Promoting the international acceptance of clinical studies about traditional Chinese medicine (TCM) interventions is a key strategy for internationalization of TCM. However, the complexities of TCM interventions—in terms of the theories, practice patterns, and components—pose challenges to the design and implementation of clinical studies that are well accepted by the international community. This article summarized the current status of clinical studies about TCM interventions that were published in international journals, explored underlying barriers hindering the international acceptance, and discussed potential strategies for future development.

Promoting the international acceptance of clinical studies about traditional Chinese medicine (TCM) interventions is a key strategy for internationalization of TCM. However, the complexities of TCM interventions—in terms of the theories, practice patterns, and components—pose challenges to the design and implementation of clinical studies that are well accepted by the international community. This article summarized the current status of clinical studies about TCM interventions that were published in international journals, explored underlying barriers hindering the international acceptance, and discussed potential strategies for future development.

Promoting the international acceptance of clinical studies about traditional Chinese medicine (TCM) interventions is a key strategy for internationalization of TCM. However, the complexities of TCM interventions—in terms of the theories, practice patterns, and components—pose challenges to the design and implementation of clinical studies that are well accepted by the international community. This article summarized the current status of clinical studies about TCM interventions that were published in international journals, explored underlying barriers hindering the international acceptance, and discussed potential strategies for future development.

Objective:To explore the effect of exercise on the memory of rats modeling vascular cognitive impairment (VCI) and also its effects on the hippocampal Sema3G/neuropilin-2 (Nrp2)/PlexinA4 signaling pathway.Methods:Eighteen male Sprague-Dawley rats were randomly divided into a sham-operated group, a model group, and an exercise group, each of 6. The model and exercise groups underwent VCI modeling via bilateral common carotid artery occlusion, while the sham-operated group received the same surgical procedure without vessel ligation or transection. Beginning forty-eight hours after the surgery, the exercise group carried out daily 30-minute treadmill training sessions, 5 days a week, for a total of 4 weeks, while the other two groups were placed on the same treadmill with it not in operation. After the intervention, cognitive functioning was assessed using the novel object recognition (NOR) test and a Y-maze test. Western blotting was employed to evaluate the expression of Sema3G, Nrp2, PlexinA4, and Rac1 in the hippocampus. Immunofluorescence staining was used to observe the distribution of Nrp2 and PlexinA4 in the hippocampus.Results:Compared with the model group, the exercise group exhibited significantly higher NOR indices during both the short-term and long-term memory testing phases after the intervention. Those rats also tended to have significantly longer total exploration times in the novel arm of the Y-maze test. The western blotting revealed that the expression levels of Sema3G, PlexinA4, and Rac1 in the hippocampus were significantly higher in the exercise group compared to the model group, on average. Immunofluorescence showed significantly increased PlexinA4 fluorescence intensity in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus, and significantly elevated Nrp2 fluorescence intensity in the CA3 region in the exercise group compared to the model group. The Pearson correlation coefficients for Nrp2/PlexinA4 co-localization in the CA1, CA3 and DG regions were significantly higher in the exercise group than in the model group.Conclusions:Exercise training significantly improves memory function in rats with VCI, and this effect may be associated with activation of the hippocampal Sema3G/Nrp2/PlexinA4 signaling pathway.

Objective:Drug safety assessments based on real-world data are often challenged by both treatment switching and rare events. In this study, we used statistical simulations to investigate the effects of switching rates and treatment effects on the statistical performance of commonly used analytical strategies and methods under overlapping scenarios of treatment switching and rare events.Methods:The simulation scenario was set up as a bidirectional treatment switching (allowing the control group to switch to the treatment group and the treatment group to switch to the control group), and the event rates were set at approximately 2%, 5%, and 20%. Different simulation scenarios were generated with sufficient sample size to consider switching rate and relative treatment effect. The simulated datasets were analyzed using three types of analysis strategy, i.e. intention to treat (ITT), per protocol (PP), and as treated (AT). The performance of five indicators, namely percentage bias, mean square error, empirical standard error, coverage, and rejection rate, were compared among the different methods in different scenarios, and recommendations for method selection were given.Results:In terms of analytical strategies and methods, AT analysis were relatively optimal in terms of percentage bias and accuracy, followed by PP analysis and ITT analysis. When the relative treatment effects converged (e.g. HR=1.0), both the ITT analysis and the time-dependent AT approaches (marginal structural model, time-dependent Cox regression model or time-dependent propensity score matching) performed well; when the relative treatment effects were small (e.g. HR=0.8), the marginal structural model was the most optimal; when the relative treatment effects were large (e.g. HR=0.6 or 0.4), the approaches of using a censored treatment for switchers in the AT analysis were more accurate. In addition, the time-dependent AT approaches had the highest rejection rate when there was a difference in treatment effect between the two groups, and the ITT analysis had the lowest rejection rate. Conclusions:For the dual challenges of bidirectional switching and rare events in real-world drug safety evaluations, adequate sample size is a prerequisite for accurate estimation of treatment effects, while switching rates and effect sizes of switched drugs might also affect estimation accuracy. Appropriate strategies and methods should be selected for the analysis. It is necessary to consider whether the event is rare or not, the switching rate and the expected treatment effect size of the two types of treatment to select appropriate analysis strategies and methods.

Objective:Drug safety assessments based on real-world data are often challenged by both treatment switching and rare events. In this study, we used statistical simulations to investigate the effects of switching rates and treatment effects on the statistical performance of commonly used analytical strategies and methods under overlapping scenarios of treatment switching and rare events.Methods:The simulation scenario was set up as a bidirectional treatment switching (allowing the control group to switch to the treatment group and the treatment group to switch to the control group), and the event rates were set at approximately 2%, 5%, and 20%. Different simulation scenarios were generated with sufficient sample size to consider switching rate and relative treatment effect. The simulated datasets were analyzed using three types of analysis strategy, i.e. intention to treat (ITT), per protocol (PP), and as treated (AT). The performance of five indicators, namely percentage bias, mean square error, empirical standard error, coverage, and rejection rate, were compared among the different methods in different scenarios, and recommendations for method selection were given.Results:In terms of analytical strategies and methods, AT analysis were relatively optimal in terms of percentage bias and accuracy, followed by PP analysis and ITT analysis. When the relative treatment effects converged (e.g. HR=1.0), both the ITT analysis and the time-dependent AT approaches (marginal structural model, time-dependent Cox regression model or time-dependent propensity score matching) performed well; when the relative treatment effects were small (e.g. HR=0.8), the marginal structural model was the most optimal; when the relative treatment effects were large (e.g. HR=0.6 or 0.4), the approaches of using a censored treatment for switchers in the AT analysis were more accurate. In addition, the time-dependent AT approaches had the highest rejection rate when there was a difference in treatment effect between the two groups, and the ITT analysis had the lowest rejection rate. Conclusions:For the dual challenges of bidirectional switching and rare events in real-world drug safety evaluations, adequate sample size is a prerequisite for accurate estimation of treatment effects, while switching rates and effect sizes of switched drugs might also affect estimation accuracy. Appropriate strategies and methods should be selected for the analysis. It is necessary to consider whether the event is rare or not, the switching rate and the expected treatment effect size of the two types of treatment to select appropriate analysis strategies and methods.

Objective:To explore the effect of exercise on the memory of rats modeling vascular cognitive impairment (VCI) and also its effects on the hippocampal Sema3G/neuropilin-2 (Nrp2)/PlexinA4 signaling pathway.Methods:Eighteen male Sprague-Dawley rats were randomly divided into a sham-operated group, a model group, and an exercise group, each of 6. The model and exercise groups underwent VCI modeling via bilateral common carotid artery occlusion, while the sham-operated group received the same surgical procedure without vessel ligation or transection. Beginning forty-eight hours after the surgery, the exercise group carried out daily 30-minute treadmill training sessions, 5 days a week, for a total of 4 weeks, while the other two groups were placed on the same treadmill with it not in operation. After the intervention, cognitive functioning was assessed using the novel object recognition (NOR) test and a Y-maze test. Western blotting was employed to evaluate the expression of Sema3G, Nrp2, PlexinA4, and Rac1 in the hippocampus. Immunofluorescence staining was used to observe the distribution of Nrp2 and PlexinA4 in the hippocampus.Results:Compared with the model group, the exercise group exhibited significantly higher NOR indices during both the short-term and long-term memory testing phases after the intervention. Those rats also tended to have significantly longer total exploration times in the novel arm of the Y-maze test. The western blotting revealed that the expression levels of Sema3G, PlexinA4, and Rac1 in the hippocampus were significantly higher in the exercise group compared to the model group, on average. Immunofluorescence showed significantly increased PlexinA4 fluorescence intensity in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus, and significantly elevated Nrp2 fluorescence intensity in the CA3 region in the exercise group compared to the model group. The Pearson correlation coefficients for Nrp2/PlexinA4 co-localization in the CA1, CA3 and DG regions were significantly higher in the exercise group than in the model group.Conclusions:Exercise training significantly improves memory function in rats with VCI, and this effect may be associated with activation of the hippocampal Sema3G/Nrp2/PlexinA4 signaling pathway.

The prefrontal cortex and hippocampus may support sequential working memory beyond episodic memory and spatial navigation. This stereoelectroencephalography (SEEG) study investigated how the dorsolateral prefrontal cortex (DLPFC) interacts with the hippocampus in the online processing of sequential information. Twenty patients with epilepsy (eight women, age 27.6 ± 8.2 years) completed a line ordering task with SEEG recordings over the DLPFC and the hippocampus. Participants showed longer thinking times and more recall errors when asked to arrange random lines clockwise (random trials) than to maintain ordered lines (ordered trials) before recalling the orientation of a particular line. First, the ordering-related increase in thinking time and recall error was associated with a transient theta power increase in the hippocampus and a sustained theta power increase in the DLPFC (3-10 Hz). In particular, the hippocampal theta power increase correlated with the memory precision of line orientation. Second, theta phase coherences between the DLPFC and hippocampus were enhanced for ordering, especially for more precisely memorized lines. Third, the theta band DLPFC → hippocampus influence was selectively enhanced for ordering, especially for more precisely memorized lines. This study suggests that theta oscillations may support DLPFC-hippocampal interactions in the online processing of sequential information.
Adult ; Female ; Humans ; Young Adult ; Epilepsy ; Hippocampus ; Memory, Short-Term ; Mental Recall ; Prefrontal Cortex ; Theta Rhythm ; Male

Objective To explore the mediating effect of fatigue between social support and depression in hospitalized patients with ischemic stroke,so as to provide reference for improving post-stroke depression.Methods A total of 142 hospitalized patients with ischemic stroke were enrolled and investigation was conducted with self-rating depression scale(SDS),social support rating scale(SSRS),and fatigue severity scale(FSS).Spearman's correlation analysis was used to analyze the correlation between the variables.A model for the mediating effect between the variables was established by using the AMOS 23.0 software to analyze the mediating effect of fatigue between social support and depression.The Bootstrap method was used to test the significance of intermediary effect.Results The scores for SDS,SSRS,and FSS in the hospitalized ischemic stroke patients enrolled were 48.96±9.09,31.34±8.35,and 30.70±13.99,respectively.Spearman's correlation analysis showed that depression was positively correlated with fatigue and negatively correlated with social support.In addition,fatigue was negatively correlated with social support.Analysis of the mediating effect model established that fatigue played a mediating role between social support and depression in patients with ischemic stroke,with the mediating effect value being-0.170 and the mediating effect accounting for 90.0％of the total effect.Conclusion The effect of social support on depression in hospitalized patients with ischemic stroke is mainly achieved by affecting the sense of fatigue.Health workers should pay attention to the severity of fatigue of patients and reduce their sense of fatigue as much as possible,which will help enhance social support for the patients and reduce their depression.

Object:To explore the clinical effect of periacetabular osteotomy (PAO) in the treatment of developmental dysplasia of hip (DDH).Methods:The clinical data of 305 patients with DDH admitted to Tangshan Second Hospital from January 2012 to June 2018 were analyzed retrospectively. All patients were treated with PAO alone. There were 123 cases of left hip dysplasia, 131 cases of right hip dysplasia and 51 cases of double hip dysplasia (356 hips in total). The patients underwent X-ray examination before and on the second day after operation to compare the acetabular index and the lateral center edge angle (LCEA) and the anterior center edge angle (ACEA) of the acetabulum before and after operation. The ability of daily living and hip joint function were evaluated before and 6 months after operation, and Barthel index and Harris score of hip joint were compared before and after treatment. The measurement data with normal distribution are expressed in xˉ± s, and the paired t test was used for comparison before and after operation. The measurement data of non-normal distribution is expressed by M( Q1, Q3), and the comparison before and after surgery is performed by the rank sum test. Results:On the second day after operation, the LCEA and ACEA of 356 hip joints in 305 patients were greater than those before operation (32.5(20.0,47.5)° vs 8.5(-18.5 23.0)°, 29.0(18.5,52.3)° vs 2.5(-20.8, 24.5)°), while the acetabulum index was lower than that before operation (6.7(-8.4,12.5)° vs 26.8(10.0, 62.3)°), and the differences were statistically significant ( Z values were 51.50, 45.37, 32.22, all P<0.001). After 6 months of follow-up, the Barthel score and Harris score of the hip joint were higher than those before the operation (92.5±1.3) scores vs (65.6±1.5) scores, (96.4±2.5) scores vs (85.1±1.3) scores, and the difference was statistically significant ( t values were 335.56 and 89.70, both P<0.001). Conclusions:PAO can make the acetabulum cover the femoral head well through acetabular transposition, improve the ability of daily living and hip joint function of DDH patients, reduce pain, increase joint range of motion, and correct limb deformities. It is an effective means to treat DDH.