Objective: To investigate the imaging diagnosis, treatment and prognosis of primary hepatic neuroendocrine tumors. Methods: The clinical features, imaging manifestations, histopathological and immunohistochemical findings and interventional therapy of 6 patients identified with pathologically confirmed primary hepatic neuroendocrine tumors were retrospectively analyzed, and the related literatures were reviewed. Results: All 6 patients presented with symptoms of abdominal pain. 4 patients had solitary hepatic mass and 2 patients had multiple hepatic masses. Magnetic resonance imaging showed low signal intensity on T1 weighted imaging, high signal intensity on T2 weighted imaging and clear boundary; the arterial phase of enhancement scan was uneven and enhanced, and portal venous phase or delayed phase showed continuous enhancement, surrounded by ring enhanced capsule. A pathological diagnosis was primary neuroendocrine tumor of the liver. After interventional treatment, 6 patients had some therapeutic effects. Among them, 4 patients underwent multiple interventional therapies, followed by 4 years of follow-up has shown satisfactory results. Conclusion Primary hepatic neuroendocrine tumors are very rare and their imaging manifestations are specific. Eventually, relies on pathological and immunohistochemical diagnosis. Transarterial chemoembolization therapy can bring satisfactory results in the treatment of primary hepatic neuroendocrine tumor.

Objective: To evaluate and compare the screening performance of primary high-risk HPV(HR-HPV) screening and HR-HPV screening plus liquid-based cytology (LBC) cotesting in diagnosis of cervical cancer and precancerous lesions (CIN2+). Methods: We pooled 17 population-based cross-sectional studies which were conducted across China from 1999 to 2008. After obtaining informed consent, all women received liquid-based cytology(LBC)testing, HR-HPV DNA testing. Totally 28 777 women with complete LBC, HPV and biopsy results were included in the final analysis. Screening performance of primary HR-HPV DNA screening and HPV screening plus LBC co-testing in diagnosis of CIN2+ were calculated and compared among different age groups. Results: Among the whole population, the detection rates of primary HR-HPV screening and HR-HPV screening plus LBC co-testing are 3.05% (879 CIN2+) and 3.13%(900 CIN2+), respectively. The sensitivity were 96.4% and 98.7% (χ²=19.00, P<0.001), and the specificity were 86.2% and 78.8% (χ²=2 067.00, P<0.001), respectively. Areas under the receiver operating characteristic (ROC) curve (AUC) showed that the primary HR-HPV screening performed better than co-testing (AUC were 0.913 and 0.888; Z=6.16, P<0.001). Compared with primary HR-HPV screening, co-testing showed significantly higher colposcopy referral rates (16.5% and 23.6%, respectively, χ²=132.00, P<0.001) and the number of colposcopy examination for detecting per CIN2+ (5.4 and 7.6, respectively).In the group aged 25-29, the colposcopy referral rates was 8.7 (10.9%(199 cases) vs 1.3%(23 cases)) times as much as the detection rate of primary HR-HPV screening in diagnosis of CIN2+, and was 12.5 (15.7%(288 cases) vs 1.3%(23 cases)) times as much as the detection rate of HR-HPV screening plus cytology contesting. Conclusion Compared with primary HR-HPV screening, HR-HPV screening plus cytology co-testing does not show better results in the screening performance for CIN2+ detection, and the cost-effectiveness is not good enough, especially in younger age group.

Objective: To explore the role of HPV viral loads in random biopsy under normal colposcopy. Methods: 908 atypical squamous cells of undetermined significance (ASC-US) and HPV positive women, recruited in cluster sampling in 9 provinces including 5 urban areas and 9 rural areas in China from 1999 to 2008 and meeting the inclusion and exclusion criteria were included in this analysis. According to relative light units/cutoff (RLU/CO) value, subjects were stratified as low (286 cases), intermediate (311 cases) and high (311 cases) viral load groups. Risks of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among different viral load groups were compared with linear trend Chi-square test. Results: Detection rate of CIN3+ in low, intermediate and high viral load groups were 2.1% (6 cases), 2.6% (8 cases) and 6.8% (21 cases) (Chi-square test for trend χ²=8.91, P=0.003) and were 60.3, 74.0 and 201.3 times higher than ASC-US and HPV negative women, respectively. Among 908 subjects, 27.0% (245 cases) were abnormal under colposcopy and 68.6% (623 cases) diagnosed as normal. Under normal colposcopy, detection rate of CIN3+ in low, intermediate and high viral load groups were 0.9% (2 cases), 0.9% (2 cases) and 3.8% (7 cases) (χ²=6.42, P=0.040). Conclusion HPV viral loads display satisfactory risk stratification ability among ASC-US and HPV positive women under normal colposcopy. Women with high HPV viral loads show a significantly increased detection rate of existing CIN3+ and could be recommended to perform random biopsy for histologic diagnosis.

Objective To explore the cooperative mechanism of hospital research management and ethics review.Methods Through the analysis of current ethical conditions,as well as the relationship between hospital research management and ethical review,study on how to integrate them during the management of scientific research project.Results Research management and ethical review have different emphasis from different perspectives,however,both of them serve for research projects which makes inseparable connections.Conclusions Hospital research management and ethical review can be synergistic,according to which the management of scientific research projects will be more reasonable and scientific.