A potential delivery system based on cholera toxin: A macromolecule carrier with multiple activities.

Macromolecular drugs are widely thought to be one of the most promising fields, but there are still many problems, especially with regard to drug delivery. Drug delivery systems are focused on loading efficiency without loss of activity, effective cellular internalization, anti-degradation, target ability, etc. New directions for macromolecular drugs delivery systems are not only to retain the activity of drugs, but bring new bioactivity to carry out dual benefits. Cholera toxin (CT) from Vibrio cholerae is one of such delivery systems and plays a potential role in delivering macromolecular drugs. After released from V. cholerae in the intestine, the B subunit of CT binds to the ganglioside GM1 on intestinal cells, and then the toxin gains access into the intestine. CT has potential as a "vaccine adjuvant-delivery system" (VADS) and is able to bring antigens and serve as adjuvants to induce specific immunity. In addition, it has been well used in the field of mucosal drug delivery and neural targeting. However, native CT is toxic, which restricts its practical application. There are several CT-based proteins with reduced virulence and reserved or even enhanced adjuvant activity under research. In this review, we comprehensively summarize the preparation strategy, advantages, applications and corresponding deficiencies of CT-based proteins. CT is focused on a delivery system when delivering macromolecular cargos such as active protein/peptide and antigen/antigen peptide. CT-based drug delivery system deserves further study due to their superiority.

Quantifying the Influence of Delay in Opinion Transmission of COVID-19 Information Propagation: Modeling Study.

BACKGROUND: In a fast-evolving public health crisis such as the COVID-19 pandemic, multiple pieces of relevant information can be posted sequentially on a social media platform. The interval between subsequent posting times may have a different impact on the transmission and cross-propagation of the old and new information that results in a different peak value and a final size of forwarding users of the new information, depending on the content correlation and whether the new information is posted during the outbreak or quasi-steady-state phase of the old information. OBJECTIVE: This study aims to help in designing effective communication strategies to ensure information is delivered to the maximal number of users. METHODS: We developed and analyzed two classes of susceptible-forwarding-immune information propagation models with delay in transmission to describe the cross-propagation process of relevant information. A total of 28,661 retweets of typical information were posted frequently by each opinion leader related to COVID-19 with high influence (data acquisition up to February 19, 2020). The information was processed into discrete points with a frequency of 10 minutes, and the real data were fitted by the model numerical simulation. Furthermore, the influence of parameters on information dissemination and the design of a publishing strategy were analyzed. RESULTS: The current epidemic outbreak situation, epidemic prevention, and other related authoritative information cannot be timely and effectively browsed by the public. The ingenious use of information release intervals can effectively enhance the interaction between information and realize the effective diffusion of information. We parameterized our models using real data from Sina Microblog and used the parameterized models to define and evaluate mutual attractiveness indexes, and we used these indexes and parameter sensitivity analyses to inform optimal strategies for new information to be effectively propagated in the microblog. The results of the parameter analysis showed that using different attractiveness indexes as the key parameters can control the information transmission with different release intervals, so it is considered as a key link in the design of an information communication strategy. At the same time, the dynamic process of information was analyzed through index evaluation. CONCLUSIONS: Our model can carry out an accurate numerical simulation of information at different release intervals and achieve a dynamic evaluation of information transmission by constructing an indicator system so as to provide theoretical support and strategic suggestions for government decision making. This study optimizes information posting strategies to maximize communication efforts for delivering key public health messages to the public for better outcomes of public health emergency management.

Unfolding the Determinants of COVID-19 Vaccine Acceptance in China.

BACKGROUND: China is at the forefront of global efforts to develop COVID-19 vaccines and has five fast-tracked candidates at the final-stage, large-scale human clinical trials testing phase. Vaccine-promoting policymaking for public engagement is a prerequisite for social mobilization. However, making an informed and judicious choice is a dilemma for the Chinese government in the vaccine promotion context. OBJECTIVE: In this study, public opinions in China were analyzed via dialogues on Chinese social media, based on which Chinese netizens' views on COVID-19 vaccines and vaccination were investigated. We also aimed to develop strategies for promoting vaccination programs in China based on an in-depth understanding of the challenges in risk communication and social mobilization. METHODS: We proposed a novel behavioral dynamics model, SRS/I (susceptible-reading-susceptible/immune), to analyze opinion transmission paradigms on Chinese social media. Coupled with a meta-analysis and natural language processing techniques, the emotion polarity of individual opinions was examined in their given context. RESULTS: We collected more than 1.75 million Weibo messages about COVID-19 vaccines from January to October 2020. According to the public opinion reproduction ratio (R0), the dynamic propagation of those messages can be classified into three periods: the ferment period (R01=1.1360), the revolution period (R02=2.8278), and the transmission period (R03=3.0729). Topics on COVID-19 vaccine acceptance in China include price and side effects. From September to October, Weibo users claimed that the vaccine was overpriced, making up 18.3% (n=899) of messages; 38.1% (n=81,909) of relevant topics on Weibo received likes. On the contrary, the number of messages that considered the vaccine to be reasonably priced was twice as high but received fewer likes, accounting for 25.0% (n=53,693). In addition, we obtained 441 (47.7%) positive and 295 (31.9%) negative Weibo messages about side effects. Interestingly, inactivated vaccines instigated more heated discussions than any other vaccine type. The discussions, forwards, comments, and likes associated with topics related to inactivated vaccines accounted for 53% (n=588), 42% (n=3072), 56% (n=3671), and 49% (n=17,940), respectively, of the total activity associated with the five types of vaccines in China. CONCLUSIONS: Most Chinese netizens believe that the vaccine is less expensive than previously thought, while some claim they cannot afford it for their entire family. The findings demonstrate that Chinese individuals are inclined to be positive about side effects over time and are proud of China's involvement with vaccine development. Nevertheless, they have a collective misunderstanding about inactivated vaccines, insisting that inactivated vaccines are safer than other vaccines. Reflecting on netizens' collective responses, the unfolding determinants of COVID-19 vaccine acceptance provide illuminating benchmarks for vaccine-promoting policies.

Morphologic and biochemical changes in the retina and sclera induced by form deprivation high myopia in guinea pigs.

BACKGROUND: To study the morphologic and biochemical changes in the retina and sclera induced by form deprivation high myopia (FDHM) in guinea pigs and explore the possible mechanisms of FDHM formation. METHODS: Forty 3-week-old guinea pigs were randomized into the blank control (Group I, 20 cases) and model groups (20 cases). In the model group, the right eyes of the guinea pigs were sutured for 8 weeks to induce FDHM (Group II) and the left eyes were considered a self-control group (Group III). The refractive errors were measured with retinoscopy. The anterior chamber depth (AC), lens thickness (L), vitreous chamber depth (V) and axial length (AL) were measured using ultrasonometry A. Retinal and scleral morphology and ultrastructural features were observed with light and electron microscopy. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the retina and sclera were detected with a chemical colorimetric assay. RESULTS: After 8 weeks of stitching, the refractive errors of Group II changed from (+ 3.59 ± 0.33) D to (- 7.96 ± 0.55) D, and these values were significantly higher than those of Group I (+ 0.89 ± 0.32) D and Group III (- 0.55 ± 0.49) D (P < 0.05). The vitreous chamber depth (4.12 ± 0.13) mm and axial length (8.93 ± 0.22) mm of Group II were significantly longer than those of Group I [(3.71 ± 0.23) mm and (7.95 ± 0.37) mm, respectively] and Group III [(3.93 ± 0.04) mm and (8.01 ± 0.15) mm, respectively] (P < 0.05). With the prolongation of form deprivation (FD), the retina and scleral tissues showed thinning, the ganglion cell and inner and outer nuclear layers of the retina became decreased, and the arrangement was disordered. In Group II, the SOD activity was significantly lower than that in Group I and Group III; the MDA content was significantly higher than that in Group I and Group III. The differences were statistically significant (P < 0.05). CONCLUSIONS: These findings suggested that in the FDHM guinea pigs model, the refractive errors, the vitreous chamber depth, and axial length increased significantly with prolongation of monocular FD time, and morphological structural changes in the retina and sclera were observed. Oxygen free radicals might participate in the formation of FDHM.

The effectiveness of olopatadine hydrochloride eye drops for allergic conjunctivitis: Protocol for a systematic review.

BACKGROUND: Allergic conjunctivitis (AC) is a multifactorial and common type of ocular surface disease that affects many people. The quality of life for AC patients can be significantly decreased caused by symptoms of ocular itching, swelling, redness, and tearing. Topical antihistaminics, mast cell stabilizers, non-steroidal anti-inflammatory drugs (NSAIDs), and steroids have been widely used to treat AC. Many clinical trials have indicated that olopatadine hydrochloride eye drops can provide quick relief of symptoms and signs. The purpose of this review is to evaluate systematically the effectiveness of olopatadine hydrochloride eye drops for treating AC. METHODS: A systematic review of all of the randomized controlled trials on the effectiveness and safety of olopatadine hydrochloride eye drops for AC will be conducted. We will search PubMed, Web of Science (WOS), EMBASE (OVID), the Cochrane Library, Google Scholar, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal database (VIP), Wanfang Database, and CBM, from the database inception date to October 31, 2019. There are no language or publication status restrictions. Registers of clinical trials, potential gray literature, reference lists of studies, and conference abstracts will also be searched. Two reviewers will independently read the articles, extract the data information, and assess the quality of the studies. Data will be synthesized by a heterogeneity test. The primary outcomes include the main symptom and sign scores before and after treatment, the eye redness index, the presence of eosinophils in the conjunctival scraping. Quality of life, the total treatment efficacy, and safety will be evaluated as the secondary outcomes. RevMan V.5.3 software will be used for the meta-analysis. RESULTS: The study will provide an objective and normative systematic review to evaluate the effectiveness and safety of olopatadine hydrochloride eye drops for the treatment of AC. CONCLUSION: Our review will provide useful information to judge whether olopatadine hydrochloride eye drops is an effective intervention for patients with AC. ETHICS AND DISSEMINATION: It is not necessary to obtain ethical approval as participants are not involved patients. The protocol and results will be published in a peer-reviewed journal. The systematic review will also be disseminated electronically and in print to help guide health care practice and policy. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019132232.

The effectiveness and safety of moxibustion for dry eye: Protocol for a systematic review.

BACKGROUND: Dry eye (DE) is a common type of ocular surface disease that affects many people. Moxibustion has been widely used in China to treat ocular surface diseases, especially DE. Many clinical trials have demonstrated that moxibustion can increase the tear secretion quantity and improve tear film stability. The purpose of this review is to provide an objective and normative systematic review to evaluate the effectiveness and safety of moxibustion treatment in patients with DE. METHODS: The systematic review will include all of the randomized controlled trials on the effectiveness and safety of moxibustion for DE. Nine medical databases, namely PubMed, EMBASE, the Cochrane Library, Google Scholar, Web of Science, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal database (VIP), Wanfang Database, and CBM, will be searched from the date of the database inception to February 28, 2019. We will also search registers of clinical trials, potential gray literature, and conference abstracts. There are no restrictions on language and publication status. Two reviewers will independently select studies, and extract and manage data. The reporting quality and risk of bias will be assessed by other 2 review authors. The primary outcomes will include ocular surface disease index (OSDI) scores, Schirmer test (SIT) results, tear meniscus height (TMH), and tear break-up time (TBUT) values. Quality of life, the main symptom scores before and after treatment, meibomian gland (MG) morphology, total treatment efficacy, and safety will be evaluated as the secondary outcomes. We will use RevMan V.5.3 software to synthesize and analyze data. RESULTS: This systematic review will provide a comprehensive review of current evidence of moxibustion for DE from the following aspects: the OSDI, SIT, TMH, BUT, quality of life, the main symptom scores, MG morphology, total treatment efficacy, and safety. CONCLUSION: The conclusion of our systematic review will provide evidence to determine whether moxibustion is an effective and safe intervention for patients with DE. ETHICS AND DISSEMINATION: Since patients will not be involved in this study, it is not necessary to obtain ethical approval. The protocol and results will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42018097399.

Functional and morphologic study of retinal hypoperfusion injury induced by bilateral common carotid artery occlusion in rats.

Retinal hypoperfusion injury is the pathophysiologic basis of ocular ischemic syndrome (OIS) which often leads to severe visual loss. In this study, we aimed to establish a rat model of retinal chronic hypoperfusion by bilateral common carotid artery occlusion (BCCAO) and observe changes in the retinal function and morphology. We found that model rats showed retinal arteriosclerosis, slight dilated retinal vein, small hemangiomas, hemorrhages, vascular segmental filling, and nonperfused areas after 2 weeks of BCCAO. In the model rats, the retinal circulation time was significantly prolonged by fluorescein fundus angiography (FFA), the latency of a and b waves was delayed and the amplitude was decreased significantly at each time point by electroretinogram (ERG), and the perfusion of the eyes continued to reduced. Morphologic and ultrastructural changes covered that the retinal ganglion cells (RGCs) presented obvious apoptosis and the thickness in the retinal layers were significantly thinner. Collectively, these findings suggested that BCCAO induced retinal hypoperfusion injury in the model rats, thus providing an ideal animal model for the study of OIS.

Safety of Qigong: Protocol for an overview of systematic reviews.

BACKGROUND: Qigong, as one of the essential elements of Traditional Chinese exercises, has been used to improve physical and psychological health and combat diseases in China for thousands of years. In recent years, the beneficial effects of Qigong on different medical conditions are becoming more accepted by both patients and health care providers. Although it is a common impression that Qigong and related therapies are generally safe procedures, but the current understanding of its adverse events is fragmented. Thus, we conducted this overview to synthesize comprehensively existing systematic reviews on adverse events associated with Qigong and related therapies, and our findings can be used to informing clinicians, Qigong practitioner, and patients alike on applying such treatments or interventions in clinical treatment and daily life training mindful manner, and provide a guideline for researchers in future. METHODS: A systematic review of reviews will be performed. A literature search strategy designed by a number of specialists in the fields of Traditional Chinese Medicine (TCM), sports medicine, health information, and Qigong training will be carried out in relevant English and Chinese electronic database. The date range of search will start from inception to the search date. Two reviewers will identify relevant studies, extract data information, and then assess the methodical quality by Assessment of Multiple Systematic Reviews (AMSTAR) tool. Any types of systematic review that summarized adverse effects related to Qigong and related therapies in human will be included. Any safety-related outcomes will be considered as the primary outcomes of this overview. Where objectives from 2 or more reviews overlap, we will assess the causes of any noted discrepancies between reviews. An overall summary of results will be performed using tabular and graphical approaches and will be supplemented by narrative description. RESULTS: This overview will identify any adverse events associated with nonstandardized Qigong and related therapies procedures based on current relevant literature evidence of safety for Qigong. CONCLUSION: Our overview will provide evidence to help synthesize the broad degree of information available on furthering the knowledge, safety, and application of Qigong. ETHICS AND DISSEMINATION: Formal ethical approval is not required, as this study is an overview based on the published systematic reviews. The result of this overview of systematic reviews will be published in a peer-reviewed journal or disseminated at national and international conferences. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42018109409.

The effect of Imaginary Working Qigong on the psychological well-being of college students: Study protocol for a randomized controlled trial.

INTRODUCTION: College students are special populations that are particularly prone to have significantly high level of psychological distress than their community peers. Apparently, the best way to manage stress and mental state is through self-care. The characteristic of Qigong is self-directed and self-healing, which is a traditional Chinese mind-body exercise, which has the potential as a stress management intervention. Imaginary Working Qigong, as a kind of static Qigong, is more perception-oriented and can bring about benign sensations of mind and body so as to eliminate stress completely and induce physiological and mental relaxation. In this study protocol, we will systematically examine the feasibility and acceptability of Imaginary Working Qigong on psychological outcomes of the college students and deeply explore molecular biological mechanisms underlying the effects of mind adjustment induced Imaginary Working Qigong. METHODS/DESIGNS: We will conduct a randomized, assessor and statistician-blinded, parallel-controlled trial exploring the beneficial mind adjustment of Imaginary Working Qigong in college students.A total of 80 eligible college students from Beijing University of Chinese Medicine will be recruited and randomly allocated into Imaginary Working Qigong training or unaltered lifestyle control group according 1:1 allocation ratio with allocation concealment. Imaginary Working Qigong training will last 8 weeks. The study period is 12 weeks including a 4-week supervised training, 4-week independence training, and a 4-week follow-up. Relevant psychological outcomes measurement will take place at baseline, 5 weeks (at the end of supervised training), 9 weeks (at the end of independence training), and 13 weeks (after the 4-week follow-up period) by blinded independent outcome assessors. CONCLUSION: This is the first randomized controlled trial protocol from the perspective of Qigong connotation to systematically evaluate the effects and relevant molecular mechanism of Imaginary Working Qigong for the mental health of a college student population. If our study demonstrates a significant intervention effect, this would provide preliminary higher-quality evidence and establish a further guidance for the application of Imaginary Working Qigong program among a college student population. ETHICS AND DISSEMINATION: The study protocol and consent forms have been approved by the medical and animal experiment ethic committee of BUCM (approval number: BJZYYDX-LL2014005).

Effect of Liuzijue Qigong on patients with chronic obstructive pulmonary disease: Protocol for a systematic review and meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide with a substantial and increasing social and economic burden. Liuzijue Qigong is a kind of traditional Chinese Qigong exercises that Traditional Chinese Medicine practitioners prescribe to individuals with COPD to strengthen the internal organs' function. Liuzijue Qigong was recommended for use in COPD rehabilitation, and some clinical trials indicate that Liuzijue Qigong would produce better functional capacity and quality of life of individuals with COPD. The objective of this study is to conduct a systematic review of the existing studies to assess effectiveness and safety of Liuzijue Qigong for the prevention or treatment of COPD in patients. METHODS: We will perform the comprehensive literature search in English and Chinese electronic database. The publication period will be from inception to the search date. In addition, the clinical trial registries, dissertations, informal publication, grey literature, reference lists of studies, systematic reviews, and conference abstracts will also be collected. Two reviewers will identify relevant studies, extract data information, and then assess the methodical quality by the Cochrane risk of bias assessment tool. Only randomized controlled trials comparing Liuzijue Qigong against other intervention or nonintervention will be included. Data will be synthesized by either fixed-effect or random-effect model regarding to a heterogeneity test. The routine lung function, arterial blood gas tensions, partial pressure of carbon dioxide, functional capacity, 30 seconds sit-to-stand test, respiratory function, maximal inspiration pressure, maximal expiratory pressure, airway resistance, and specific airway conductance will be assessed as primary outcomes. The secondary outcomes involved dyspnea, and fatigue levels, respiratory muscle strength, upper and lower limb muscle strength, handgrip strength test, and health-related quality of life and safety. Meta-analysis will be performed by using Cochrane's Review Manager software (version 5.3.5). RESULTS: This systematic review and meta-analysis will provide a high-quality synthesis and evaluate the efficacy and safety based on current relevant literature evidence of Liuzijue Qigong intervention for COPD patient. CONCLUSION: Our systematic review will provide evidence to determine whether Liuzijue Qigong is an effective and safe approach to prevention and treatment of COPD patients.

Acupuncture for ophthalmoplegia: Protocol for a systematic review.

BACKGROUND: Ophthalmoplegia is a disease that affects many people every year and is caused by reasons, such as cavernous sinus lesion, intracranial aneurysm, diabetes, and trauma. Acupuncture has been widely used to treat ophthalmological diseases especially ophthalmoplegia in China. Many clinical trials indicate that acupuncture may promote the recovery of extraocular muscles in ophthalmoplegia patients. We aim to conduct a meta-analysis to evaluate the efficacy and safety of acupuncture for ophthalmoplegia. METHODS: We will retrieve the literature from the following electronic databases, by March 31, 2018, such as PubMed, EMBASE, the Cochrane Library, Web of Science database, Chinese BioMedical Literature Database, China National Knowledge Infrastructure, China Science and Technology Journal database, and Wanfang Database. We will also collect clinical trial registries, dissertations, grey literature, reference lists of studies, systematic reviews, and conference abstracts. Two people will review these articles, extract the data information, and assess the quality of studies separately. Data will be synthesized by either fixed-effects or random-effects model regarding to a heterogeneity test. The eyeball movement distance, size of fissure palpebrae, and the reduced degree of strabismus will be assessed as the primary outcomes. The secondary outcomes will be the size of the pupil, main symptom scores, ocular localization analysis, and functional impairment extent and safety. We will use the specific software called RevMan (version 5.3) to perform the meta-analysis. RESULTS: This study will provide a high-quality synthesis based on current evidence of acupuncture for ophthalmoplegia, especially its impacts on eyeball movement distance, size of fissure palpebrae, the reduced degree of strabismus, size of the pupil, main symptom scores, ocular localization analysis, and functional impairment extent and safety. EXPECTED CONCLUSION: Our systematic review will provide evidence to determine whether acupuncture is an effective and safe intervention for ophthalmoplegia patients. ETHICS AND DISSEMINATION: It is not necessary for this systematic review to acquire an ethical approval. This review will be disseminated in a peer-reviewed journal or conference presentation. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42018091536.

[Distribution of Press-sensitive Acupoints in Patients with Tinnitus].

OBJECTIVE: To explore the regularity of distribution of press-sensitive acupoints on the body surface in tinnitus patients, so as to provide evidence for selecting suitable acupuncture points in the treatment of tinnitus. METHODS: Sixty-three cases of tinnitus patients (from 25 to 75 years in age) were recruited in the present study. The patient was asked to take a sitting, supine and prone position, successively, and the operator used the thumb to moderately press the subject's head, neck, back, four limbs below the knee- and elbow joints along the three Hand- and three Foot-yang and yin meridians. Those acupoints that appeared pressing pain, or soreness-distension, numbness, or radiation feeling more than 10 times were brought into the sequence analysis by using the Excel 2010. RESULTS: A total of 131 press-sensitive acupoints including 41 points with an appea-rance frequency of more than 10 times were found in the 63 tinnitus patients. These 41 acupoints distributing in the top three meri-dians were the Gallbladder Meridian of Foot-Shaoyang, Tri-energizer Meridian of Hand-Shaoyang and Spleen Meridian of Foot-Taiyin, and their involved regions were those below the knee-joints, bilateral sides of the head and marginal portion of the ear, sites bellow the elbow-joints, back-waist, successively in the appearance frequency. The top ten acupoints are Wangu (GB 12), Yifeng (SJ 17), Waiguan (SJ 5), Quchi (LI 11), Sanyinjiao (SP 6), Yanglingquan (GB 34), Fengchi (GB 20), Taichong (LR 3), Shousanli (LI 10) and Zulinqi (GB 41), in sequence. CONCLUSIONS: The press-sensitive acupoints in tinnitus patients distribute principally in the Gallbladder Meridian of Foot-Shaoyang, and below the knee-joint, and the most sensitive acupoints are Wangu (GB 12) and Yifeng (SJ 17). These findings may provide an objective basis for clinical diagnosis and treatment of tinnitus.