Hemodynamic alterations response to Chinese acupuncture therapy monitored by a custom near-infrared spectroscopy probe with an open hole.

Traditional acupuncture, a popular traditional Chinese medicine (TCM) technique, has demonstrated potential in relieving various ailments' symptoms. However, its black-box feedback loop model has limited proper evaluation and use by unskilled practitioners. This study aimed to analyze hemodynamic signals around acupoints during acupuncture to identify significant parameter changes. We designed hollow near-infrared spectroscopy (NIRS) probes for real-time measurements during acupuncture at acupoints, monitoring oxy-hemoglobin (HbO), deoxy-hemoglobin (Hb), and blood volume (HbT) changes. Acupuncture was performed on the "Xuehai" acupoint in 17 healthy subjects, with NIRS measuring hemodynamic alterations. Results showed significant and consistent increases in Hb and HbT around the acupoint, returning to baseline values after needle removal. One case of fainting revealed a significant Hb increase and HbO decrease. Acupuncture may induce tissue vasodilation and enhance oxygen consumption. This research provides a potential explanation for acupuncture's mechanism and emphasizes NIRS's potential in TCM.

Paraventricular Thalamus Dynamically Modulates Aversive Memory via Tuning Prefrontal Inhibitory Circuitry.

The impact of stress on the formation and expression of memory is well studied, especially on the contributions of stress hormones. But how stress affects brain circuitry dynamically to modulate memory is far less understood. Here, we used male C57BL6/J mice in an auditory fear conditioning as a model system to examine this question and focused on the impact of stress on dorsomedial prefrontal cortex (dmPFC) neurons which play an important role in probabilistic fear memory. We found that paraventricular thalamus (PVT) neurons are robustly activated by acute restraining stress. Elevated PVT activity during probabilistic fear memory expression increases spiking in the dmPFC somatostatin neurons which in turn suppresses spiking of dmPFC parvalbumin (PV) neurons, and reverts the usual low fear responses associated with probabilistic fear memory to high fear. This dynamic and reversible modulation allows the original memory to be preserved and modulated during memory expression. In contrast, elevated PVT activity during fear conditioning impairs synaptic modifications in the dmPFC PV-neurons and abolishes the formation of probabilistic fear memory. Thus, PVT functions as a stress sensor to modulate the formation and expression of aversive memory by tuning inhibitory functions in the prefrontal circuitry.SIGNIFICANCE STATEMENT The impact of stress on cognitive functions, such as memory and executive functions, are well documented especially on the impact by stress hormone. However, the contributions of brain circuitry are far less understood. Here, we show that a circuitry-based mechanism can dynamically modulate memory formation and expression, namely, higher stress-induced activity in paraventricular thalamus (PVT) impairs the formation and expression of probabilistic fear memory by elevating the activity of somatostatin-neurons to suppress spiking in dorsomedial prefrontal parvalbumin (PV) neurons. This stress impact on memory via dynamic tuning of prefrontal inhibition preserves the formed memory but enables a dynamic expression of memory. These findings have implications for better stress coping strategies as well as treatment options including better drug targets/mechanisms.

[Situation analysis of outcome indicators of randomized controlled trials of traditional Chinese medicine in treatment of hypertensive intracerebral hemorrhage in recent three years].

The study aims to analyze the outcome indicators of randomized controlled trial(RCT) of traditional Chinese medicine(TCM) in the treatment of hypertensive intracerebral hemorrhage(HICH) in recent three years, and thus provide suggestions for the future studies in this field. Four English databases, four Chinese databases and two online registration websites of clinical trials were searched. The RCTs published between January 2018 and September 2020 were screened. The risk of bias was assessed and outcome measures were classified. A total of 151 839 articles were retrieved, of which 44 RCTs were included for analysis after screening. The outcome measures of the included RCTs were classified into 7 categories, among which the symptoms/signs category showed the highest reporting rate. National Institute of Health stroke scale(72.73%) was the most frequently reported outcome indicator, while the vo-lume of intracerebral hemorrhage determined by computerized tomography(36.36%) was the most frequently reported lab test outcome. Most studies collect the outcomes at the end of treatment, while 9 studies reported long-term outcomes 3 months or more after onset. Compared with those of international clinical trials, the application of some of the outcomes was reasonable, focusing on patients' symptoms, quality of life and objective outcomes. However, there were still several problems: unclear primary and secondary outcome measures, insufficient attention to long-term prognosis, insufficient attention to social function, few TCM outcomes, lack of measurement blindness and the use of unreasonable composite outcomes. It is recommended that researchers should rationally design the outcome indicators of clinical trials and develop the core outcome set.

[Overview of systematic reviews/Meta-analysis of Xingnaojing Injection in treatment of intracerebral hemorrhage].

To overview of systematic reviews/Meta-analysis of Xingnaojing Injection(XNJ) in the treatment of intracerebral hemorrhage(ICH). The systematic reviews concerning XNJ in the treatment of ICH were retrieved from four Chinese databases, four English databases, Chinese Clinical Trial Registry and ClinicalTrail.gov, with the retrieval time set from their inception to September 2020. Following the independent screening and data extraction by two researchers, a measurement tool to assess systematic evaluation 2(AMSTAR 2) and grades of recommendation, assessment, development and evaluation(GRADE) system were used to evaluate the metho-dological, reporting and evidence qualities of the 10 included systematic reviews. The results showed that XNJ was superior to the wes-tern medicine or conventional treatment in improving the effective rate and National Institutes of Health stroke scale(NIHSS) score, Barthel index(BI), and Glasgow coma scale(GCS) score and Chinese stroke scale(CSS) score, and reducing the mortality and cerebral hematoma volume, without inducing obvious adverse reactions. In general, the methodological, reporting and evidence qualities of the 10 included systematic reviews were poor. The AMSTAR 2 scores showed that key items No. 2 and No. 16 failed to meet the stan-dard, resulting in poor methodological quality. There was only one outcome indicator graded by GRADE as intermediate quality, 43% indicators as low quality, 42% indicators as extremely low quality, and none as high quality. These available evidences have suggested that the methodological, reporting and evidence qualities of the systematic evaluation concerning XNJ for the treatment of ICH need to be improved. Most evidences support that XNJ was better than the western medicine or conventional treatment in the treatment of ICH, but the methodological quality and the reliability of outcome indicators in relevant systematic review were low. More high-quality studies are still required for further verification.

[Systematic review and Meta-analysis of efficacy and safety of acupuncture therapy on hypertensive intracerebral hemorrhage].

To systematically review the efficacy and safety of acupuncture combined with minimally invasive surgery or basic the-rapy in treating hypertensive intracerebral hemorrhage(HICH) patients compared with minimally invasive surgery or basic treatment. In this study, the four Chinese databases, the four English databases, Chinese Clinical Trial Registry and ClinicalTrail.gov, all above were systematically and comprehensively retrieved from the time of database establishment to September 10, 2020. Rando-mized controlled trials(RCTs) were screened out according to inclusion criteria and exclusion criteria established in advanced. The methodological quality of included studies was evaluated by the tool named "Cochrane bias risk assessment 6.1". Meta-analysis of the included studies was performed using RevMan 5.4, and the quality of outcome indicators was evaluated by the GRADE system. Finally, 17 studies were included, involving 1 852 patients with HICH, and the overall quality of the included studies was not high. According to Meta-analysis,(1)CSS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-3.50,95%CI[-4.39,-2.61],P<0.000 01);(2)NIHSS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-4.78,95%CI[-5.55,-4.00],P<0.000 01);(3)the cerebral hematoma volume of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-4.44,95%CI[-5.83,-3.04],P<0.000 01);(4)ADL score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=20.81,95%CI[17.25,24.37],P<0.000 01);(5)the GCS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=2.41,95%CI[1.90,2.91],P<0.000 01). The GRADE system showed an extremely low level of evidence for the above outcome indicators. Adverse reactions were mentioned only in two literatures, with no adverse reactions reported. The available evidence showed that acupuncture combined with minimally invasive surgery or basic therapy had a certain efficacy in patients of HICH compared with minimally invasive surgery or basic therapy. However, due to the high risk of bias in the included studies, its true efficacy needs to be verified by more high-quality studies in the future.

[Systematic review and Meta-analysis on efficacy and safety of Naoxueshu Oral Liquid in treatment of hypertensive intracerebral hemorrhage].

To systematically review the efficacy and safety of Naoxueshu Oral Liquid in treatment of hypertensive intracerebral hemorrhage, four Chinese databases, four English databases, clinical trials registration center(ClinicalTrials.gov) and Chinese clinical trial registry were retrieved. The retrieval time was from the establishment of each database to September 9, 2020. According to the set criteria, the randomized controlled trial(RCT) of Naoxueshu Oral Liquid combined with conventional Western medicine was selected. The "Cochrane bias risk assessment" tool was used to evaluate the quality of the included studies. RevMan 5.4.1 was used to conduct Meta-analysis of the included studies and GRADE system was used to evaluate the evidence quality of the outcome indicators. Eleven studies were finally included, with a total sample size of 1 221 cases, 612 cases in the treatment group and 609 cases in the control group. Meta-analysis showed that Naoxueshu Oral Liquid combined with conventional Western medicine had no significant difference compare with conventional Western medicine in reducing National Institute of health stroke scale(NIHSS) after 2 weeks of treatment for hypertensive intracerebral hemorrhage(MD=-1.59,95%CI[-3.46,0.29],P=0.10), but was superior to conventional Western medicine after 30 d of treatment(MD=-1.16,95%CI [-1.39,-0.94],P<0.000 01). Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine in improving Glasgow coma scale(MD=1.00,95%CI[0,2.00],P=0.05) and reducing the incidence of secondary brain insults(RR=0.38,95%CI[0.24,0.59],P<0.000 1), but there was no significant difference in increasing Barthel index(MD=1.00,95%CI[-0.30,2.30],P=0.13). In terms of effective rate, studies using Guideline for clinical trials of new patent Chinese medicines, NHISS or Glasgow outcome scale(GOS) had shown that Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine(RR_(Guideline for clinical trials of new patent Chinese medicines)=1.27,95%CI[1.10,1.46],P=0.001;RR_(NHISS)=1.26,95%CI[1.13,1.40],P<0.000 1;RR_(GOS)=1.54,95%CI[1.22,1.93],P=0.000 2). In reduction of hematoma volume, Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine after 2 and 4 weeks of treatment(MD_(2 week)=-2.31,95%CI[-3.12,-1.49],P<0.000 01;MD_(4 week)=-2.04,95%CI[-2.41,-1.68],P<0.000 01). GRADE system showed that the evidence level of the above outcome indicators was low and extremely low. In terms of adverse reactions, two of the included studies reported mild adverse reactions, and the rest of studies were not mentioned, so this study was not able to make a positive evaluation of the safety of Naoxueshu Oral Liquid. This study showed that compared with conventional Western medicine, combined Naoxueshu Oral Liquid may be better for hypertensive intracerebral hemorrhage. However, due to the high bias risk in the included studies, more large-sample and high-quality RCTs are still needed in the future.

Chinese herbal medicine for vascular cognitive impairment in cerebral small vessel disease: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Cerebral small vessel disease (CSVD) is the most common etiology of vascular cognitive impairment (VCI). VCI in CSVD (CSVD-VCI) shows a progressive course with multiple stages and is also associated with dysfunctions such as gait, emotional and behavioral, and urinary disturbances, which seriously affect the life quality of elderly people. In mainland China, Chinese herbal medicine (CHM) is clinically used for CSVD-VCI and presenting positive efficacy, but the evidence revealed in relevant clinical trials has not been systematically evaluated. The purpose of this study is to assess the current evidence available for the clinical efficacy and safety of CHM for CSVD-VCI. METHODS: A literature search of published RCTs up to April 30, 2020, has been conducted in the following 7 electronic databases: PubMed, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure Database (CNKI), Chinese Science and Technology Journals Database (VIP), Wanfang Database, and Chinese Biomedical Literature Service System (SinoMed). For unpublished studies, 2 clinical trial online registration websites will be searched: ClinicalTrials.gov and Chinese Clinical Trial Registry (ChiCTR). Only randomized controlled trials (RCTs) using CHM in the treatment of patients with CSVD-VCI, which compares CHM with no treatment, placebo, or other conventional treatments, will be included in this systematic review. Primary outcomes will be set as acknowledged scales measuring cognitive function. Secondary outcomes will involve activities of daily living, behavioral, and psychological symptoms, global performance of dementia, neurological function, biological markers of endothelial dysfunction, the clinical effective rate, and adverse events. After screening studies and extracting data, the Cochrane Collaborations tool for assessing risk of bias will be applied to assess the methodological quality of included RCTs. Review Manager Version 5.3 software will be used for data synthesis and statistical analysis. Subgroup analyses, sensitivity analyses, and meta-regression will be conducted to detect potential sources of heterogeneity. The funnel plot and Eggers test will be developed to evaluate publication bias, if available. We will perform the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to appraise the quality of evidence. RESULTS: Evidence exhibited in this systematic review will provide practical references in the field of CHM treating CSVD-VCI. Moreover, our detailed appraisals of methodological deficiencies of relevant RCTs will offer helpful advice for researchers who are designing trials of CHMs in the treatment of CSVD-VCI. CONCLUSION: The conclusion about the clinical efficacy and safety of CHM for CSVD-VCI will be provided for clinical plans, decisions, and policy developments in the full version of this systematic review. SYSTEMATIC REVIEW REGISTRATION: INPLASY202080120.

[Analysis of outcomes of randomized controlled trial on compound Chinese herbal medicine formulas in treatment of vascular cognitive impairment caused by cerebral small vessel].

The purpose of the study is to analyze the outcomes of randomized controlled trial(RCT) of Chinese herbal medicine formula(CHMF) in the treatment of vascular cognitive impairment caused by cerebral small vessel disease(CSVD-VCI), and provide suggestions for future studies in this field. Three English databases, four Chinese databases, and two online registration websites of clinical trials were searched with use of the search strategy established in advance. Relevant RCTs published in recent ten years were screened, and necessary information was extracted to assess the risk of bias and analyze the outcomes of these RCTs. As a result, a total of 10 461 articles were retrieved, of which 8 681 were kept after de-duplication, and 41 RCTs were included after screening, with a generally higher risk of bias. The outcomes of included RCTs were classified into 9 categories, namely, clinical symptom outcomes, neuroimaging outcomes, neuroelectrophysiological outcomes, blood biochemical outcomes, hemorheology outcomes, physical signs, syndrome scores of traditional Chinese medicine(TCM), clinical effective rate, and safety outcomes. Among them, the most frequently reported outcomes of included RCTs were blood biochemical outcomes, and clinical symptom outcomes showed the highest reporting rate. Besides, 9 RCTs reported syndrome scores of TCM as the outcomes and illustrated corresponding evaluation criteria. The analysis showed that the application of RCT outcomes in this field had clinical rationality and limitations, and there were also some deficiencies in the trial design level, namely, no distinction between primary and secondary outcomes, insufficient blind methods, not detailed description of outcomes, disunity of evaluation tools, and despised endpoint outcomes. These limitations and deficiencies were negatively affecting the quality of RCTs of CHMF in the treatment of CSVD-VCI. Therefore, we suggest that future researchers should be well prepared in the top-level design stage, and actively construct the core outcome set of this field, so as to improve the quality of clinical trials.

[Study on differentially expressed proteins of effect of kudiezi injection on cerebral cortexin rats with cerebral ischemic stroke and heat toxin syndrome].

This study is to investigate the modulation of Kudiezi (KDZ) injection on differential protein expression in cerebral cortex of rats with cerebral ischemic stroke and heat toxin syndrome established by intraperitoneal injection of carrageenan and middle cerebral artery occlusion (MCAO) methods. According to random number table rats were divided into three groups: drug group, model group and sham group. The tripheye tetrazolium chloride (TTC) staining and HE staining were used to observe brain tissue injury of rats. After therapeutic intervention with above drug for seventy-two hours, the level of differential protein expression was analyzed by two-dimensional gel electrophoresis (2-DE). The results show that there are differential protein expressions between cerebral ischemic stroke and heat toxin syndrome rats and sham rats. Furthermore, as a Chinese medicine injection with effect of clearing heat, resolving toxin and dredging collaterals, KDZ injection can decrease alleviate morphological changes of cerebral ischemia, regulate the levels of some differential proteins expression.

[Effect of harvest times on yield and quality of Isatidis Folium in Longzhong semi-arid region].

Different harvest times of Isatidis Folium had a significant effect on the yield and the quality of Isatidis Radix and Isatidis Folium. The harvest could increase the yield of Isatidis Folium, but reduce the yield of Isatidis Radix, the quality of Isatidis Radix and Isatidis Folium. One, two and three harvests of the Isatidis Folium reduced the yield of Isatidis Radix as 18.3%, 58.6%, 67.4% and increased the yield of the Folium as 107.3%, 86.3% and 116.6%. Ethanol-soluble extract of Isatidis Radix was 42.50%, 42.24%, 31.77%, which were 1.19%, 1.79%, 26.13% lower than those of the control, respectively. The water-soluble extract, indirubin, indigo content reduced with increase of the harvest times. Indirubin contents with two or three times harvests were higher than that of the control, but the content of water-soluble extract, ethanol-soluble extract, indigo were lower than those of the control.