Reconstructing 3D digital model without distortion for poorly conductive porous rock by nanoprobe-assisted FIB-SEM tomography.

Oil and natural gas prospecting requires precise pore characterisation of insulating rock samples, which involves severe charging problems in the state-of-art FIB-SEM tomography, such as overexposure, drift and distortion. For weak cemented samples with very poor conductivity, the conventional ways such as decreasing accelerating voltage or current as well as coating a thin layer of carbon or gold fail to eliminate all the detrimental effect, leading to image distortion in the form of lateral shift and longitudinal stretching. A new nanoprobe-assisted method is explored in FIB-SEM tomography to address this problem and improve image quality. To be specific, a metallic nanoprobe is induced and attached on the sample surface to create an express path for the export of excess electrons near the region of interest, which effectively removes distortion and drift when imaging. Two adjacent areas were characterised and reconstructed into 3D digital models by FIB-SEM tomography with nanoprobe-assisted method applied to one region only. The lateral shift creates zigzag feature for distorted region and the longitudinal stretching of undistorted object can reach 14%. Average pore size of distorted region is larger than that of the undistorted region, however considering the longitudinal stretching, the average pore size of distorted region can be corrected to the same level as the undistorted region. The systematic error caused by distortion for poorly conductive porous rock is hazardous for digital rock physics analysis. Therefore, the nanoprobe-assisted FIB-SEM tomography should be regarded as a one of the optional and feasible procedures in case decreasing accelerating voltage or current as well as coating a thin layer of conductive material does not work.

Image distortion caused by charging problems influence quantitative analysis and simulation, which is more serious in FIB-SEM tomography. This study is used to correct image distortion and reconstruct 3D digital model for poorly conductive samples such as porous rock by nanoprobe-assisted method applied in FIB-SEM tomography. A metallic nanoprobe is induced and attached on the sample surface to removes distortion and drift when imaging. By comparing two adjacent areas with nanoprobe-assisted method applied for one region only, the degree of distortion and pore size distributions are analysed and computed. We observe and analyse lateral shift creates zigzag feature for distorted region and the longitudinal stretching of undistorted object. The average pore size of distorted region is higher than undistorted region, which can be corrected considering the longitudinal stretching. Such systematic error caused by distortion for poorly conductive porous rock is hazardous for not only digital rock physics analysis but also research of unconductive materials. Therefore, the nanoprobe-assisted FIB-SEM tomography should be regarded as a one of the optional and feasible procedures in case decreasing accelerating voltage or current as well as coating a thin layer of conductive material does not work.

Effect of Long-Term Aging on Fatigue and Thermal Cracking Performance of Polyphosphoric Acid and Styrene-Butadiene-Styrene-Modified Bio-Blend Bitumen.

Polyphosphoric acid (PPA) and styrene-butadiene-styrene (SBS) were adopted to produce PPA-SBS-modified bio-blend bitumen, which achieved excellent mechanical performance. However, its long-range performance, such as the fatigue and thermal cracking behavior under long-term thermal oxidation, is not well understood. Therefore, a pressure aging vessel (PAV) system was applied to simulate the aging behavior of the bitumen under the action of thermal oxidation. Then, a linear amplitude sweep (LAS) test combined with a viscoelastic continuum damage (VECD) model was applied to investigate the fatigue properties of the bitumen. Moreover, a bending beam rheometer (BBR) test was conducted to evaluate the thermal cracking resistance of the bitumen before and after PAV aging. Meanwhile, an atomic force microscope (AFM) was applied to observe the microscopic topography. The results show that the original compound-modified bitumen can bear more fatigue damage than that of the control bitumen at the failure point, and it also has excellent fatigue resistance at 2.5%, 5%, 7.5%, and 10% applied strain. Moreover, the VECD model can accurately predict the fatigue life of the bitumen under different applied strains. The variation ratio of stiffness modulus for the compound-modified bitumen is below that of the control bitumen after PAV aging, so it shows a better anti-aging performance. Finally, the AFM test shows that PPA and bio-bitumen decrease the heterogeneity of the bitumen, reducing the difference between phases.

Different characteristics of striatal resting-state functional conectivity in treatment-resistant and non-treatment-resistant depression.

Major depressive disorder is associated with a reward deficit manifested by abnormal striatal function. However, differences between treatment-resistant depression (TRD) and non TRD (nTRD) in striatal whole-brain functional connectivity (FC) have not been elucidated. Thirty-eight patients with TRD, 42 patients with nTRD, and 39 healthy controls (HCs) were recruited for this study. A seed-based FC approach was used to analyze abnormalities in six predefined striatal subregion circuits in the three groups of subjects, and further explore the correlation between abnormal FC and clinical symptoms. Results revealed that compared with the nTRD group, the TRD group showed increased FC of the inferior ventral striatum with the bilateral orbital area of the middle frontal gyrus, right cerebellum posterior lobe, left parahippocampal gyrus, left middle occipital gyrus and left lingual gyrus. Compared with the HC group, the TRD group showed a wider range of altered striatal function than the nTRD group. In the TRD group, the HAMD-17 scores were positively correlated with the FC between the right VRP and the left caudate. This study provides new insights into understanding the specificity of TRD striatal circuits.

Distinct patterns of functional brain network integration between treatment-resistant depression and non treatment-resistant depression: A resting-state functional magnetic resonance imaging study.

BACKGROUND: Previous neuroimaging has paid little attention to the differences in brain network integration between patients with treatment-resistant depression(TRD) and non-TRD (nTRD), and the relationship between their impaired brain network integration and clinical symptoms has not been elucidated. METHOD: Eighty one major depressive disorder (MDD) patients (40 in TRD, 41 in nTRD) and 40 healthy controls (HCs) were enrolled for the functional magnetic resonance imaging (fMRI) scans. A seed-based functional connectivity (FC) method was used to investigate the brain network abnormalities of default mode network (DMN), affective network (AN), salience network (SN) and cognitive control network (CCN) for the MDD. Finally, the correlation was analyzed between the abnormal FCs and 17-item Hamilton Rating Scale for Depression scale (HAMD-17) scores. RESULTS: Compared with the HC group, the FCs in DMN, AN, SN, CCN were altered in both the TRD and nTRD groups. Compared with the nTRD group, FC alterations in the AN and CCN were more abnormal in the TRD group, and the FC alterations were generally decreased at the SN in the TRD group. In addition, the FC values of right dorsolateral prefrontal cortices and left caudate nucleus in the TRD group and the FC values of right subgenual anterior cingulate cortex and left middle temporal gyrus in the nTRD group were positively correlated with HAMD-17 scale scores. CONCLUSIONS: Abnormal FCs are present in four brain networks (DMN, AN, SN, CCN) in both the TRD and nTRD groups. Except of DMN, FCs in AN, SN and CCN maybe underlay the neurobiological mechanism in differentiating TRD from nTRD.

Neuroimaging mechanisms of acupuncture on functional reorganization for post-stroke motor improvement: a machine learning-based functional magnetic resonance imaging study.

Objective: Motor recovery is crucial in stroke rehabilitation, and acupuncture can influence recovery. Neuroimaging and machine learning approaches provide new research directions to explore the brain functional reorganization and acupuncture mechanisms after stroke. We applied machine learning to predict the classification of the minimal clinically important differences (MCID) for motor improvement and identify the neuroimaging features, in order to explore brain functional reorganization and acupuncture mechanisms for motor recovery after stroke. Methods: In this study, 49 patients with unilateral motor pathway injury (basal ganglia and/or corona radiata) after ischemic stroke were included and evaluated the motor function by Fugl-Meyer Assessment scores (FMA) at baseline and at 2-week follow-up sessions. Patients were divided by the difference between the twice FMA scores into one group showing minimal clinically important difference (MCID group, n = 28) and the other group with no minimal clinically important difference (N-MCID, n = 21). Machine learning was performed by PRoNTo software to predict the classification of the patients and identify the feature brain regions of interest (ROIs). In addition, a matched group of healthy controls (HC, n = 26) was enrolled. Patients and HC underwent magnetic resonance imaging examination in the resting state and in the acupuncture state (acupuncture at the Yanglingquan point on one side) to compare the differences in brain functional connectivity (FC) and acupuncture effects. Results: Through machine learning, we obtained a balance accuracy rate of 75.51% and eight feature ROIs. Compared to HC, we found that the stroke patients with lower FC between these feature ROIs with other brain regions, while patients in the MCID group exhibited a wider range of lower FC. When acupuncture was applied to Yanglingquan (GB 34), the abnormal FC of patients was decreased, with different targets of effects in different groups. Conclusion: Feature ROIs identified by machine learning can predict the classification of stroke patients with different motor improvements, and the FC between these ROIs with other brain regions is decreased. Acupuncture can modulate the bilateral cerebral hemispheres to restore abnormal FC via different targets, thereby promoting motor recovery after stroke. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=37359, ChiCTR1900022220.

Filiform needle acupuncture for allergic rhinitis: A systematic review and meta-analysis.

BACKGROUND: Filiform needle acupuncture (FNA), the most classical and widely applied acupuncture method based on traditional Chinese medicine theory, has shown a promising effect in the treatment of allergic rhinitis (AR). OBJECTIVE: To evaluate the efficacy, safety, cost-effectiveness, and patient preference of FNA in the treatment of AR by comparing FNA with sham acupuncture, no treatment, and conventional medication. SEARCH STRATEGY: Eight electronic databases were systematically searched from inception to October 14, 2021. Additional studies were acquired from clinical trial registration platforms and reference lists. INCLUSION CRITERIA: Randomized controlled trials were included if they compared FNA with either sham acupuncture, no treatment or conventional medication for AR. DATA EXTRACTION AND ANALYSIS: Two researchers extracted data independently of each other using a predesigned data acquisition form, and results were cross-checked after completion. The primary outcome was symptom score (Total Nasal Symptom Score or Visual Analogue Scale), and the secondary outcomes were the AR control questionnaire, quality of life (QoL) score (Different versions of Rhinoconjunctivitis Quality of Life Questionnaire), medication score (use of rescue medication), mental health score, total IgE, adverse event rate, clinical economic indicators, and patient satisfaction score. Standardized mean difference (SMD) or mean difference (MD) with 95% confidence interval was used to calculate the effect size for continuous data, while risk ratio with 95% CI was used for dichotomous data. RESULTS: Thirty studies were included in this review. Compared with sham acupuncture, FNA significantly reduced the symptom score (SMD: -0.29 [-0.43, -0.15]), AR's impact on QoL (SMD: -0.23 [-0.37, -0.08]) and medication score (SMD: -0.3 [-0.49, -0.11]). Compared with no treatment, FNA dramatically reduced the symptom score (SMD: -0.8 [-1.2, -0.39]) and AR's impact on QoL (SMD: -0.82 [-1.13, -0.52]). There were no increased rates of adverse events with FNA compared to sham acupuncture and no treatment. FNA increased patient satisfaction and may be cost-effective. Most pieces of evidence from the above two comparisons were of high confidence. Moreover, FNA significantly outperformed conventional medication in reducing the symptom score (SMD: -0.48 [-0.85, -0.1]) and displayed a lower rate of adverse events, but the quality of evidence was very low. CONCLUSION: FNA is an effective and safe intervention for AR and can help with symptom relief, QoL improvement, reducing medication usage, and increasing patient satisfaction. Further studies are needed to verify its cost-effectiveness and superiority over conventional medication and the best therapeutic strategies.

Characterization of Resting-State Striatal Differences in First-Episode Depression and Recurrent Depression.

The presence of reward deficits in major depressive disorder is associated with abnormal striatal function. However, differences in striatal whole-brain functional between recurrent depressive episode (RDE) and first-episode depression (FDE) have not been elucidated. Thirty-three patients with RDE, 27 with FDE, and 35 healthy controls (HCs) were recruited for this study. A seed-based functional connectivity (FC) method was used to analyze abnormalities in six predefined striatal subregion circuits among the three groups of subjects and to further explore the correlation between abnormal FC and clinical symptoms. The results revealed that compared with the FDE group, the RDE group showed higher FC of the striatal subregion with the left middle occipital gyrus, left orbital area of the middle frontal gyrus, and bilateral posterior cerebellar gyrus, while showing lower FC of the striatal subregion with the right thalamus, left inferior parietal lobule, left middle cingulate gyrus, right angular gyrus, right cerebellum anterior lobe, and right caudate nucleus. In the RDE group, the HAMD-17 scores were positively correlated with the FC between the left dorsal rostral putamen and the left cerebellum posterior lobe. This study provides new insights into understanding the specificity of striatal circuits in the RDE group.

Altered Brain Function in First-Episode and Recurrent Depression: A Resting-State Functional Magnetic Resonance Imaging Study.

Background: Studies on differences in brain function activity between the first depressive episode (FDE) and recurrent depressive episodes (RDE) are scarce. In this study, we used regional homogeneity (ReHo) and amplitude of low-frequency fluctuations (ALFF) as indices of abnormal brain function activity. We aimed to determine the differences in these indices between patients with FDE and those with RDE, and to investigate the correlation between areas of abnormal brain function and clinical symptoms. Methods: A total of 29 patients with RDE, 28 patients with FDE, and 29 healthy controls (HCs) who underwent resting-state functional magnetic resonance imaging were included in this study. The ReHo and ALFF measurements were used for image analysis and further analysis of the correlation between different brain regions and clinical symptoms. Results: Analysis of variance showed significant differences among the three groups in ReHo and ALFF in the frontal, parietal, temporal, and occipital lobes. ReHo was higher in the right inferior frontal triangular gyrus and lower in the left inferior temporal gyrus in the RDE group than in the FDE group. Meanwhile, ALFF was higher in the right inferior frontal triangular gyrus, left anterior cingulate gyrus, orbital part of the left middle frontal gyrus, orbital part of the left superior frontal gyrus, and right angular gyrus, but was lower in the right lingual gyrus in the RDE group than in the FDE group. ReHo and ALFF were lower in the left angular gyrus in the RDE and FDE groups than in the HC group. Pearson correlation analysis showed a positive correlation between the ReHo and ALFF values in these abnormal areas in the frontal lobe and the severity of depressive symptoms (P < 0.05). Abnormal areas in the temporal and occipital lobes were negatively correlated with the severity of depressive symptoms (P < 0.05). Conclusion: The RDE and FDE groups had abnormal neural function activity in some of the same brain regions. ReHo and ALFF were more widely distributed in different brain regions and had more complex neuropathological mechanisms in the RDE group than in the FDE group, especially in the right inferior frontal triangular gyrus of the frontal lobe.

Immediate Modulation of Transcutaneous Auricular Vagus Nerve Stimulation in Patients With Treatment-Resistant Depression: A Resting-State Functional Magnetic Resonance Imaging Study.

Background: Previous studies found that transcutaneous auricular vagus nerve stimulation (taVNS) was clinically effective in treating a case of treatment-resistant depression (TRD). However, the brain neural mechanisms underlying the immediate effects of taVNS treatment for TRD have not been elucidated. Materials and Methods: Differences in the amplitude of low-frequency fluctuations (ALFF) between TRD and healthy control (HC) groups were observed. The TRD group was treated with taVNS for 30 min, and changes in ALFF in the TRD group before and after immediate treatment were observed. The ALFF brain regions altered by taVNS induction were used as regions of interest to analyze whole-brain functional connectivity (FC) changes in the TRD group. Results: A total of 44 TRD patients and 44 HCs completed the study and were included in the data analysis. Compared with the HC group, the TRD group had increased ALFF in the left orbital area of the middle frontal gyrus. After taVNS treatment, ALFF in the left orbital area of the middle frontal gyrus and right middle frontal gyrus decreased in the TRD group, while ALFF in the right orbital area of the superior frontal gyrus increased. The FC in the left orbital area of the middle frontal gyrus with left middle frontal gyrus and the right inferior occipital gyrus was significantly increased. Conclusion: Transcutaneous auricular vagus nerve stimulation demonstrates immediate modulation of functional activity in the emotional network, cognitive control network, and visual processing cortex, and may be a potential brain imaging biomarker for the treatment of TRD.

A Study of Differential Resting-State Brain Functional Activity in Males and Females with Recurrent Depressive Disorder.

In this study, we observed the sex differences in functional brain activity in patients with recurrent depressive disorder (RDE) and assessed the correlation between abnormal functional brain activity changes and clinical symptoms. A total of 40 patients with RDE (19 male and 21 female) and 42 healthy controls (HCs) (20 male and 22 female) met the inclusion criteria. Analysis of images using regional homogeneity (ReHo) and further analysis of the correlation between abnormal brain areas and clinical symptoms of the different sexes with RDE groups were carried out. For the main effects of sex (male vs. female), there were statistically significant differences in ReHo among the four groups in the right middle temporal gyrus, right thalamus, and left posterior cerebellar lobe. For the effects of the sex-by-group interaction, there were statistically significant differences in ReHo among the four groups in the left middle frontal gyrus, left precentral gyrus, and right insula. Post hoc analyses showed that compared with the female RDE group, the male RDE group had decreased ReHo in the left middle frontal gyrus and right insula. In the female RDE group, the ReHo values of the left middle frontal gyrus were positively correlated with the 17-item Hamilton Rating Scale for Depression (HAMD-17) scores. This study provides new insights into the clinical targeting of different sexes for RDE.

Sex Differences of the Functional Brain Activity in Treatment-Resistant Depression: A Resting-State Functional Magnetic Resonance Study.

The presence of different clinical symptoms in patients with treatment-resistant depression (TRD) of different sexes may be related to different neuropathological mechanisms. A total of 16 male patients with TRD, 18 female patients with TRD, 18 male healthy controls (HCs) and 19 female HCs completed this study. We used the amplitude of low frequency fluctuations (ALFF) method to analyze the results. Moreover, the correlation between abnormal brain areas and clinical symptoms in different sexes of the TRD groups was also analyzed. The effects of the sex-by-group interaction difference in ALFF among the four groups was located in the left middle frontal gyrus, left precentral gyrus and left precuneus. Post hoc comparisons revealed that the male TRD group had lower ALFF in the left middle frontal gyrus and left precentral gyrus compared with the female TRD group. There was a positive correlation between the left middle frontal gyrus, the left precuneus and the 17-item Hamilton Rating Scale for Depression scale (HAMD-17) scores, and a negative correlation between the left precentral gyrus and the HAMD-17 scores in the female TRD group. This study will provide some clinical reference value for the sex differences in neuropathological mechanisms of TRD.

A comparative study of amplitude of low-frequence fluctuation of resting-state fMRI between the younger and older treatment-resistant depression in adults.

Background: Treatment-resistant depression (TRD) may have different physiopathological neuromechanism in different age groups. This study used the amplitude of low frequency fluctuations (ALFF) to initially compare abnormalities in local functional brain activity in younger and older patients with TRD. Materials and methods: A total of 21 older TRD patients, 19 younger TRD, 19 older healthy controls (HCs), and 19 younger HCs underwent resting-state functional MRI scans, and the images were analyzed using the ALFF and further analyzed for correlation between abnormal brain regions and clinical symptoms in TRD patients of different age groups. Results: Compared with the older TRD, the younger TRD group had increased ALFF in the left middle frontal gyrus and decreased ALFF in the left caudate nucleus. Compared with the matched HC group, ALFF was increased in the right middle temporal gyrus and left pallidum in the older TRD group, whereas no significant differences were found in the younger TRD group. In addition, ALFF values in the left middle frontal gyrus in the younger TRD group and in the right middle temporal gyrus in the older TRD were both positively correlated with the 17-item Hamilton Rating Scale for Depression score. Conclusion: Different neuropathological mechanisms may exist in TRD patients of different ages, especially in the left middle frontal gyrus and left caudate nucleus. This study is beneficial in providing potential key targets for the clinical management of TRD patients of different ages.

Altered functional connectivity in first-episode and recurrent depression: A resting-state functional magnetic resonance imaging study.

Background: Functional magnetic resonance imaging (fMRI) studies examining differences in the activity of brain networks between the first depressive episode (FDE) and recurrent depressive episode (RDE) are limited. The current study observed and compared the altered functional connectivity (FC) characteristics in the default mode network (DMN), cognitive control network (CCN), and affective network (AN) between the RDE and FDE. In addition, we further investigated the correlation between abnormal FC and clinical symptoms. Methods: We recruited 32 patients with the RDE, 31 patients with the FDE, and 30 healthy controls (HCs). All subjects underwent resting-state fMRI. The seed-based FC method was used to analyze the abnormal brain networks in the DMN, CCN, and AN among the three groups and further explore the correlation between abnormal FC and clinical symptoms. Results: One-way analysis of variance showed significant differences the FC in the DMN, CCN, and AN among the three groups in the frontal, parietal, temporal, and precuneus lobes and cerebellum. Compared with the RDE group, the FDE group generally showed reduced FC in the DMN, CCN, and AN. Compared with the HC group, the FDE group showed reduced FC in the DMN, CCN, and AN, while the RDE group showed reduced FC only in the DMN and AN. Moreover, the FC in the left posterior cingulate cortices and the right inferior temporal gyrus in the RDE group were positively correlated with the 17-item Hamilton Rating Scale for Depression (HAMD-17), and the FC in the left dorsolateral prefrontal cortices and the right precuneus in the FDE group were negatively correlated with the HAMD-17. Conclusions: The RDE and FDE groups showed multiple abnormal brain networks. However, the alterations of abnormal FC were more extensive and intensive in the FDE group.

Transcutaneous auricular vagus nerve immediate stimulation treatment for treatment-resistant depression: A functional magnetic resonance imaging study.

Objective: Transcutaneous auricular vagus nerve stimulation (taVNS) is effective for treatment-resistant depression (TRD). In the current study, we observed the immediate modulating brain effect of taVNS in patients with TRD using rest-state functional magnetic resonance imaging (rs-fMRI). Method: Forty patients with TRD and forty healthy controls (HCs) were recruited. Rs-fMRI was performed before and after 30 min of taVNS at baseline. The brain regions that presented significantly different the Regional Homogeneity (ReHo) between the TRD patients and HCs were selected as the ROI to calculate the functional connectivity (FC) of full brain. The correlations were estimated between the clinical scales' score and the functional brain changes. Results: Following taVNS stimulation treatment, TRD patients showed significantly reduced ReHo in the medial orbital frontal cortex (mOFC) (F = 18.06, P < 0.0001), ANCOVA of the mOFC-Based FC images revealed a significant interaction effect on the left inferior parietal gyrus (IPG) and left superior marginal gyrus (SMG) (F = 11.6615, P<0.001,F = 16.7520, P<0.0001). Among these regions, the HAMD and HAMA scores and ReHo/FC changes were not correlated. Conclusion: This study applied rs-fMRI technology to examine the effect of taVNS stimulation treatment on the brain activity of TRD. These results suggest that the brain response of TRD patients to taVNS treatment may be associated with the functional modulation of cortical regions including the medial orbital frontal cortex, the left inferior parietal gyrus, and the left superior marginal regions. Changes in these neuroimaging indices may represent the neural mechanisms underlying taVNS Immediate Stimulation treatment in TRD.

Acupuncture for poststroke hemiplegia focusing on cerebral bilateral connections: study protocol for a randomised controlled neuroimaging trial.

INTRODUCTION: Acupuncture is safe and effective for improving the motor function of poststroke hemiplegic patients, but there still exists a certain gap between clinical practice and understanding its neural mechanisms. The cerebral functional reconstruction after unilateral motor pathway injury exhibits a bilateral tendency, however current studies seldom pay attention to it. Hence, based on cerebral bilateral connections, the underlying mechanism of acupuncture in stroke rehabilitation remains an area for further research. The results of this study will increase our understanding of acupuncture-induced motor recovery in patients who had suffered a stroke and demonstrate the differences in brain response and clinical assessments. METHODS AND ANALYSIS: This is a single-centre, randomised controlled, paralleled neuroimaging trial, with patients and outcome assessors blinded. Thirty patients who had a stroke with motor dysfunction meeting the inclusion criteria will be randomly assigned (2:1) to receive either 10 sessions true or sham acupoints treatments (five sessions per week for 2 weeks). All the participants will receive conventional standard medical care and rehabilitation. Motor function assessments and neuroimaging scanning will be conducted before and after the entire acupuncture treatment. The clinical and neuroimaging data will be analysed, respectively. The voxel-mirrored homotopic connectivity will be the primary outcome and the primary effect indicator. The secondary outcomes comprise clinical evaluations and neuroimaging assessments, which include Fugl-Meyer Assessment, the National Institutes of Health Stroke Scale, fractional anisotropy and gray matter volume. The Needle Sensation Assessment Scale is an additional outcome. The correlation analysis will be explored between the neuroimaging indicators, clinical motor assessments and needle sensation. ETHICS AND DISSEMINATION: The protocol has been approved by the ethics committee of Dongzhimen Hospital affiliated to Beijing University of Chinese Medicine (DZMEC-KY-2018-04). The results of the neuroimaging trial will be disseminated through peer-reviewed publications and conferences. TRIAL REGISTRATION NUMBER: Chinese Clinical Trials Registry (ChiCTR 1800016263).