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This Escherichia coli-produced bivalent HPV 16 and 18 vaccine was well tolerated and effective against HPV 16 and 18 associated high-grade genital lesions and persistent infection in interim analysis of this phase 3 trial. We now report data on long-term efficacy and safety after 66 months of follow-up. This phase 3, double-blind, randomised, controlled trial was done in five study sites in China. Eligible participants were women aged 18–45 years, with intact cervix and 1–4 lifetime sexual partners. Women who were pregnant or breastfeeding, had chronic disease or immunodeficiency, or had HPV vaccination history were excluded. Women were stratified by age (18–26 and 27–45 years) and randomly (1:1) allocated by software (block randomisation with 12 codes to a block) to receive three doses of the E coli-produced HPV 16 and 18 vaccine or hepatitis E vaccine (control) and followed-up for 66 months. The primary outcomes were high-grade genital lesions and persistent infection (longer than 6 months) associated with HPV 16 or 18 in the per-protocol susceptible population. This trial was registered with ClinicalTrials.gov, NCT01735006. Between Nov 22, 2012, and April 1, 2013, 8827 women were assessed for eligibility. 1455 women were excluded, and 7372 women were enrolled and randomly assigned to receive the HPV vaccine (n=3689) or control (n=3683). Vaccine efficacy was 100·0% (95% CI 67·2–100·0) against high-grade genital lesions (0 [0%] of 3310 participants in the vaccine group and 13 [0·4%] of 3302 participants in the control group) and 97·3% (89·9–99·7) against persistent infection (2 [0·1%] of 3262 participants in the vaccine group and 73 [2·2%] of 3271 participants in the control group) in the per-protocol population. Serious adverse events occurred at a similar rate between vaccine (267 [7·2%] of 3691 participants) and control groups (290 [7·9%] of 3681); none were considered related to vaccination. The E coli-produced HPV 16 and 18 vaccine was well tolerated and highly efficacious against HPV 16 and 18 associated high-grade genital lesions and persistent infection and would supplement the global HPV vaccine availability and accessibility for cervical cancer prevention. National Natural Science Foundation of China, National Key R&D Program of China, Fujian Provincial Project, Fundamental Funds for the Central Universities, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and Xiamen Innovax.

Objective To observe the effect of acupuncture on the expression of mitochondrial proteome in hippocampus of senescence-accelerated mouse prone 8 (SAMP8) mice models with Alzheimer disease (AD), and to explore the possible protective mechanism of acupuncture on mitochondria. Methods Sixty 6-month-old male SAMP8 mice were randomly divided into an acupuncture at acupoint group, an acupuncture at non-acupoint group and a model group, 20 mice in each group. The 20 male senescence-accelerated mouse/resistance 1 (SAMR1) mice of the same age were used as a normal control group. Shenshu (BL 23), Baihui (GV 20), Xuehai (SP 10) and Geshu (BL 17) were selected for acupuncture intervention in acupuncture at acupoint group. After an 8-week intervention, mitochondrial tissues were extracted from the hippocampus. Differentially expressed proteins were identified by subcellular organelle proteomics. Western blot was used to verify the expressions of some related proteins in hippocampal mitochondria. Results Compared with the model group, there were 13 differentially expressed protein spots in the acupuncture at acupoint group, of which, 9 were up-regulated, including neurofilament light polypeptide (NFL), actin (cytoplasmic 1, database ID: ACTB), tubulin beta-2A chain (TBB2A), tropomodulin-2 (TMOD2), pyruvate dehydrogenase E1 component subunit beta (PDHE1-β), NADH-ubiquinone oxidoreductase 75 kDa subunit (database ID: NDUS1), heat shock cognate 71 kDa protein (HSC71), pyruvate dehydrogenase E1 component subunit alpha (PDHE1-α) and ATP synthase beta subunit (ATP-β); 4 were down-regulated, including glial fibrillary acidic protein (GFAP), pyruvate dehydrogenase phosphatase 1 (PDP1), mitochondrial-processing peptidase subunit alpha (MMP-α) and adenosine kinase (ADK). According to the information provided in the protein database, most of the differentially expressed proteins involve the regulation of mitochondrial function and structure. The expression levels of NFL and TBB2A in the normal control group and the acupuncture at acupoint group were significantly higher than those in the acupuncture at non-acupoint group ( P <0.05). ATP-β and NDUS1 expression levels were significantly higher in the acupuncture at acupoint group than those in the acupuncture at non-acupoint group ( P <0.05); there was no significant difference between the acupuncture at non-acupoint group and the model group ( P >0.05). Conclusion Acupuncture may achieve the potential therapeutic effect on AD by regulating the structure and functional proteins of hippocampal mitochondria.

This study investigates the coupled behavior of the mechanical and electromagnetic responses of a high-temperature superconducting (HTS) no-insulation (NI) racetrack coil. A three-dimensional (3D) equivalent circuit network model and mechanical model with nonlinear contact are incorporated into the coupled model. The stress and separation of adjacent turns under a high magnetic field are analyzed by considering the electromagnetic force and cooling process. The numerical results demonstrate that the straight and curved parts of the racetrack coil exhibit distinct mechanical behaviors. Under a strong external magnetic field, the separation between adjacent turns reduces the charging delay of the coil. The maximum stress occurs in the transition regions between the curved and straight parts. The straight part exhibits a larger rotation angle, while the separation regions between adjacent turns are relatively fewer in those parts. The curved part shows a higher proportion of separation regions in the steady stage. The different separation areas in the straight and curved parts also result in distinct turn-to-turn losses during the charging process. Subsequently, a comparative study is conducted on the influence of residual currents induced by discharging. Finally, the effects of overband and inner diameter on the separation behavior are investigated.

Background： Postoperative preablative stimulated thyroglobulin （ps-Tg） has been evaluated in predicting prognosis and success of ablation regarding differentiated thyroid cancer （DTC）; however, its relationship with recurrence risk and radioiodine decision-making remains uncertain, especially in Chinese DTC patients. We aimed to evaluate the association between ps-Tg and recurrence risk stratification in DTC, to provide incremental values for ps-Tg in postoperative assessment and radioiodine management. Methods： Seven hundred and seven patients with DTC were included; low-risk （L; n = 90）, intermediate-risk （I; n = 283）, and high-risk （H; n = 334, 117 with distant metastasis [M 1 ]） patients were divided according to recurrence risk stratification. The M 1 group was further analyzed regarding evidence of metastasis. Cut-off values of ps-Tg were obtained using receiver operating characteristic analysis. Results： Patients with more advanced disease at initial risk stratification were more likely to have higher ps-Tg levels （I vs. L： P 〈 0.05; H vs. 1： P 〈 0.001; H vs. L： P 〈 0.001）. The corresponding cut-off value of ps-Tg for distinguishing sensitivity and specificity in each of the two groups was 2.95 ng/ml （1 vs. L： 61.5%, 63.3%）, 29.5 ng/ml （H vs, I： 41.9%, 92.6%）, 47.1 ng/ml （M1 vs. M0 in the H group： 79.5%, 88.9%） and 47.1 ng/ml （MI vs. M0 in all patients： 79.5%, 93.7%）. With the cut-offvalue at 47.1 ng/ml, ps-Tg was the only factor that could be used to identify distant metastases, and consequently if measured before radioiodine therapy would prevent 10.26% of patients with M1 from undertreatment, Conclusions： Ps-Tg, as an ongoing reassessment marker, favors differential recurrence risk grading and provides incremental values for radioiodine treatment decision-making.

Background：Wear debris of polyethylene has become a restraining factor of the durability for total hip arthroplasty （THA）.Ceramic on ceramic （COC） has better wear resistance while the squeaking sound and prosthesis fracture are of concern.It is still a controversy that bearing couples are better for THA.Methods：We performed a systematic review of all English articles identified from PubMed （1966-）,Embase （1980-） and the Cochrane Library.Clinical outcomes,complications,revision rates,and radiographic outcomes of COC-THA and ceramic on polyethylene （COP）-THA were compared and evaluated.Results：Eight prospective randomized trials enrolling a total of 1508 patients and 1702 THA surgeries were identified.Our results demonstrated the prosthesis fracture and the squeaking sound is significantly higher in COC group and higher wear rate of the COP.Hip function,loosening rate,dislocation rate,revision rate,and the osteolysis rate were comparable between two groups.According to Grading of Recommendations Assessment,Development and Evaluation system assessment,the strength of evidence was high for prosthesis fracture,dislocation,osteolysis,and moderate for radiolucent line or loosening,hip noise,and revision.Conclusions：Up to now,there is insufficient evidence to identify any clinical advantage of COC compared with COP.Longer follow-up of larger randomized trial is needed to clarify the outcomes.

Yizhijiannao granules have been shown to improve cognitive function in Alzheimer's disease patients. The present study sought to explore the mechanisms involved in the cognitive enhancing effects of Yizhijiannao granule. Senescence-accelerated mouse prone 8 mice with learning and memory disorders were intragastrically treated with Yizhijiannao granule for 8 weeks. Mice intragastrically treated with double distilled water for 8 weeks were considered as the control group. 2D gel electrophoresis was used to isolate total protein from the temporal lobe of senescence-accelerated mouse prone 8 mice, and differential protein spots were obtained by mass spectrometry. Thirty-seven differential protein spots were found in the temporal lobe area of both groups. Ten protein spots were identified: high mobility group box 1, dimethylarginine dimethylaminohydrolase-1, neuroglobin, hemoglobin beta adult major chain, peroxiredoxin-6, cofilin-1, flotillin 1, peptidylprolyl isomerase A, voltage-dependent anion channel-2 and chaperonin containing TCP1, and subunit 2. Among other functions, these proteins are separately involved in the regulation of amyloid beta production, oxidative stress, neuroinflammation, regulation of tau phosphorylation, and regulation of neuronal apoptosis. Our results revealed that Yizhijiannao granule can regulate the expression of various proteins in the temporal lobe of senescence-accelerated mouse prone 8 mice, and may be therapeutically beneficial for the treatment of Alzheimer's disease.

The binding energy,electronic structure and optical properties of H-,H 3 C-,and HS-cluster-passivated ultrathin silicon （single-layer and double-layer） nanosheets were calculated using density functional theory based on the plane-wave ultra-soft pseudopotential.Firstly,the most stable configuration was selected from passivated configurations according to the principle of lowest energy after calculating their total energies.Then the density of state and the band structure of the different passivated systems were calculated.It was found that different passivation clusters could affect the forbidden band,theremore the passivated cluster with sulfur could greatly decrease the width of the forbidden band through electron transfer.Lastly,the light absorption and reflection properties were also investigated.All results were conducive to the development of silicon-based optoelectronic devices.

An increased population of CD4＋CD25highFoxp3＋ regulatory T cells （Tregs） in the tumor-associated microenvi- ronment plays an important role in cancer immune evasion. However, the underlying mechanism remains unclear. Here we observed an increased secretion of miR-214 in various types of human cancers and mouse tumor models. Tumor-secreted miR-214 was sufficiently delivered into recipient T cells by microvesicles （MVs）. In targeted mouse peripheral CD4＋ T cells, tumor-derived miR-214 efficiently downregulated phosphatase and tensin homolog （PTEN） and promoted Treg expansion. The miR-214-induced Tregs secreted higher levels of IL-10 and promoted tumor growth in nude mice. Furthermore, in vivo studies indicated that Treg expansion mediated by cancer cell-secreted miR-214 resulted in enhanced immune suppression and tumor implantation/growth in mice. The MV delivery of anti-miR-214 antisense oligonucleotides （ASOs） into mice implanted with tumors blocked Treg expansion and tumor growth. Our study reveals a novel mechanism through which cancer cell actively manipulates immune response via promoting Treg expansion.

Objective： To explore the mechanism underlying acupuncture regulation of the visual cortex plasticity. Methods： Eighteen kittens of four weeks were randomly divided into 3 groups, a normal group, a model group and an acupuncture group, with six in each group. There was no treatment to those in the normal group. Unilateral eyelid suture method was used to establish the deprivation amblyopia cat model in the model group and the acupuncture group. After that, kittens in the model group didn＇t receive any treatment, but those in the acupuncture group were treated with acupuncture therapy of 12 weeks. Pattern Visual Evoked Potential （P-VEP） and c-Fos protein expression of visual cortex of kittens in each group were tested before and after acupuncture treatment. Results： P-VEP waveform changed significantly in kittens of the model group, the time value of P100was significantly delayed （P〈0.01） and N4s-P100 amplitude was significantly lower （P〈0.01） compared with the normal group. After treatment, the time value of P100in kittens of the acupuncture group was significantly shorter （P〈0.01） and N4s-P100 amplitude was significantly higher （P〈0.01） when compared with the model group. Expression of c-Fos positive neurons can be seen in the visual cortex layers II-IV of kittens in the acupuncture group, and the density and percentage of c-Fos immunoreactive neurons of cortex layers II-IV in kittens of the model group were significantly lower than those in the acupuncture group. Conclusion： Acupuncture has obvious improvement for abnormal changes of P-VEP waveform of monocular visual deprivation kittens; it can also increase the c-Fos protein expression in visual cortex after form- deprived.