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We administered a questionnaire to participants who received different vaccination regimens to evaluate the effectiveness of Ad5-vectored COVID-19 vaccines. The results showed that administration of intramuscular Ad5-nCoV provided 21.32% more protection against SARS-CoV-2 infection than that of the inactivated COVID-19 vaccine in people who had received only one type of COVID-19 vaccine. Furthermore, aerosolized Ad5-nCoV exhibited good protection, whether it was administered as a homologous booster to people vaccinated with the intramuscular Ad5-nCoV or as a heterologous booster to people vaccinated with inactivated COVID-19 vaccines. Our research indicates that Ad5-nCoV is an effective booster. This finding supports the future selection of COVID-19 immunization strategies.

Vaccination strategies that can induce a broad spectrum immune response are important to enhance protection against SARS-CoV-2 variants. We conducted a randomized, double-blind and parallel controlled trial to evaluate the safety and immunogenicity of the bivalent (5×10 10 viral particles) and B.1.1.529 variant (5×10 10 viral particles) adenovirus type-5 (Ad5) vectored COVID-19 vaccines administrated via inhalation. 451 eligible subjects aged 18 years and older who had been vaccinated with three doses inactivated COVID-19 vaccines were randomly assigned to inhale one dose of either B.1.1.529 variant Ad5 vectored COVID-19 vaccine (Ad5-nCoVO-IH group, N=150), bivalent Ad5 vectored COVID-19 vaccine (Ad5-nCoV/O-IH group, N=151), or Ad5 vectored COVID-19 vaccine (5×10 10 viral particles; Ad5-nCoV-IH group, N=150). Adverse reactions reported by 37 (24.67%) participants in the Ad5-nCoVO-IH group, 28 (18.54%) in the Ad5-nCoV/O-IH group, and 26 (17.33%) in the Ad5-nCoV-IH group with mainly mild to moderate dry mouth, oropharyngeal pain, headache, myalgia, cough, fever and fatigue. No serious adverse events related to the vaccine were reported. Investigational vaccines were immunogenic, with significant difference in the GMTs of neutralizing antibodies against Omicron BA.1 between Ad5-nCoV/O-IH (43.70) and Ad5-nCoV-IH (29.25) at 28 days after vaccination (P=0.0238). The seroconversion rates of neutralizing antibodies against BA.1 in Ad5-nCoVO-IH, Ad5-nCoV/O-IH, and Ad5-nCoV-IH groups were 56.00%, 59.60% and 48.67% with no significant difference among the groups. Overall, the investigational vaccines were demonstrated to be safe and well tolerated in adults, and was highly effective in inducing mucosal immunities in addition to humoral and cellular immune responses defending against SARS-CoV-2 variants.Trial registration: Chictr.org identifier: ChiCTR2200063996.

Background: Aerosolised Ad5-nCoV is one of the first licensed mucosal respiratory vaccine against SARS-CoV-2 in the world; however, the safety profile of this vaccine has not been reported in a large population yet., Methods: This multicentre, open-label phase 3 trial, done in 15 centres in six provinces (Jiangsu, Hunan, Anhui, Chongqing, Yunnan, Shandong) in China, aimed to evaluate the safety and immunogenicity of aerosolised Ad5-nCoV in healthy adults (members of the general population with no acute febrile disorders, infectious disease, serious cardiovascular diseases, serious chronic diseases or progressive diseases that cannot be controlled) at least 18 years old, who had received two doses of inactivated COVID-19 vaccine as their primary regimen. This study contained a non-randomly assigned safety cohort and a centrally randomly assigned (1:1) immunogenicity subcohort. The patients in the immunogenicity subcohort received aerosolised Ad5-nCov (aerosolised Ad5-nCoV group) or inactivated vaccine (inactivated COVID-19 group) The primary endpoints were the incidence of adverse reactions within 28 days following the booster vaccination with aerosolised Ad5-nCoV in the safety population (collected through a daily record of any solicited or unsolicited adverse events filled by each participant) and the geometric mean titre of neutralising antibodies at day 28 after the booster dose in the immunogenicity subcohort (measured with a pseudovirus neutralisation test). This study was registered with ClinicalTrials.gov, NCT05204589., Findings: Between Jan 22, 2022, and March 12, 2022, we recruited 11 410 participants who were screened for eligibility, of whom 10 267 (99·8%) participants (5738 [55·9%] men, 4529 [44·1%] women; median age 53 years [18-92]) received the study drugs: 9847 (95·9%) participants in the open-label cohort to receive aerosolised Ad5-nCoV, and 420 (4·1%) in the immunogenicity subcohort (212 in the aerosolised Ad5-nCoV group and 208 in the inactivated vaccine group). Adverse reactions were reported by 1299 (13%) of 10 059 participants within 28 days after receiving the booster vaccination with aerosolised Ad5-nCoV, but most of the adverse reactions reported were mild to moderate in severity. Participants in the aerosolised Ad5-nCoV group had a significantly higher level of the neutralising antibodies against omicron BA.4/5 (GMT 107·7 [95% CI 88·8-130·7]) than did those in the inactivated vaccine group (17·2 [16·3-18·2]) at day 28., Interpretation: The heterologous booster regimen with aerosolised Ad5-nCoV is safe and highly immunogenic, boosting both systemic and mucosal immunity against omicron subvariants., Funding: National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests J-BG and TZ are employees of CanSino Biologics. All the other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Heterologous booster immunisation with orally administered aerosolised Ad5-nCoV vaccine (AAd5) has been shown to be safe and highly immunogenic in adults. Here, we aimed to assess the safety and immunogenicity of heterologous booster immunisation with orally administered AAd5 in children and adolescents aged 6-17 years who had received two doses of inactivated vaccine (BBIBP-CorV or CoronaVac)., Methods: We did a randomised, open-label, parallel-controlled, non-inferiority study to assess the safety and immunogenicity of heterologous booster immunisation with AAd5 (0·1 mL) or intramuscular Ad5-nCoV vaccine (IMAd5; 0·3 mL) and homologous booster immunisation with inactivated vaccine (BBIBP-CorV or CoronaVac; 0·5 mL) in children (aged 6-12 years) and adolescents (aged 13-17 years) who had received two doses of inactivated vaccine at least 3 months earlier in Hunan, China. Children and adolescents who were previously immunised with two-dose BBIBP-CorV or CoronaVac were recruited for eligibility screening at least 3 months after the second dose. A stratified block method was used for randomisation, and participants were stratified by age and randomly assigned (3:1:1) to receive AAd5, IMAd5, or inactivated vaccine. The study staff and participants were not masked to treatment allocation. Laboratory and statistical staff were masked during the study. In this interim analysis, adverse events within 14 days and geometric mean titre (GMT) of serum neutralising antibodies on day 28 after the booster vaccination, based on the per-protocol population, were used as the primary outcomes. The analysis of non-inferiority was based on comparison using a one-sided 97·5% CI with a non-inferiority margin of 0·67. This study was registered at ClinicalTrials.gov, NCT05330871, and is ongoing., Findings: Between April 17 and May 28, 2022, 436 participants were screened and 360 were enrolled: 220 received AAd5, 70 received IMAd5, and 70 received inactivated vaccine. Within 14 days after booster vaccination, vaccine-related adverse reactions were reported: 35 adverse events (in 13 [12%] of 110 children and 22 [20%] of 110 adolescents) in 220 individuals in the AAd5 group, 35 (in 18 [51%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 13 (in five [14%] of 35 children and eight [23%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. Solicited adverse reactions were also reported: 34 (13 [12%] of 110 children and 21 [10%] of 110 adolescents) in 220 individuals in the AAd5 group, 34 (17 [49%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 12 (five [14%] of 35 children and seven [20%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. The GMTs of neutralising antibodies against ancestral SARS-CoV-2 Wuhan-Hu-1 (Pango lineage B) in the AAd5 group were significantly higher than the GMTs in the inactivated vaccine group (adjusted GMT ratio 10·2 [95% CI 8·0-13·1]; p<0·0001)., Interpretation: Our study shows that a heterologous booster with AAd5 is safe and highly immunogenic against ancestral SARS-CoV-2 Wuhan-Hu-1 in children and adolescents., Funding: National Key R&D Program of China., Competing Interests: Declaration of interests J-BG, H-TH, XW, and HL are employees of CanSino Biologics. The other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Aerosolised Ad5-nCoV is the first approved mucosal respiratory COVID-19 vaccine to be used as a booster after the primary immunisation with COVID-19 vaccines. This study aimed to evaluate the safety and immunogenicity of aerosolised Ad5-nCoV, intramuscular Ad5-nCoV, or inactivated COVID-19 vaccine CoronaVac given as the second booster., Methods: This is an open-label, parallel-controlled, phase 4 randomised trial enrolling healthy adult participants (≥18 years) who had completed a two-dose primary immunisation and a booster immunisation with inactivated COVID-19 vaccines (CoronaVac only) at least 6 months before, in Lianshui and Donghai counties, Jiangsu Province, China. We recruited eligible participants from previous trials in China (NCT04892459, NCT04952727, and NCT05043259) as cohort 1 (with the serum before and after the first booster dose available), and from eligible volunteers in Lianshui and Donghai counties, Jiangsu Province, as cohort 2. Participants were randomly assigned at a ratio of 1:1:1, using a web-based interactive response randomisation system, to receive the fourth dose (second booster) of aerosolised Ad5-nCoV (0·1 mL of 1·0 × 10 11 viral particles per mL), intramuscular Ad5-nCoV (0·5 mL of 1·0 × 10 11 viral particles per mL), or inactivated COVID-19 vaccine CoronaVac (0·5 mL), respectively. The co-primary outcomes were safety and immunogenicity of geometric mean titres (GMTs) of serum neutralising antibodies against prototype live SARS-CoV-2 virus 28 days after the vaccination, assessed on a per-protocol basis. Non-inferiority or superiority was achieved when the lower limit of the 95% CI of the GMT ratio (heterologous group vs homologous group) exceeded 0·67 or 1·0, respectively. This study was registered with ClinicalTrials.gov, NCT05303584 and is ongoing., Findings: Between April 23 and May 23, 2022, from 367 volunteers screened for eligibility, 356 participants met eligibility criteria and received a dose of aerosolised Ad5-nCoV (n=117), intramuscular Ad5-nCoV (n=120), or CoronaVac (n=119). Within 28 days of booster vaccination, participants in the intramuscular Ad5-nCoV group reported a significantly higher frequency of adverse reactions than those in the aerosolised Ad5-nCoV and intramuscular CoronaVac groups (30% vs 9% and 14%, respectively; p<0·0001). No serious adverse events related to the vaccination were reported. The heterologous boosting with aerosolised Ad5-nCoV triggered a GMT of 672·4 (95% CI 539·7-837·7) and intramuscular Ad5-nCoV triggered a serum neutralising antibody GMT of 582·6 (505·0-672·2) 28 days after the booster dose, both of which were significantly higher than the GMT in the CoronaVac group (58·5 [48·0-71·4]; p<0·0001)., Interpretation: A heterologous fourth dose (second booster) with either aerosolised Ad5-nCoV or intramuscular Ad5-nCoV was safe and highly immunogenic in healthy adults who had been immunised with three doses of CoronaVac., Funding: National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan., Competing Interests: Declaration of interests J-BG is an employee of CanSino Biologics. Tao Zhu owns stock in CanSino Biologics. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: People over 60 have been found to develop less protection after two doses of inactivated COVID-19 vaccines than younger people. Heterologous immunisation could potentially induce more robust immune responses compared to homologous immunisation. We aimed to assess the immunogenicity and safety of a heterologous immunisation with an adenovirus type 5-vectored vaccine (Ad5-nCOV, Convidecia) among elderly who were primed with an inactivated vaccine (CoronaVac) previously., Methods: We did a randomised, observer-blinded, non-inferiority trial in healthy adults aged 60 years and older in Lianshui County (Jiangsu, China) between August 26, 2021 and May 15, 2022. 199 eligible participants who had received two doses of CoronaVac in the past 3-6 months were randomised (1:1) to receive a third dose of Convidecia (group A, n = 99) or CoronaVac (group B, n = 100), while 100 participants primed with one dose of CoronaVac in the past 1-2 months were randomised equally to receive a second dose of Convidecia (group C, n = 50) or CoronaVac (group D, n = 50). Participants and investigators were masked to the vaccine received. Primary outcomes were the geometric mean titers (GMTs) of neutralising antibodies against live SARS-CoV-2 virus 14 days after boosting and 28-day adverse reactions. This study was registered with ClinicalTrials.govNCT04952727., Findings: A heterologous third dose of Convidecia resulted in a 6.2-fold (GMTs: 286.4 vs 48.2), 6.3-fold (45.9 vs 7.3) and 7.5-fold (32.9 vs 4.4) increase in neutralising antibodies against SARS-CoV-2 wild-type, delta (B.1.617.2) and omicron (BA.1.1) 14 days post boosting, respectively, compared with the homologous boost. The heterologous booster with Convidecia induced significantly higher neutralsing activities, with up to 91% inhibition in binding of Spike to ACE2 for BA.4 and BA.5 variants, compared with 35% inhibition induced by three doses of CoronaVac. For participants primed with one dose of CoronaVac, a heterologous dose of Convidecia induced higher neutralising antibodies against wild-type than two doses of CoronaVac (GMTs: 70.9 vs 9.3, p < 0.0001), but not for that against variants of concern (GMTs against delta: 5.0 vs 4.0, p = 0.4876; GMTs against omicron: 4.8 vs 3.7, p = 0.4707). Adverse reactions were reported by 8 (8.1%) participants in group A and 4 (4.0%) in group B (p ＞ 0.05), and 8 (16.0%) in group C and 1 (2.0%) in group D (p = 0.031)., Interpretation: In elderly individuals primed with two doses of CoronaVac, the heterologous immunisation with Convidecia induced strong antibodies against SARS-CoV-2 wildtype and variants of concern, which could be an alternative regimen for enhancing protection in this vulnerable population., Funding: National Natural Science Foundation of China, Jiangsu Provincial Key Research and Development Program, and Jiangsu Science Fund for Distinguished Young Scholars Program., Competing Interests: J.G., T.Z., H.H., X.W., and P.W. are employees of CanSino Biologics. All the other authors declare no competing interests., (© 2023 Published by Elsevier Ltd.)

Background: The demonstration of batch-to-batch consistency is indispensable for quality control of vaccines., Methods: We conducted a randomized, double-blind, parallel-controlled trial to evaluate the immunogenicity consistency of a single shot of Ad5-nCoV in healthy adults who had not previously received any COVID-19 vaccine. All eligible participants were randomly assigned equally to receive one of the three consecutive batches of Ad5-nCoV (5 × 10 10 viral particles/vial, 0.5 mL). The primary endpoint was geometric mean titers (GMTs) of serum SARS-CoV-2 receptor-binding domain (RBD)-specific IgG on day 28 post-vaccination., Results: One thousand fifty participants were enrolled, with 350 (33%) participants per group. On day 28 post-vaccination, GMTs in three groups were 78.3 binding antibody units (BAU)/mL (95% CI 70.3-87.3), 82.9 BAU/mL (73.9-92.9), and 78.8 BAU/mL (70.2-88.4), respectively. The two-sided 95% CIs for the GMT ratios between each pair of batches were all between 0.67 and 1.5. The highest incidence of solicited adverse reactions within 7 days post-vaccination was reported by batch 3 recipients (23.1% versus 15.1% in batch 1 recipients and 14.6% in bath 2 recipients; p = 0.0039). None of the serious adverse events were related to vaccination., Conclusions: Immunogenicity consistency between consecutive batches of Ad5-nCoV was well established in adults., Clinical Trial Registration: This trial was registered with ClinicalTrials.gov (NCT05313646).

Background: Due to waning immunity and protection against infection with SARS-CoV-2, a third dose of a homologous or heterologous COVID-19 vaccine has been proposed by health agencies for individuals who were previously primed with two doses of an inactivated COVID-19 vaccine., Methods: We did a randomised, open-label, controlled trial to evaluate the safety and immunogenicity of heterologous boost immunisation with an orally administered aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in Chinese adults (≥18 years old) who had previously received two doses of an inactivated SARS-CoV-2 vaccine-Sinovac CoronaVac. Eligible participants were randomly assigned (1:1:1) to receive a heterologous booster vaccination with a low dose (1·0 × 10 11 viral particles per mL; 0·1 mL; low dose group), or a high dose (1·0 × 10 11 viral particles per mL; 0·2 mL; high dose group) aerosolised Ad5-nCoV, or a homologous intramuscular vaccination with CoronaVac (0·5 mL). Only laboratory staff were masked to group assignment. The primary endpoint for safety was the incidence of adverse reactions within 14 days after the booster dose. The primary endpoint for immunogenicity was the geometric mean titres (GMTs) of serum neutralising antibodies (NAbs) against live SARS-CoV-2 virus 14 days after the booster dose. This study was registered with ClinicalTrials.gov, NCT05043259., Findings: Between Sept 14 and 16, 2021, 420 participants were enrolled: 140 (33%) participants per group. Adverse reactions were reported by 26 (19%) participants in the low dose group and 33 (24%) in the high dose group within 14 days after the booster vaccination, significantly less than the 54 (39%) participants in the CoronaVac group (p<0·0001). The low dose group had a serum NAb GMT of 744·4 (95% CI 520·1-1065·6) and the high dose group had a GMT of 714·1 (479·4-1063·7) 14 days after booster dose, significantly higher than the GMT in the CoronaVac group (78·5 [60·5-101·7]; p<0·0001)., Interpretation: We found that a heterologous booster vaccine with an orally administered aerosolised Ad5-nCoV is safe and highly immunogenic in adults who have previously received two doses of CoronaVac as the primary series vaccination., Funding: National Natural Science Foundation of China and Jiangsu Provincial Key Research and Development Program., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: The 12-item Chinese Health Questionnaire (CHQ-12) has been widely used for screening mental disorders. This study aims to examine the internal consistency and factor structure of CHQ-12 and its suitability for use in the elderly Chinese population., Study Design: This is a cross-sectional study., Methods: A total of 8526 elderly people aged ≥60 years from 11 cities in Shanxi Province were selected for participation in this study by stratified random cluster sampling. Cronbach's alpha was employed to assess internal consistency. An exploratory factor analysis (EFA) was performed to explore the underlying factor structure of the CHQ-12 in the elderly. A confirmatory factor analysis (CFA) was then conducted to test and compare the goodness-of-fit between possible factor structure obtained from the EFA and the unidimensional structure, which was originally recommended., Results: The Cronbach's alpha for CHQ-12 was 0.838. The EFA extracted three factors, which explained 55.985% of the total variance of the data. The CFA of the three-factor model resulted in an acceptable model fit (Comparative Fit Index = 0.98, Tucker-Lewis Index = 0.97, Normed Fit Index = 0.98, Expected Cross-Validation Index = 0.28, Root-Mean-Square Error of Approximation = 0.071). The item loadings ranged from 0.58 to 0.82. Correlation coefficients among the three factors ranged from 0.40 to 0.75., Conclusions: The CHQ-12 presented satisfactory internal consistency and structural validity in the Chinese elderly population. The CFA of the three-factor structure expressed a preferred model fit in comparison to the unidimensional model. The three-factor structure of the CHQ-12 interpreted three different aspects of mental health: somatic symptoms, anxiety and worry, and depression/poor family relationship., (Copyright © 2020 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an appropriate dose of the candidate vaccine for an efficacy study., Methods: This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 10 11 viral particles per mL or 5 × 10 10 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389., Findings: 603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 10 11 viral particles n=253; 5 × 10 10 viral particles n=129) or placebo (n=126). In the 1 × 10 11 and 5 × 10 10 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2-749·2) and 571·0 (467·6-697·3), with seroconversion rates at 96% (95% CI 93-98) and 97% (92-99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8-22·7) and 18·3 (14·4-23·3) in participants receiving 1 × 10 11 and 5 × 10 10 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85-93) of 253 and 113 (88%, 81-92) of 129 participants in the 1 × 10 11 and 5 × 10 10 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 10 11 and 5 × 10 10 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 10 11 viral particles dose group and one (1%) participant in the 5 × 10 10 viral particles dose group. No serious adverse reactions were documented., Interpretation: The Ad5-vectored COVID-19 vaccine at 5 × 10 10 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation., Funding: National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aim: To investigate the correlation of ischemic ophthalmopathy (IO) with lacunar infarction (LI), an ischemic lesions in the cerebrovascular system., Methods: Totally 204 cases of IO without any nervous system symptom and previously diagnosed LI served as the observational group. All 204 cases without IO, nervous system symptoms and previous LI served as the control group. Age and sex between the two groups matched well. LI was diagnosed by magnetic resonance imaging (MRI) and the results of the two groups were statistically analyzed and compared., Results: IO included 174 eyes of 156 patients with non-arteritis anterior ischemic optic neuropathy (NAION), 42 eyes of 36 patients with central retinal artery occlusion (CRAO) or branch retinal artery occlusion (BRAO) and 12 eyes of 12 patients with ocular ischemia syndrome (OIS).The detection rate of LI (72.54%) in IO group was obviously higher than that (15.68%) in the control group ( P <0.001). IO was positively correlated with LI ( r =0.573, P <0.05). In addition, most infarction sites located in the basal ganglia (67.57%), which were not the vital areas of cerebrum and not easy to be found due to their small size. The majority of those first visited IO patients (72.54%) without nervous system symptom and previously diagnosed LI had already suffered from LI., Conclusion: According to our studies, there is a positive correlation between IO and LI. IO can be used as an important predictor for the present of LI, especially obvious signs of the patient., (International Journal of Ophthalmology Press.)

Background: A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain., Methods: We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 10 10 , 1 × 10 11 , and 1·5 × 10 11 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127., Findings: Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination., Interpretation: The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation., Funding: National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Kangfu Xiaoyan Suppository is widely used in the treatment of gynecological inflammatory diseases. Long-term clinical application and a certain amount of research evidences show that Kangfu Xiaoyan Suppository can alleviate the clinical symptoms of pelvic inflammatory diseases,reduce the recurrence rate,and relieve sequelae,with a better safety and economic characteristics. As a type of nationally protected traditional Chinese medicine and type B medicine included in medical insurance,it has been selected as a Chinese patent medicine for rectal administration. It was included in the Guidelines for diagnosis and treatment of common gynecological diseases of traditional Chinese medicine published by the Chinese Academy of Traditional Chinese Medicine in 2012,the Pelvic inflammatory diseases diagnosis and treatment guidelines issued by the Infectious Diseases Collaborative Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association in 2014,and the group standard of Single use of traditional Chinese medicine/combined antibiot guidelines for clinical practice-pelvic inflammatory diseases of the Chinese Academy of Traditional Chinese Medicine in 2017. To further enhance clinicians' understanding of the drug and better guide its rational clinical use,experts from the field of gynecology of traditional Chinese and Western medicine were invited to develop and compile this expert consensus. This consensus takes full account of clinical evidences and expert clinical experience,and form recommendations for clinical problems based on evidences and consensus recommendations for clinical problems without evidence by nominal grouping method. The expert consensus is mainly formed in the consideration of six factors: quality of evidence,economy,efficacy,adverse reactions,patient acceptability and others. Based on clinical research evidences and expert experience,this consensus provides a preliminary reference for the clinical use of the drug in a concise and clear format. However,evidence-based support is still required in a large number of high-quality studies,and this consensus will be revised in the future according to new clinical problems and the update of evidence-based evidence in practical application.

Importance: Acupuncture is used to induce ovulation in some women with polycystic ovary syndrome, without supporting clinical evidence., Objective: To assess whether active acupuncture, either alone or combined with clomiphene, increases the likelihood of live births among women with polycystic ovary syndrome., Design, Setting, and Participants: A double-blind (clomiphene vs placebo), single-blind (active vs control acupuncture) factorial trial was conducted at 21 sites (27 hospitals) in mainland China between July 6, 2012, and November 18, 2014, with 10 months of pregnancy follow-up until October 7, 2015. Chinese women with polycystic ovary syndrome were randomized in a 1:1:1:1 ratio to 4 groups., Interventions: Active or control acupuncture administered twice a week for 30 minutes per treatment and clomiphene or placebo administered for 5 days per cycle, for up to 4 cycles. The active acupuncture group received deep needle insertion with combined manual and low-frequency electrical stimulation; the control acupuncture group received superficial needle insertion, no manual stimulation, and mock electricity., Main Outcomes and Measures: The primary outcome was live birth. Secondary outcomes included adverse events., Results: Among the 1000 randomized women (mean [SD] age, 27.9 [3.3] years; mean [SD] body mass index, 24.2 [4.3]), 250 were randomized to each group; a total of 926 women (92.6%) completed the trial. Live births occurred in 69 of 235 women (29.4%) in the active acupuncture plus clomiphene group, 66 of 236 (28.0%) in the control acupuncture plus clomiphene group, 31 of 223 (13.9%) in the active acupuncture plus placebo group, and 39 of 232 (16.8%) in the control acupuncture plus placebo group. There was no significant interaction between active acupuncture and clomiphene (P = .39), so main effects were evaluated. The live birth rate was significantly higher in the women treated with clomiphene than with placebo (135 of 471 [28.7%] vs 70 of 455 [15.4%], respectively; difference, 13.3%; 95% CI, 8.0% to 18.5%) and not significantly different between women treated with active vs control acupuncture (100 of 458 [21.8%] vs 105 of 468 [22.4%], respectively; difference, -0.6%; 95% CI, -5.9% to 4.7%). Diarrhea and bruising were more common in patients receiving active acupuncture than control acupuncture (diarrhea: 25 of 500 [5.0%] vs 8 of 500 [1.6%], respectively; difference, 3.4%; 95% CI, 1.2% to 5.6%; bruising: 37 of 500 [7.4%] vs 9 of 500 [1.8%], respectively; difference, 5.6%; 95% CI, 3.0% to 8.2%)., Conclusions and Relevance: Among Chinese women with polycystic ovary syndrome, the use of acupuncture with or without clomiphene, compared with control acupuncture and placebo, did not increase live births. This finding does not support acupuncture as an infertility treatment in such women., Trial Registration: clinicaltrials.gov Identifier: NCT01573858.

Background: The 2013-15 Ebola virus disease epidemic in west Africa greatly accelerated the development of Ebola vaccine. We aimed to analyse the immune persistence induced by one shot of an adenovirus type-5 vector-based Ebola virus vaccine up to 6 months and the effect of boosting with a homologous vector in healthy adults in China., Methods: In a randomised, double-blind, placebo-controlled, phase 1 clinical trial in one site in Jiangsu Province, China, 120 healthy adults aged 18-60 years received an initial dose of intramuscular adenovirus type-5 Ebola virus vaccine of 4·0 × 10 10 viral particles, 1·6 × 10 11 viral particles, or placebo, and were followed up to day 168. Participants were subsequently re-recruited to receive a booster dose of the same vaccine or placebo, in the same dose, at month 6. Women who were pregnant, breastfeeding, or planned to become pregnant during the next month were excluded. Randomisation was conducted by computer-generated block randomisation. Randomisation data were unmasked for interim analysis of the data obtained between days 0-28 but not disclosed to participants or site staff. Safety and immunogenicity analysis were done on the intention-to-treat population. We aimed to assess the safety profile of the experimental vaccine and the immunity responses to a single-dose immunisation or a homologous prime-boost regimen. Primary outcomes were Ebola glycoprotein-specific ELISA antibody responses 28 days post-boost and the occurrences of adverse reactions post-boost. The original trial and the extended booster study were registered with ClinicalTrials.gov, numbers NCT02326194 and NCT02533791, respectively., Findings: Between Dec 28, 2014, and Jan 9, 2015, we enrolled 210 volunteers. 90 participants were not randomised due to not meeting inclusion criteria (61), meeting exclusion criteria (4), or withdrawal of consent (25). 120 people were randomly assigned to receive intramuscular Ebola vaccine at 4·0 × 10 10 viral particles (low dose, n=40), Ebola vaccine at 1·6 × 10 11 viral particles (high dose, n=40), or placebo (n=40, in two groups of 20). After prime vaccination, the geometric mean titer (GMT) of ELISA EC 90 peaked at 682·7 (95% CI 424·3-1098·5) in the low-dose vaccine group and 1305·7 (970·1-1757·2) in the high-dose vaccine group at day 28, and then fell gradually through the next a few months to 575·5 (394·8-838·8) in the high-dose vaccine group and 197·9 (107·9-362·7) in the low-dose vaccine group at day 168. No specific response was recorded in the placebo group with a GMT of 5·0. Of the 120 participants involved in the initial trial, ten participants declined to participate, and 110 were included in the boost immunisation: 38 received the low dose, 35 received the high dose, and 37 received the placebo. At day 28 after boost vaccination, the ELISA EC 90 titres rapidly rose to 6110 (95% CI 4705-7935) in the low-dose group and to 11825 (8904-15705) in the high dose group. 78 of 110 participants reported at least one solicited adverse reaction within the first 7 days after booster administration. Both of the groups who received vaccine showed significantly higher incidence of mild or moderate solicited adverse reactions than did the placebo group., Interpretation: The adenovirus 5-vectored Ebola vaccine of 1·6 × 10 11 viral particles was highly immunogenic and safe. The lower dose of 4·0 × 10 10 viral particles was also safe, but immunogenicity seemed to be more vulnerable to the pre-existing immunity of adenovirus 5. A homologous priming-boosting regimen with adenovirus type-5 Ebola vaccine at 6 months interval was able to elicit greater antibody responses with longer duration. These results support an immunisation strategy to implement a booster injection for a more durable protection against Ebola virus disease., Funding: Chinese Ministry of Science and Technology and The National Health and Family Planning Commission, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license. Published by Elsevier Ltd.. All rights reserved.)

Background: A recombinant adenovirus type-5 vector-based vaccine expressing the glycoprotein of Ebola Zaire Makona variant showed good safety and immunogenicity in a phase 1 trial of healthy Chinese adults. We aimed to assess the safety and immunogenicity of this vaccine in healthy adults in Sierra Leone and to determine the optimal dose., Methods: We did a single-centre, randomised, double-blind, placebo-controlled, phase 2 clinical trial at Sierra Leone-China Friendship Hospital, Freetown, Sierra Leone. We recruited healthy adults aged 18-50 years who were HIV negative, had no history of Ebola virus infection, and had no previous immunisation with other Ebola vaccine candidates. Participants were sequentially enrolled and randomly assigned (2:1:1), by computer-generated block randomisation (block size of eight), to receive the high-dose vaccine (1·6 × 10 11 viral particles), low-dose vaccine (8·0 × 10 10 viral particles), or placebo (containing only vaccine excipients, with no viral particles). Participants, investigators, and study staff (except two study pharmacists) were masked from treatment allocation. The primary safety outcome was occurrence of solicited adverse reactions within 7 days of vaccination, analysed by intention to treat. The primary immunogenicity outcome was glycoprotein-specific antibody responses at days 14, 28, and 168 after vaccination, analysed in all vaccinated participants who had blood samples drawn for antibody tests. The trial is registered with the Pan African Clinical Trials Registry, number PACTR201509001259869, and is completed., Findings: During Oct 10-28, 2015, 500 participants were enrolled and randomly assigned to receive the high-dose vaccine (n=250), low-dose vaccine (n=125), or placebo (n=125). 132 (53%) participants in the high-dose group, 60 (48%) in the low-dose group, and 54 (43%) in the placebo group reported at least one solicited adverse reaction within 7 days of vaccination. Most adverse reactions were mild and self-limiting. Solicited injection-site adverse reactions were significantly more frequent in vaccine recipients (65 [26%] in high-dose group and 31 [25%] in low-dose group) than in those receiving placebo (17 [14%]; p=0·0169). Glycoprotein-specific antibody responses were detected from day 14 onwards (geometric mean titre 1251·0 [95% CI 976·6-1602·5] in low-dose group and 1728·4 [1459·4-2047·0] in high-dose group) and peaked at day 28 (1471·8 [1151·0-1881·8] and 2043·1 [1762·4-2368·4]), but declined quickly in the following months (223·3 [148·2-336·4] and 254·2 [185·0-349·5] at day 168). Geometric mean titres in the placebo group remained around 6·0-6·8 throughout the study period. Three serious adverse events (malaria, gastroenteritis, and one fatal asthma episode) were reported in the high-dose vaccine group, but none was deemed related to the vaccine., Interpretation: The recombinant adenovirus type-5 vector-based Ebola vaccine was safe and highly immunogenic in healthy Sierra Leonean adults, and 8·0 × 10 10 viral particles was the optimal dose., Funding: Chinese Ministry of Science and Technology and the National Health and Family Planning Commission, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The fermentation performance of a genome-shuffled strain of Candida versatilis S3-5, isolated for improved tolerance to salt, and wild-type (WT) strain were analysed. The fermentation parameters, such as growth, reducing sugar, ethanol, organic acids and volatile compounds, were detected during soy sauce fermentation process., Results: The results showed that ethanol produced by the genome shuffled strain S3-5 was increasing at a faster rate and to a greater extent than WT. At the end of the fermentation, malic acid, citric acid and succinic acid formed in tricarboxylic acid cycle after S3-5 treatment elevated by 39.20%, 6.85% and 17.09% compared to WT, respectively. Moreover, flavour compounds such as phenethyl acetate, ethyl vanillate, ethyl acetate, isoamyl acetate, ethyl myristate, ethyl pentadecanoate, ethyl palmitate and phenylacetaldehyde produced by S3-5 were 2.26, 2.12, 2.87, 34.41, 6.32, 13.64, 2.23 and 78.85 times as compared to WT., Conclusions: S3-5 exhibited enhanced metabolic ability as compared to the wild-type strain, improved conversion of sugars to ethanol, metabolism of organic acid and formation of volatile compounds, especially esters, Moreover, S3-5 might be an ester-flavour type salt-tolerant yeast. © 2016 Society of Chemical Industry., (© 2016 Society of Chemical Industry.)

Objective: To reduce the fermentation cost in very high gravity fermentations of ethanol using Saccharomyces cerevisiae, whole cell directed evolution approaches were carried out., Results: The methods used included cell ploidy manipulation, global transcription machinery engineering and genome shuffling. Ethanol production by the four methods was improved compared with the control. Notably, the ethanol yield of a strain constructed by genome shuffling was enhanced by up to 11 % more than the control reaching 120 g ethanol/l in 35 h using a very high gravity fermentation with 300 g glucose/l., Conclusion: Genome shuffling can create strains with improved fermentation characteristics in very high gravity fermentations.

Background: Up to now, all tested Ebola virus vaccines have been based on the virus strain from the Zaire outbreak in 1976. We aimed to assess the safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine expressing the glycoprotein of the 2014 epidemic strain., Methods: We did this randomised, double-blind, placebo-controlled, phase 1 clinical trial at one site in Taizhou County, Jiangsu Province, China. Healthy adults (aged 18-60 years) were sequentially enrolled and randomly assigned (2:1), by computer-generated block randomisation (block size of six), to receive placebo, low-dose adenovirus type-5 vector-based Ebola vaccine, or high-dose vaccine. Randomisation was pre-stratified by dose group. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was occurrence of solicited adverse reactions within 7 days of vaccination. The primary immunogenicity endpoints were glycoprotein-specific antibody titres and T-cell responses at day 28 after the vaccination. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT02326194., Findings: Between Dec 28, 2014, and Jan 9, 2015, 120 participants were enrolled and randomly assigned to receive placebo (n=40), low-dose vaccine (n=40), or high-dose vaccine. Participants were followed up for 28 days. Overall, 82 (68%) participants reported at least one solicited adverse reaction within 7 days of vaccination (n=19 in the placebo group vs n=27 in the low-dose group vs n=36 in the high-dose group; p=0·0002). The most common reaction was mild pain at the injection site, which was reported in eight (20%) participants in the placebo group, 14 (35%) participants in the low-dose group, and 29 (73%) participants in the high-dose vaccine group (p<0·0001). We recorded no statistical differences in other adverse reactions and laboratory tests across groups. Glycoprotein-specific antibody titres were significantly increased in participants in the low-dose and high-dose vaccine groups at both day 14 (geometric mean titre 421·4 [95% CI 249·7-711·3] and 820·5 [598·9-1124·0], respectively; p<0·0001) and day 28 (682·7 [424·3-1098·5] and 1305·7 [970·1-1757·2], respectively; p<0·0001). T-cell responses peaked at day 14 at a median of 465·0 spot-forming cells (IQR 180·0-1202·5) in participants in the low-dose group and 765·0 cells (400·0-1460·0) in those in the high-dose group. 21 (18%) participants had mild fever (n=9 in the placebo group, n=6 in the low-dose group, and n=6 in the high-dose group). No serious adverse events were recorded., Interpretation: Our findings show that the high-dose vaccine is safe and robustly immunogenic. One shot of the high-dose vaccine could mount glycoprotein-specific humoral and T-cell response against Ebola virus in 14 days., Funding: China National Science and Technology, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

As one of the major microbes in the soy sauce fermentation, Candida versatilis enriches the flavor and improves the quality of soy sauce. In this study, a combination of five different GC-MS and LC-MS-based metabolome analytical approaches was used to analyze the intracellular, extracellular and whole metabolites of C. versatilis. Our results found out that a total of 132, 244 and 267 different metabolites were detectable from the intracellular, extracellular and whole part, respectively. When exposed to 0. 9 and 18 % salt, respectively, 114, 123 and 129 different intracellular metabolites, 184, 200 and 178 extracellular metabolites and 177, 188 and 186 whole metabolites were detected, respectively. Our data showed that salt enhances the metabolic capacity of C. versatilis, especially its amino acid and enhances the synthesis and secretion of some metabolites of C. versatilis, especially the aldehydes and phenols, such as vanillin, guaiacol and 5-hydroxymethylfurfural. Our data also showed that special attention has to be paid to the generation of biogenic amines when C. versatilis was treated with salt.

Objective: Obesity is a common feature in women with polycystic ovary syndrome (PCOS) and potentially significantly influences reproductive function. However, opinions are divided as to which factor is a more appropriate obesity predictor of reproductive outcomes. The aim of this study was to investigate the discriminatory capability of anthropometric measures in predicting reproductive outcomes in Chinese women with PCOS. Methods: A total of 998 women with PCOS from PCOSAct were included. Logistic regression models were used to compute the odds ratios (ORs) and 95% confidence interval (95% CIs) to assess the effect of anthropometric measures, including body mass index (BMI), waist circumference (WC), hip circumference (HC), the waist‒hip ratio (WHR) and the waist‒height ratio (WHtR), on reproductive outcomes. The discrimination abilities of the models were assessed and compared based on the area under the receiver operating characteristic curve (AUC), Akaike's information criterion (AIC) and integrated discrimination improvement (IDI). Results: Among PCOS women, there was a graded association between anthropometric measures and predicted reproductive outcomes across quintiles of anthropometric measures, including a linear association among WHR, BMI and reproductive outcomes and among waist circumference, WHtR and live birth, pregnancy, and ovulation. However, only a linear association was noted between the hip and ovulation. C-statistic comparisons and IDI analyses revealed a trend towards a significant superiority of BMI for ovulation and WHR for live birth, pregnancy and conception in the models. Combining obesity variables improved discrimination in the multivariable models for reproductive outcomes. Conclusions: Our findings support that BMI is a better predictor of ovulation and that the WHR is a better predictor of live birth, pregnancy and conception, whereas the combination of obesity variables contributes to the discrimination of reproduction. [ABSTRACT FROM AUTHOR]

Background: Natural infection or vaccination have provided robust immune defense against SARS-CoV-2 invasion, nevertheless, Omicron variants still successfully cause breakthrough infection, and the underlying mechanisms are poorly understood. Methods: Sequential blood samples were continuously collected at different time points from 252 volunteers who were received the CanSino Ad5-nCoV (n = 183) vaccine or the Sinovac CoronaVac inactivated vaccine (n= 69). The anti- SARS-CoV-2 prototype and Omicron BA.5.2 as well as XBB.1.16 variant neutralizing antibodies (Nab) in sera were detected by ELISA. Sera were also used to measure pseudo and live virus neutralization assay. The associations between the anti-prototype Nab levels and different HLA-ABC alleles were analyzed using artificial intelligence (AI)-deep learning techniques. The frequency of B cells in PBMCs was investigated by flow cytometry assay (FACs). Results: Individuals carrying the HLA-B*15 allele manifested the highest concentrations of anti-SARS-CoV-2 prototype Nab after vax administration. Unfortunately, these volunteers are more susceptible to Omicron BA.5.2 breakthrough infection due to their sera have poorer anti-BA.5.2 Nab and lower levels of viral neutralization efficacy. FACs confirmed that a significant decrease in CD19+CD27+RBD+ memory B cells in these HLA-B*15 population compared to other cohorts. Importantly, generating lower concentrations of cross-reactive anti-XBB.1.16 Nab post-BA.5.2 infection caused HLA-B*15 individuals to be further infected by XBB.1.16 variant. Conclusions: Individuals carrying the HLA-B*15 allele respond better to COVID-19 vax including the CanSino Ad5-nCoV and the Sinovac CoronaVac inactivated vaccines, but are more susceptible to Omicron variant infection, thus, a novel vaccine against this population is necessary for COVID-19 pandemic control in the future. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is a newly identified tick-borne viral hemorrhagic fever caused by Dabie Banda virus (DBV). The virus was first discovered in eastern China in 2009 and is now considered an infectious disease with a mortality rate ranging from 6.3% to 30%. The best strategy for controlling SFTS is to develop effective vaccines. However, no approved vaccines are currently available to prevent this disease, despite the number of extensive and in-depth studies conducted on DBV in the past few years. This review focuses on the structure of DBV and the induced host immune responses which are the fundamental factors in vaccine development, and thoroughly summarizes the current research progress on DBV vaccines. The developing DBV vaccines include protein subunit vaccines, live attenuated vaccines, recombinant virus vector vaccines, and DNA vaccines. At present, almost all candidate vaccines for DBV are in the laboratory development or preclinical stages. There remain challenges in successfully developing clinically approved DBV vaccines. [ABSTRACT FROM AUTHOR]

Background: The emergence of nanotechnology has injected new vigor into vaccine research. Nanovaccine research has witnessed exponential growth in recent years; yet, a comprehensive analysis of related publications has been notably absent. Objective: This study utilizes bibliometric methodologies to reveal the evolution of themes and the distribution of nanovaccine research. Methods: Using tools such as VOSviewer, CiteSpace, Scimago Graphica, Pajek, R-bibliometrix, and R packages for the bibliometric analysis and visualization of literature retrieved from the Web of Science database. Results: Nanovaccine research commenced in 1981. The publication volume exponentially increased, notably in 2021. Leading contributors include the United States, the Chinese Academy of Sciences, the "Vaccine", and researcher Zhao Kai. Other significant contributors comprise China, the University of California, San Diego, Veronique Preat, the Journal of Controlled Release, and the National Natural Science Foundation of China. The USA functions as a central hub for international cooperation. Financial support plays a pivotal role in driving research advancements. Key themes in highly cited articles include vaccine carrier design, cancer vaccines, nanomaterial properties, and COVID-19 vaccines. Among 7402 keywords, the principal nanocarriers include Chitosan, virus-like particles, gold nanoparticles, PLGA, and lipid nanoparticles. Nanovaccine is primarily intended to address diseases including SARS-CoV-2, cancer, influenza, and HIV. Clustering analysis of co-citation networks identifies 9 primary clusters, vividly illustrating the evolution of research themes over different periods. Co-citation bursts indicate that cancer vaccines, COVID-19 vaccines, and mRNA vaccines are pivotal areas of focus for current and future research in nanovaccines. "candidate vaccines," "protein nanoparticle," "cationic lipids," "ionizable lipids," "machine learning," "long-term storage," "personalized cancer vaccines," "neoantigens," "outer membrane vesicles," "in situ nanovaccine," and "biomimetic nanotechnologies" stand out as research interest. Conclusions: This analysis emphasizes the increasing scholarly interest in nanovaccine research and highlights pivotal recent research themes such as cancer and COVID-19 vaccines, with lipid nanoparticle-mRNA vaccines leading novel research directions. [ABSTRACT FROM AUTHOR]

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Comprehensive evaluation of reservoirs is an important link in gas reservoir exploration and development. The evaluation of tight carbonate reservoirs often focuses on the characteristics of porosity and permeability, ignoring the important factor of fractures, also the quantitative evaluation of reservoirs is relatively few. It is difficult to identify fractures and evaluate the reservoir factors qualitatively and quantitatively. Herein, the sedimentary microfacies and microporosity of the tight carbonate reservoir of the Ma55 submember in the eastern Sulige area are comprehensively studied by casting thin section, rock physical property, and capillary pressure test data. The backpropagation (BP) neural network algorithm is used to identify and predict fractures. Finally, through the analytic hierarchy process, the above reservoir influencing factors are modeled and quantitatively analyzed for reservoir evaluation. The results show that the highest probability of fracture development in the central and northwest areas of the study area can reach 0.92. The accuracy of the BP neural network model in identifying cracks can reach 80%, which is reliable and effective compared with the conventional logging identification method. Reservoirs can be classified into four types according to their quality. The synthetic weights of porosity, permeability and fracture development probability are 0.2, 0.2 and 0.216 respectively, which are the three most important evaluation parameters. This study improves the accuracy of fracture identification and prediction of tight reservoirs in comprehensive reservoir evaluation, which provides guidance and scheme for more detailed exploration and development of tight carbonate reservoirs. [ABSTRACT FROM AUTHOR]

Background: This study aimed to enhance and improve the quality and safety of soy sauce. In the present work, the change of biogenic amines, such as histamine, tyramine, cadaverine, spermidine, was examined by the treatment of Candida versatilis and Zygosaccharomyces rouxii, and the influence of salt-tolerant yeast on biogenic amines was analysed during the whole fermentation process., Results: The results showed that the content of biogenic amines was elevated after yeast treatment and the content of biogenic amines was influenced by using yeast. The dominating biogenic amine in soy sauce was tyramine. At the end of fermentation, the concentrations of biogenic amines produced by Zygosaccharomyces rouxii and Candida versatilis in the soy mash were 122.71 mg kg(-1) and 69.96 mg kg(-1) ., Conclusions: The changes of biogenic amines in high-salt liquid soy mash during fermentation process indicated that a variety of biogenic amines were increased in the fermentation ageing period, which may be due to amino acid decarboxylation to form biogenic amines by yeast decarboxylase. The fermentation period of soy sauce should be longer than 5 months because biogenic amines began to decline after this time period., (© 2013 Society of Chemical Industry.)

Objective: To observe the influence of electroacupuncture (EA) on serum ghrelin content and bone mineral density in ovariectomized (OVX) rats so as to explore its mechanism underlying improvement of postmenopausal osteoporosis., Methods: Thirty ovariectomized SD rats with osteoporosis were randomized into model, EA and estrogen groups (n = 10) and other 10 rats received sham operation were assigned to be control group. For OVX rats of the EA group, EA (2 Hz, 1-3 mA) was applied to "Sanyinjiao" (SP 6) + "Guanyuan" (CV 4) or "Shenshu" (BL 23) + "Housanli" (ST 36), alternately for 20 min, once daily for consecutive 3 months. For rats of the estrogen group, subcutaneous injection of estradiol benzoate (0.1 mg/kg) was given once a week for 3 months. The bone mineral density (BMD) of the lumbar vertebrae and femur were detected by using a bone densitometer, and serum ghrelin content was assayed by ELISA., Results: In comparison with the sham operation group, serum ghrelin level of the model group was significantly increased, and BMD of both lumbar vertebrae and femur were significantly decreased (P < 0.05). Compared with the model group, the serum ghrelin levels were considerably decreased in both EA group and estrogen group, while BMD levels were significantly upregulated in the EA and estrogen groups (P < 0.05). The effects of the EA group were obviously inferior to those of the estrogen group (P < 0.05)., Conclusion: Acupuncture intervention can improve bone density and lower serum ghrelin level in OVX rats, which may contribute to its effect in improving osteoporosis.

Sulfated polysaccharides have been known to inhibit proliferation in tumor cells. However, the molecular mechanisms involved in sulfated polysaccharides-induced apoptosis are still uncharacterized. In this study, the effect of a chemically sulfated polysaccharide obtained from Grifola frondosa (S-GFB) on HepG2 cell proliferation and apoptosis-related mechanism were investigated. It was found that S-GFB inhibited proliferation of HepG2 cells in a dose-dependent manner with IC50 at 48 h of 61 μg ml(-1). The results of scanning electron micrographs indicated that S-GFB induced typical apoptotic morphological feature in HepG2 cells. Flow cytometric analysis demonstrated that S-GFB caused apoptosis of HepG2 cells through cells arrested at S phase. Western-blotting results showed that S-GFB inhibited notch1 expression, IκB-α degradation and NF-κB/p65 translocation from cytoplasm into nucleus. Simultaneously, the apoptotic mechanism of HepG2 cells induced by S-GFB was associated with down regulation of FLIP, and activation of caspase-3 and caspase-8. Taken together, these findings suggest that the S-GFB induces apoptosis through a notch1/NF-κB/p65-mediated caspase pathway., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

Although Musca domestica larvae lectin (MLL) is able to inhibit cancer cell proliferation and to induce cancer cell apoptosis, the molecular mechanism(s) responsible for these processes remain elusive. In the current study, the signaling network underlying the MLL-induced apoptosis of human hepatoma BEL-7402 cell was investigated. Our data found out that MLL causes a sustained increase of the intracellular Ca(2+) and this process was prevented by the intracellular calcium chelator, BAPTA-AM, suggesting the involvement of intracellular Ca(2+) in MLL-induced cell apoptosis. MLL also causes the production of reactive oxygen species and elevates the phosphorylation status of JNK, processes associated with the increased cytoplasmic Ca(2+). The mitochondrial permeability transition pore (MPTP) opening study showed that MLL treatment of BEL-7402 cells results in the opening of MPTP and a reduction of mitochondrial transmembrane potential. In such condition, cytochrome-c was detected to be released from mitochondria to cytoplasm through the MPTP. This eventually activates caspase-3 and thus results in apoptosis of the tested BEL-7402 cells. According to a comprehensive review of all the evidence, it is concluded that MLL induces apoptosis of BEL-7402 cells through a Ca(2+)/JNK-mediated MPTP pathway.

Although surfactin is able to inhibit cancer cell proliferation and to induce cancer cell apoptosis, the molecular mechanism responsible for this process remain elusive. In this study, the signaling network underlying the apoptosis of human hepatoma (HepG2) cells induced by surfactin was investigated. It is found that the reaction oxygen species (ROS) production and intracellular calcium ([Ca(2+)]i) accumulation are both induced HepG2 cells apoptosis. The [Ca(2+)]i exaltation was partly depended on the Ca(2+) release from inositol 1,4,5-trisphosphate (IP3) and ryanodine (Ry) receptors channels, which both triggered endoplasmic reticulum stress (ERS). The results showed that surfactin induced the ROS production and ROS production led to ERS. The occurrence of ERS increased the [Ca(2+)]i level and the processes associated with blocking extracellular signal-regulated kinase (ERK) pathway. According to a comprehensive review of all the evidence, it is concluded that surfactin induces apoptosis of HepG2 cells through a ROS-ERS-Ca(2+) mediated ERK pathway.

This study was aimed to explore the change of single nucleotide polymorphism (SNP) of thrombin-activatable fibrinolysis inhibitor (TAFI) and its correlation of 2 sites (505a/g, 1040c/t) in its gene-coding region with venous thromboembolism (VTE). The genotype distribution of TAFI in 80 patients with VTE and 80 normal controls was detected by allele-specific PCR. The results showed that the distribution of each genotype of 505a/g polymorphism was not significantly different between the VTE and control groups (P > 0.05). However, t allele frequency of 1040c/t in VTE group decreased significantly as compared with the control group (40% vs 53.75%, P < 0.05), mainly due to the decrease of the proportion of tt homozygous in VTE group. It is concluded that obvious relationship is found between the polymorphism of 1040c/t in TAFI gene and VTE patients. t allele genotype may paly a protective role in VTE. The polymorphism of TAFI 505a/g may be not associated with VTE.

NH(3) is a structural analogue of substrate H(2)O and an inhibitor to the water oxidation reaction in photosystem II. To test whether or not NH(3) is able to replace substrate water molecules on the oxygen-evolving complex in photosystem II, we studied the effects of NH(3) on the high-frequency region (3750-3550 cm(-1)) of the S(2)Q(A)(-)/S(1)Q(A) FTIR difference spectra (pH 7.5 at 250 K), where OH stretch modes of weak hydrogen-bonded active water molecules occur. Our results showed that NH(3) did not replace the active water molecule on the oxygen-evolving complex that gave rise to the S(1) mode at ~3586 cm(-1) and the S(2) mode at ~3613 cm(-1) in the S(2)Q(A)(-)/S(1)Q(A) FTIR difference spectrum of PSII. In addition, our mid-frequency FTIR results showed a clear difference between pH 6.5 and 7.5 on the concentration dependence of the NH(4)Cl-induced upshift of the S(2) state carboxylate mode at 1365 cm(-1) in the S(2)Q(A)(-)/S(1)Q(A) spectra of NH(4)Cl-treated PSII samples. Our results provided strong evidence that NH(3) induced this upshift in the spectra of NH(4)Cl-treated PSII samples at 250 K. Moreover, our low-frequency FTIR results showed that the Mn-O-Mn cluster vibrational mode at 606 cm(-1) in the S(2)Q(A)(-)/S(1)Q(A) spectrum of the NaCl control PSII sample was diminished in those samples treated with NH(4)Cl. Our results suggest that NH(3) induced a significant alteration on the core structure of the Mn(4)CaO(5) cluster in PSII. The implication of our findings on the structure of the NH(3)-binding site on the OEC in PSII will be discussed.

Objective: To investigate the impact of protein kinase B (Akt2) allele deletion on testicular reproductive function, and to discuss the regulatory effect of Cryptotanshinone on the reproductivity of male mice with Akt2 allele deletion and its molecular mechanism., Methods: Fifteen Akt2 +/+ male mice were randomly divided into Groups A (baseline control, n = 7) and B (stimulation, n = 8), and another 29 Akt2 -/- male mice into C (baseline control, n = 7), D (stimulation, n = 8), E (solvent, n = 7) and F (Cryptotanshinone, n = 7). Groups B and D underwent human chorionic gonadotropin (HCG) stimulation tests at 5 IU / 20 g, while A and C received physiological saline, all for 4 hours; Group F were given gastric lavage of Cryptotanshinone, while E solvent only, at 600 mg/kg twice a day for 8 weeks, both subjected to oral glucose tolerance tests (OGTT) at 2 g/kg before and after the treatment. The body and bilateral testis weights were obtained, the serum testosterone (T) level measured, and the expressions of testicular steroid hormone synthesis and glycometabolism-related genes determined by RT-PCR., Results: OGTT showed that the level of blood glucose was significantly higher in Groups C and D than in A and B ([10.38 +/- 1.42] and [10.96 +/- 1.81] mmol/L vs [7.92 +/- 0.63] and [8.32 +/- 0.44] mmol/L, P < 0.05), but had no significant differences at different time points in E and F (P > 0.05). The testis weight was remarkably higher in Groups C and D than in A and B ([0.17 +/- 0.01] and [0.17 +/- 0.01] g vs [0.15 +/- 0.01] and [0.15 +/- 0.02] g, P < 0.05), but exhibited no obvious difference in E and F, nor were there any significant differences in body weight among different groups (P > 0.05). The serum T level was markedly higher in Group C than in A ([9.08 +/- 1.59] nmol/L vs [6.42 +/- 0.95] nmol/L, P < 0.05), but evidently lower in F than in E ([5.94 +/- 0.49] nmol/L vs [8.18 +/- 1.44] nmol/L, P < 0.05). The baseline expression levels of Cyp11, Cyp17, 3B-HSD, Star, Gsk3beta, Erk-1, and MCM2 mRNA were significantly higher in Group C than in A (P < 0.05). After HCG stimulation, the expressions of Cyp11, Cyp17, 3B-HSD, and Star mRNA were remarkably increased in B and D, but with no obvious difference between the two groups (P > 0.05), while the expressions of Cyp11, Cyp17, 3B-HSD, Star, Gsk3beta, Erk-1, and MCM2 mRNA markedly decreased in F as compared with E (P < 0.05)., Conclusion: Akt2 gene deletion may affect glycometabolism and testicular function, and cause abnormal glycometabolism and androgen secretion in male mice, whose molecular mechanism is associated with the elevated expressions of the key glycometabolic molecules and of the key enzymes for androgen synthesis. Cryptotanshinone can reduce the levels of androgens by down-regulating the expressions of the key enzymes for androgen synthesis.

To understand the osmo-adaptation mechanism in Torulopsis versatilis (T), we investigated the salt-tolerant gene HOG1 from the wild-type and a salt-tolerant mutant strain (T5) constructed using genome shuffling. The HOG1 genes from T and T5 were sequenced and revealed several mutations had occurred. The expression level of T5HOG1 was stronger than that of THOG1, indicating a reason for the increase of salt-tolerance in T. versatilis. Moreover, overexpression of T5HOG1 and THOG1 improved the tolerance of salt in Saccharomyces cerevisiae. Identification and overexpression of THOG1 and T5HOG1 from the wild-type T. versatilis and the mutant T. versatilis, respectively, play an important role for the osmo-adaption mechanism of the T. versatilis used in soy-sauce fermentation.

This study was aimed to investigate the distribution of 1059 G/C gene polymorphism of C-reactive protein(CRP) in deep vein thrombus (DVT) and its clinical significance. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to screen 1059 G/C polymorphism in exon 2 of C-reactive protein gene in 61 cases of DVT and 60 healthy controls. The frequency of mutation was calculated. The results showed that there was no statistical difference of 1059 G/C genotype and mutation frequency of allele between deep vein thrombosis group and control group (p > 0.05). It is concluded that the 1059 G/C gene polymorphism of CRP displays certain difference in races and areas, and whether 1059 G/C gene polymorphism of CRP is a dangerous factor for deep vein thrombosis, which needs to be deeply explored.

The surfactin can inhibit proliferation and induce apoptosis in cancer cells. Moreover, surfactin can induce cell death in human breast cancer MCF-7 cells through mitochondrial pathway. However, the molecular mechanism involved in this pathway remains to be elucidated. Here, the reactive oxygen species (ROS) and Ca(2+) on mitochondria permeability transition pore (MPTP) activity, and MCF-7 cell apoptosis which induced by surfactin were investigated. It is found that surfactin evoked mitochondrial ROS generation, and the surfactin-induced cell death was prevented by N-acetylcysteine (NAC, an inhibitor of ROS). An increasing cytoplasmic Ca(2+) concentration was detected in surfactin-induced MCF-7 apoptosis, which was inhibited by 1,2-bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM, a chelator of calcium). In addition, the relationship between ROS generation and the increase of cytoplasm Ca(2+) was determined. The results showed that surfactin initially induced the ROS formation, leading to the MPTP opening accompanied with the collapse of mitochondrial membrane potential (ΔΨ(m)). Then the cytoplasmic Ca(2+) concentration increased in virtue of the changes of mitochondrial permeability, which was prevented by BAPTA-AM. Besides, cytochrome c (cyt c) was released from mitochondria to cytoplasm through the MPTP and activated caspase-9, eventually induced apoptosis. In summary, surfactin has notable anti-tumor effect on MCF-7 cells, however, there was no obvious cytotoxicity on normal cells., (2011 Elsevier Ireland Ltd. All rights reserved.)

Traditional Chinese medicine (TCM) usually views polycystic ovary syndrome (PCOS) as a menstrual disease or infertility disease. Reproductive dysfunction in PCOS is characterized by ovarian androgen excess and disturbance of follicular development, and its main clinical manifestations include delayed menstruation, scant menstruation, amenorrhea or infertility. Insulin resistance is a key pathological mechanism of PCOS. "Tiangui" (kidney essence) as a sex-stimulating essence in female in TCM theory, is essential to the menstruation and pregnancy of women. The disturbance of Tiangui (including time, status and rhythm) would result in female reproductive problems. Current studies of Tiangui indicate that ovary is the target organ of PCOS treatment, and its functional characteristics are consistent with the properties of Tiangui in time frame, state form and rhythm cycle. It is then concluded that ovarian dysfunction in PCOS can be expressed as disorder of Tiangui.

The role of killer Ig-like receptors (KIR) in SCT was analyzed. A total of 75 Chinese patients were transplanted with T-depleted hematopoietic stem cells from unrelated donors. Among the 75 donor-recipient pairs, 60 were HLA 10/10 matched and 15 had some mismatches at HLA-C. Transplants from KIR haplotype B/x group donors showed significantly higher overall survival rates compared with those from KIR haplotype A/A donors (relative risk (RR) 3.1 (95% confidence interval (CI) 1.1-8.6), P=0.007). In the haplotype A/A group, a higher risk of acute GVHD (aGVHD) (RR 9.0 (95% CI 1.2-66.9), P=0.01), especially grade III-IV aGVHD (P=0.006), was observed when the donor was homozygous for the full-length expressed KIR2DS4*00101 allele. Real-time PCR showed that a high expression of inhibitory KIR (2DL1 and 3DL1) in the early stages (<90 days) after transplantation correlated with the development of aGVHD (z=2.558, P=0.011). Our findings indicated a significant association of full-length KIR2DS4 or KIR2DL1/3DL1 expression with the occurrence of aGVHD. In aggregate these results suggested that combining KIR and HLA genotyping could help in the selection of transplant donors and improve the outcome of transplantation. Dynamic detection of KIR2DL1/3DL1 expression would be beneficial for prediction of aGVHD after transplantation.

Objective: To investigate the biological effect and mechanism of action of pseudolaric acid B (PAB) on the cultured human HeLa cells in vitro., Methods: MTT and flow cytometric assays were used to detect the cells proliferation inhibitory rate and apoptosis of HeLa cell in exposure to PAB; the morphological changes of apoptosis were observed with electron microscope; and the expressions of p53/bcl-2/bax mRNA were detected by RT-PCR., Results: (1) HeLa cell proliferation was inhibited by PAB in a dose-dependent manner, the IC50 being about 10 micromol/L; (2) flow cytometry showed that the distribution of HeLa cell cycle was changed time-dependently by 10 micromol/L PAB-treatment, showing decrease of G0/G1 phase cell percentage and increase of G2/M phase cell percentage; (3) the bax mRNA expression elevated and bcl-2 protein expression decreased markedly after being treated by 10 micromol/L PAB for 12 h, 24 h, and 48 h; while the expression of p53 mRNA could not be detected., Conclusion: PAB can inhibit the proliferation and induce the apoptosis of Hela cells in vitro, and its molecular mechanism may be associated with up-regulating bax mRNA expression and down-regulating bcl-2 mRNA expression.

This study was purposed to investigate the correlation of deep vein thrombosis (DVT) with C-reactive protein (CRP), fibrinogen (Fg), coagulation factor VIII (FVIII:C), coagulation factor IX (FIX:C) and to explore the effect of inflammation and coagulation as well as their interaction in DVT and its mechanism. 59 patients with DVT undergoing selective venous ultrasonography and 26 healthy individuals as controls were enrolled in this study. The plasma level of CRP was detected by immunoturbidimetry, FVIII:C, FIX:C levels were determined by a one-stage assay and fibrinogen level was measured by full-automatic biochemical apparatus. The results showed that the mean levels of plasma CRP, Fg, FVIII:C and FIX:C were significantly higher in deep vein thrombosis group than that in controls [CRP (2.67 +/- 0.91) vs (0.14 +/- 0.08) mg/dl; Fg (4.73 +/- 1.36) vs (2.79 +/- 0.66)g/L; FVIII:C (126.71 +/- 28.10) vs (81.35 +/- 20.77)%; FIX:C (81.01 +/- 23.60) vs (70.71 +/- 11.3)%] (p < 0.01), and the level of plasma CRP was strongly correlated with Fg, FVIII:C and FIX:C (r(s) = 0.432, 0.571 and 0.544, p < 0.01). It is concluded that the DVT and inflammation are closely related, increased level of plasma CRP may be a predictor of DVT. Increased plasma levels of Fg, FVIII:C and FIX:C all are important risk factors to DVT. Interaction between inflammation and coagulation promote the incidence of DVT, which may be one of DVT pathogenesis.

Flexible, or soft-shelled, eggs are almost unknown in the fossil record, leaving large gaps in our knowledge of the reproductive biology of many tetrapod clades. Here, we report two flexible-shelled eggs of the hyphalosaurid choristodere Hyphalosaurus baitaigouensis from the Early Cretaceous of China, one containing an embryo and the second associated with a neonate. Choristoderes are an enigmatic group of aquatic reptiles that survived the K-T extinction but died out in the Miocene. Hyphalosaurids, a specialized clade of Choristodera, resemble miniature plesiosaurs and are considered to be primarily aquatic in habit. Scanning electron microscopy of samples from the eggs reveals a thin, non-columnar external mineralized layer characterized by rounded nodes and tentatively identified poorly structured irregular pores, with an underlying amorphous layer presumably representing decomposed protein fibrils. While the relationships of Choristodera remain controversial, eggshell microstructure more closely resembles that of Lepidosauromorpha (the lineage including lizards) as opposed to that of Archosauromorpha (the lineage including birds and crocodiles).