Extending the Grading of Recommendations Assessment, Development and Evaluation (GRADE) in Traditional Chinese Medicine (TCM): The GRADE-TCM.

AIM: To extend and form the "Grading of Recommendations Assessment, Development and Evaluation in Traditional Chinese Medicine" (GRADE-TCM). METHODS: Methodologies were systematically reviewed and analyzed concerning evidence-based TCM guidelines worldwide. A survey questionnaire was developed based on the literature review and open-end expert interviews. Then, we performed expert consensus, discussion meeting, opinion collection, external examination, and the GRADE-TCM was formed eventually. RESULTS: 265 Chinese and English TCM guidelines were included and analyzed. Five experts completed the open-end interviews. Ten methodological entries were summarized, screened and selected. One round of consensus was conducted, including a total of 22 experts and 220 valid questionnaire entries, concerning 1) selection of the GRADE, 2) GRADE-TCM upgrading criteria, 3) GRADE-TCM evaluation standard, 4) principles of consensus and recommendation, and 5) presentation of the GRADE-TCM and recommendation. Finally, consensus was reached on the above 10 entries, and the results were of high importance (with voting percentages ranging from 50 % to 81.82 % for "very important" rating) and strong reliability (with the Cr ranging from 0.93 to 0.99). Expert discussion meeting (with 40 experts), opinion collection (in two online platforms) and external examination (with 14 third-party experts) were conducted, and the GRADE-TCM was established eventually. CONCLUSION: GRADE-TCM provides a new extended evidence-based evaluation standard for TCM guidelines. In GRADE-TCM, international evidence-based norms, characteristics of TCM intervention, and inheritance of TCM culture were combined organically and followed. This is helpful for localization of the GRADE in TCM and internationalization of TCM guidelines.

Efficacy of acupuncture as an adjunctive treatment to patients with stable COPD: a multicenter, randomized, sham-controlled trial protocol.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease and the third leading cause of death worldwide. Previous evidence has shown that acupuncture may be an effective complementary alternative therapy for stable COPD. However, large-sample, rigorously designed long-term follow-up studies still need to be completed. Notably, the relationship between the frequency of acupuncture and clinical efficacy in studies on acupuncture for stable COPD still needs further validation. This study aims to evaluate the efficacy and safety of acupuncture for stable COPD and further investigate the dose-effect relationship of acupuncture. METHODS/DESIGN: This is a multicenter, randomized, controlled trial that uses central randomization to randomly allocate 550 participants in a 1:1:1:1:1 ratio to once a week acupuncture group, twice a week acupuncture group, three times a week acupuncture group, sham acupuncture group and waiting-list control group. The sham acupuncture group will receive placebo acupuncture treatments three times per week, and the waiting-list control group will not receive any form of acupuncture intervention. The study consists of a 2-week baseline, 12-week of treatment, and 52-week of follow-up. Patients with COPD between 40 to 80 years old who have received stable Western medication within the previous 3 months and have had at least 1 moderate or severe acute exacerbation within the past 1 year will be included in the study. Basic treatment will remain the same for all participants. The primary outcome is the proportion of responders at week 12. Secondary outcomes include the proportion of responders at week 64, change in the St. George's Respiratory Questionnaire (SGRQ) Scale, change in the Modified-Medical Research Council (mMRC) Scale, change in the COPD Assessment Test (CAT) Scale, change in the Lung Function Screening Indicators (LFSI), change in the 6-min walk distance (6-MWD), change in Short-Form 36 Health Survey (SF-36) Scale, the number of moderate and severe acute exacerbations and adverse event rate during the follow-up period. DISCUSSION: This study will provide robust evidence on whether acupuncture is safe and effective for treating stable COPD. Meanwhile, comparing the differences in efficacy between different acupuncture frequencies will further promote the optimization of acupuncture for stable COPD. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2200058757), on April 16, 2022.

Association of vitamins B1 and B2 intake with early-onset sarcopenia in the general adult population of the US: a cross-sectional study of NHANES data from 2011 to 2018.

Background: Early-onset sarcopenia refers to the progressive loss of muscle mass and function that occurs at an early age. This condition perpetuates the vicious cycle of muscle loss and is associated with adverse outcomes. It is important to identify the contributing factors for early intervention and prevention. While diet is known to impact muscle mass, the association of B vitamins with early-onset sarcopenia remains unexplored. Objectives: To investigate the association of B vitamins intake with early-onset sarcopenia risk in a cross-sectional study. Methods: We conducted data analysis on a total of 8,711 participants aged between 20 and 59 years who took part in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Early-onset sarcopenia was defined as a SMI measured by DXA that was one standard deviation below the sex-specific mean of the reference population. B vitamins intake (B1, B2, B3, B6, B9, and B12) was assessed by 24-h dietary recall. We used weighted multiple logistic regression and RCS models to estimate the OR and 95% CI of sarcopenia by B vitamins intake, adjusting for demographic, physical, lifestyle, comorbidities, and nutritional covariates. Results: Higher intake of vitamin B1 was associated with a 22% lower sarcopenia risk (OR = 0.78, CI = 0.63-0.97, p = 0.022), and higher intake of vitamin B2 with a 16% lower risk (OR = 0.84, CI = 0.74-0.97, p = 0.012) in both genders. Gender-specific analyses showed a 28% reduction in sarcopenia risk among males with each additional mg of vitamin B1 intake (OR = 0.72, CI = 0.52-0.97, p = 0.038), and a 26% decrease among females with each additional mg of vitamin B2 intake (OR = 0.74, CI = 0.57-0.96, p = 0.021). No significant differences were found between vitamin B2 and males, or between vitamin B1 and females. The RCS model suggested a nonlinear relationship between vitamin B2 intake and sarcopenia risk (POverall = 0.001, PNonlinear = 0.033), with a plateau effect above 3 mg/d. Conclusion: Higher intake of vitamin B1 and B2 may lower the risk of early-onset sarcopenia, with gender differences. This suggests the potential of nutritional intervention by increasing these vitamins intake through diet and supplements. Further research is warranted to elucidate the mechanisms and design targeted interventions.

Rational design of NIR-II molecule-engineered nanoplatform for preoperative downstaging and imaging-guided surgery of orthotopic hepatic tumor.

Orthotopic advanced hepatic tumor resection without precise location and preoperative downstaging may cause clinical postoperative recurrence and metastasis. Early accurate monitoring and tumor size reduction based on the multifunctional diagnostic-therapeutic integration platform could improve real-time imaging-guided resection efficacy. Here, a Near-Infrared II/Photoacoustic Imaging/Magnetic Resonance Imaging (NIR-II/PAI/MRI) organic nanoplatform IRFEP-FA-DOTA-Gd (IFDG) is developed for integrated diagnosis and treatment of orthotopic hepatic tumor. The IFDG is designed rationally based on the core "S-D-A-D-S" NIR-II probe IRFEP modified with folic acid (FA) for active tumor targeting and Gd-DOTA agent for MR imaging. The IFDG exhibits several advantages, including efficient tumor tissue accumulation, good tumor margin imaging effect, and excellent photothermal conversion effect. Therefore, the IFDG could realize accurate long-term monitoring and photothermal therapy non-invasively of the hepatic tumor to reduce its size. Next, the complete resection of the hepatic tumor in situ lesions could be realized by the intraoperative real-time NIR-II imaging guidance. Notably, the preoperative downstaging strategy is confirmed to lower the postoperative recurrence rate of the liver cancer patients under middle and advanced stage effectively with fewer side effects. Overall, the designed nanoplatform demonstrates great potential as a diagnostic-therapeutic integration platform for precise imaging-guided surgical navigation of orthotopic hepatic tumors with a low recurrence rate after surgery, providing a paradigm for diagnosing and treating the advanced tumors in the future clinical translation application.

Acupuncture as adjunctive therapy for patients with AECOPD: study protocol for a multicenter, randomized controlled trial.

Background: The acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common respiratory disease among older adults, which imposes a significant burden on individuals and society and poses a major challenge to the global public health system due to its high morbidity and mortality. Acupuncture is effective for AECOPD, but its efficacy has been questioned due to the limited methodological quality. Thus, we aim to investigate the efficacy of acupuncture as adjunctive therapy for AECOPD and determine whether the efficacy of acupuncture differs with the type of acupoint combinations. Methods and analysis: This study proposes a prospective, multicenter randomized controlled trial that will comprise four groups, including two acupuncture treatment groups, one sham acupuncture group, and one basic treatment group. The acupuncture treatment groups will be distinguished by their focus on different patterns of acupoint combination, namely the Xi-cleft and He-sea acupoint combination and the Eight Confluence points acupoint combination, which may vary in clinical efficacy based on traditional acupuncture theories. The study aims to randomize 556 patients in a 1:1:1:1 ratio across the four groups. Each patient in acupuncture group or sham acupuncture group will receive routine drug therapy and 7 sessions of acupuncture treatment over 1 week. Participants in the basic treatment group will only receive routine drug therapy. The trial will be conducted in seven hospitals located in China. The primary outcomes in this trial will include differences in the Breathlessness, Cough, and Sputum Scale (BCSS) before randomization, 7 days after randomization, 5 and 9 weeks after randomization. Ethics and dissemination: Ethical approval was obtained from the Sichuan Regional Ethics Review of Committee on Traditional Chinese Medicine (Approval ID: 2022KL-068). The results of this study will be distributed through peer-reviewed journals.Clinical Trial Registration: ClinicalTrials.gov, identifier ChiCTR2200064484.

Research trends of acupuncture therapy on postoperative nausea and vomiting from 2011 to 2023: A bibliometric analysis.

BACKGROUND: The utilization of acupuncture as a therapeutic intervention for the management of postoperative nausea and vomiting has experienced a notable increase in its popularity, and the purpose of this analysis is to provide a comprehensive understanding of the level of concern within the academic discipline and the main contributors and their partnership, as well as to identify research focal points and trends. METHODS: A comprehensive search was carried out to identify relevant articles on the topic of acupuncture therapy for PONV in the Web of Science and China National Knowledge Internet. The search spanned from January 1, 2011, to June 6, 2023. The annual publications were count to see the degree of scholarly attention devoted to the discipline and how it has changed over time. A statistical analysis of article distribution across various journals was conducted to serve a rough indicator for assessing the quality of articles. And a bibliometric analysis was conducted using the software CiteSpace to visually analyze various aspects of the literature. Analyze authors, institutions and countries to identify the main contributors and their collaborative relationship; and analyze keywords and references to explore research hotspots and trends. RESULTS: This study examined a comprehensive collection of 819 articles focused on acupuncture therapy for PONV, demonstrating a varying upward trend in the quantity of publications. Notably, the most productive author and institution were identified as Zheng Man and Guangzhou University of Traditional Chinese Medicine, respectively. While China had the highest number of publications, the United States held a greater prominence in this specific field. Collaboration among contributors was found to be weak. High-frequency keywords in the publications included "transcutaneous electrical acupoint stimulation," "electroacupuncture," "pain," and so forth. The literature with the highest citation count pertained to "Stimulation of the wrist acupuncture point PC6 for preventing postoperative nausea and vomiting," while the article with the highest centrality was "Consensus Guidelines for the Management of Postoperative Nausea and Vomiting." Several large clusters obtained from the references are also included "postoperative pain," "transcutaneous electrical acupoint stimulation". Nothing pertaining to mechanism study was found in the analysis results. CONCLUSION: The utilization of acupuncture for the treatment of postoperative nausea and vomiting has been gaining increasing recognition, although there remains room for improvement in the quality of research conducted in this area. Chinese authors and institutions have emerged as significant contributors to this field, while the United States has demonstrated greater proficiency in fostering collaborative efforts. It is imperative to enhance collaboration among these contributors. The current focal points of acupuncture for PONV encompass pain management, electroacupuncture, auricular acupuncture, and transcutaneous electrical acupoint stimulation. Additionally, TEA and enhanced recovery after surgery have been identified as the forefronts of research in this particular domain. In addition, there is still much room for research in the aspect of mechanism and insurance coverage. This study provides an in-depth perspective on acupuncture for PONV, which offers reference material for clinicians with rational choice of therapeutic scheme, educators with hot topics, and researchers with valuable research directions.

First Report of Leaf Spot Caused by Alternaria alternata on Cyclocodon lancifolius in China.

Cyclocodon lancifolius Bunge in the family Campanulaceae, and commonly known as Hong Guo Ginseng, is found in the Indonesia, Philippines, Vietnam, Japan, and China. The leaves and roots of C. lancifolius are widely used as tonics by ethnic minorities in Guizhou and Hunan Provinces in China. In addition, the fruit is edible, and it is a new resource for both medicine and food. In June 2022, symptoms of leaf spot (Fig 1 A and B.) were observed on C. lancifolius plants in the medicinal plant greenhouse of Guizhou University of Traditional Chinese Medicine (106°61'E, 26°39'N), Guizhou Province. The incidence of leaf spot on C. lancifolius was approximately 40 to 70% of all leaves in canopy. Early symptoms on leaves were small circular or irregular brown spots. As the disease progressed the lesions gradually expanded, and multiple lesions coalesced to form large irregular brown spots. Eventually the seedlings died and leaves of mature plants wilted. In order to isolate the pathogen, ten leaf pieces (5×5 mm) were cut from the junction of the diseased and the healthy tissues, surface sterilized with 75% ethanol for 30 s, 0.1% mercuric chloride (HgCl2) solution for 60 s, rinsed in sterile water three times, finally dried and placed on potato dextrose agar (PDA) and cultured in the dark at 27°C for 4 days. Five purified fungal isolates were obtained by single spore isolation. The colonies were olivaceous to dark olive with white margins and abundant aerial mycelia. On potato carrot agar (PCA) medium, these fungi produced septate conidiophores. Conidia were obclavate or ellipsoid, brown, with one to four transverse septa and one to two longitudinal septa. Spores measured 7.64 to 14.20 × 3.32 to 6.38 µm (n=50). These morphological characteristics are consistent with Alternaria alternata (S. P. Wiltshire. 1933). To further confirm the identification, four genomic DNA regions including the ribosomal DNA internal transcribed spacer (ITS), translation elongation factor 1-a gene (TEF), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), RNA polymerase II second largest subunit (RPB2), and Alternaria major allergen gene (Alt a1) were amplified and sequenced with primers ITS1/ITS4 (White et al. 1990), TEF1-728F/TEF1-986R (Carbone and Kohn 1999), gpd1/gpd2 (Berbee et al. 1999), RPB2-5F/RPB2-7cR (Liu et al. 1999), and Alt-for/Alt-rev (Hong et al. 2005), respectively. Sequences were deposited in GenBank with accession Nos. ITS: OQ128111, OQ690707, and OQ690708; TEF: OQ200380, OQ700996, and OQ700998; GAPDH: OQ200378, OQ700993, and OQ700995; RPB2:OQ200379, OQ701002, and OQ701004; Alt: OQ675614, OQ700999, and OQ701001. In a BLAST search, the sequences were 99-100% identical with corresponding sequences of A. alternata. A maximum likelihood phylogenetic tree was constructed with the combined sequence data sets of ITS, TEF, GAPDH, RPB2, and Alt a1 using MEGA 11. The isolate DHY0, DHY1, and DHY3 clustered with A. alternata (J. H. C. Woudenberg et al. 2015) (Fig. 2). To fulfill Koch's postulates, leaves on three healthy 3-month-old potted C. lancifolius seedlings were wounded with sterile needles and inoculated with 5 mm diameter mycelium, which was covered moist by sterile cotton for 24 h. Sterile water was used as the control. After inoculation, the plants were incubated at 27°C, 85% relative humidity, and a 12 h photoperiod. The experiment was repeated three times. Fifteen days after inoculation, all the leaves showed leaf spot symptoms that were similar to those observed in the greenhouse, while control leaves were asymptomatic (Fig. 1). A. alternata was successfully re-isolated from the symptomatic leaves and identified by morphology and the molecular methods described above. This pathogen has been reported to cause a leaf disease in a wide range of vegetables (Zhang et al. 2021), flowers (Zhang et al. 2022), and medicinal plants (Xing et al. 2020). To the best of our knowledge, this is the first report of A. alternata causing leaf spot on C. lancifolius in China. The accurate identification of this pathogen will provide a basis for the prevention and control of C. lancifolius leaf spot disease in the future.

NIR-II Imaging-Guided Mitochondrial-Targeting Organic Nanoparticles for Multimodal Synergistic Tumor Therapy.

Effectively interfering energy metabolism in tumor cells and simultaneously activating the in vivo immune system to perform immune attacks are meaningful for tumor treatment. However, precisely targeted therapy is still a huge challenge. Herein, a mitochondrial-targeting phototheranostic system, FE-T nanoparticles (FE-T NPs) are developed to damage mitochondria in tumor cells and change the tumor immunosuppressive microenvironment. FE-T NPs are engineered by encapsulating the near-infrared (NIR) absorbed photosensitizer IR-FE-TPP within amphiphilic copolymer DSPE-SS-PEG-COOH for high-performing with simultaneous mitochondrial-targeting, near-infrared II (NIR-II) fluorescence imaging, and synchronous photothermal therapy (PTT) /photodynamic therapy (PDT) /immune therapy (IMT). In tumor treatment, the disulfide in the copolymer can be cleaved by excess intracellular glutathione (GSH) to release IR-FE-TPP and accumulate in mitochondria. After 808 nm irradiation, the mitochondrial localization of FE-T NPs generated reactive oxygen species (ROS), and hyperthermia, leading to mitochondrial dysfunction, photoinductive apoptosis, and immunogenic cell death (ICD). Notably, in situ enhanced PDT/PTT in vivo via mitochondrial-targeting with FE-T NPs boosts highly efficient ICD toward excellent antitumor immune response. FE-T NPs provide an effective mitochondrial-targeting phototheranostic nanoplatform for imaging-guided tumor therapy.

Role of GRPR in Acupuncture Intervention in the "Itch-scratch Vicious Cycle" Spinal Circuit of Chronic Pruritus.

Many previous studies have shown the potential antipruritic effect of acupuncture. This paper reviews the antipruritic mechanisms of acupuncture according to these aspects: sample characteristics, detail of intervention, and effects evaluation. The majority of research on acupuncture's antipruritic effect has focused on primary afferents of the peripheral mechanism. Relatively few studies, however, have addressed the central mechanisms. Combination the latest research achievements of chronic itch, gastrin-releasing peptide receptor (GRPR) in the dorsal horn of the spinal cord may represent the first molecule identified that is dedicated to mediating the itch response and may provide an important therapeutic target for the treatment of chronic pruritic conditions. Therefore, GRPR may be a new target for acupuncture to relieve itch in the future and provide new ideas for acupuncture intervention in the mechanisms of the spinal level of the "itch-scratch vicious cycle" of chronic itch.

The formation of starch-lipid complexes in instant rice noodles incorporated with different fatty acids: Effect on the structure, in vitro enzymatic digestibility and retrogradation properties during storage.

The formation of starch-lipid complexes in instant rice noodles (IRN) free from and incorporated with fatty acids (FAs) and their impacts on textural, in vitro digestive and retrogradation properties were investigated. The gelatinization enthalpy values of IRN samples (1.24-4.93 J/g) were noticeably decreased (P < 0.05) compared to rice starch samples (2.54-6.89 J/g) fortified with FAs. Additionally, long-chain saturated FAs (stearic acid (SA, C18:0)) complexes produced higher ordered structures than the shorter-chain FAs (C12:0-C16:0), for 18-carbon FAs, the unsaturated FAs (linoleic acid (LOA, C18:2)) exhibited the strongest intermolecular interactions with rice starch. The relative crystallinity of IRN (27.01%-38.47%) was lower than the rice starch-FAs complexes (38.36%-56.80%). FAs delayed the retrogradation degree of IRN storaged at 4 °C for 21 days ascribed to the formation of V-type complexes. Higher enzymatic resistance was observed in IRN added FAs with resistant starch content increased from 5.13% to 14.42% (LOA), and the sample fortified with SA exhibited the highest slowly digestible starch content (35.92%). SEM revealed that the IRN compounded with palmitic acid, SA and LOA displayed more compact and regular structures. Overall, the formation of starch-FAs complexes probably is a novel strategy in improving the textural, digestive, and retrogradation properties of IRN.

A mitochondria-targeted molecular phototheranostic platform for NIR-II imaging-guided synergistic photothermal/photodynamic/immune therapy.

Phototherapy is a conducive and non-invasive strategy for cancer therapy under light irradiation. Inspiringly, fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) holds a great promise for imaging-guided phototherapy with deep penetration and high spatiotemporal resolution. However, most phototherapeutics still face great challenges, including complicated synthesis of agents, potential biotoxicity and unsatisfied therapeutic outcomes. Herein, a near-infrared laser triggered molecular photosensitizer FEPT, modified with triphenylphosphine PEGylation (PEG2000-TPP), is developed for NIR-II imaging-guided mitochondria-targeting synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/immune therapy (IMT). The mitochondria-targeting photosensitizer FEPT can produce reactive oxygen species (ROS) and hyperpyrexia upon 808 nm laser irradiation, resulting in mitochondrial dysfunction and photo-induced apoptosis via caspase-3 pathway. Phototherapy-induced hyperthermia or ROS triggers the release of immunogenic intracellular substrates from dying tumor cells, thereby promoting the activation of antitumor immunity. Herein, this work provides a practicable strategy to develop a molecular phototheranostic platform for imaging-guided cancer therapy via mitochondria-targeting.

Ameliorating effects of electroacupuncture on the low-grade intestinal inflammation in rat model of diarrhea-predominant irritable bowel syndrome.

BACKGROUND AND AIM: We aim to investigate the effects and mechanisms of electroacupuncture (EA) at ST25 and ST37 on the intestinal low-grade inflammation (LGI) in rat model of Diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS: IBS-D model rats were established by acetic acid enema combined with restraint and tail clamping. Before EA intervention, they were divided into three groups: blank 1 group, blank 2 group, and IBS-D model group. Diarrhea symptoms and visceral pain sensitivity were evaluated. After constructed the model successfully, the remaining IBS-D model group rats were randomly divided into model group and EA group. Local intestinal inflammation (HE staining), changes of intestinal mucosa (occludin protein and microvascular diameter) were evaluated. Differences between two groups were compared using t-test or Mann-Whitney U-test. Differences among more than two groups were compared using one-way ANOVA or Kruskal-Wallis test. RESULTS: After modeling, the results of HE staining in intestinal tract of IBS-D model rats showed LGI. Compared with the model group, 4 h fecal moisture content (diarrhea index) and the AWR score were decreased in the EA group. The results of HE in EA group showed that the infiltration of intestinal inflammatory cells were alleviated. Additionally, EA significantly upregulated the expression of occludin protein and partially dilated the intestinal microvascular diameter. Pearson correlation analysis showed that the symptoms of IBS-D rats were correlated with the changes of intestinal mucosa. CONCLUSION: EA may treat intestinal LGI in IBS-D rats by upregulating the expression of occludin protein and dilating the intestinal microvascular diameter.

Head Acupuncture Plus Schuell's Language Rehabilitation for Post-Stroke Aphasia: A Systematic Review and Meta-Analysis of 32 Randomized Controlled Trials.

OBJECTIVE: To evaluate the existing randomized controlled trials (RCTs) for evidence of the efficacy and safety of head acupuncture (HA) plus Schuell's language rehabilitation (SLR) in post-stroke aphasia. METHODS: Seven databases including Embase, PubMed, Cochrane Library, Technology Periodical Database, the China National Knowledge Infrastructure, SinoMed and Wanfang Data Information Site were searched for RCTs published from database inception until November 14, 2021. RCTs that compared HA plus SLR with sham (or blank) control, acupuncture therapy alone, certain language rehabilitation therapy alone or other therapies for post-stroke aphasia were included. Data were extracted and assessed, and the quality of RCTs was evaluated. Fixed-effects model was used, with meta-inflfluence analysis, meta-regression, and regression-based sub-group analyses applied for exploration of heterogeneity. Publication bias was estimated by funnel plots and Egger's tests. RESULTS: A total of 32 RCTs with 1,968 patients were included and 51 comparisons were conducted classified as types of strokes and aphasia. (1) For patients with aphasia after ischemic stroke, HA plus PSA showed significantly higher accumulative markedly effective rate [relative risk (RR)=1.55, 95% confidence interval (CI): 1.19-2.02, I2=0%] and accumulative effective rate (RR=1.22, 95% CI: 1.09-1.36, I2=0%). (2) For patients with comprehensive types of stroke, HA plus PSA was more effective in increasing recovery rate (RR=1.89, 95% CI: 1.39-2.56, I2=0%), accumulative markedly effective rate (RR=1.53, 95% CI: 1.36-1.72, I2=9%) and accumulative effective rate (RR=1.14, 95% CI: 1.09-1.19, I2=34%). (3) For patients with aphasia after stroke, HA plus PSA was superior to PSA alone with statistical significance in increasing recovery rate (RR=2.08, 95% CI: 1.24-3.46, I2=0%), accumulative markedly effective rate (RR=1.49, 95% CI: 1.24-1.78, I2=0%) and accumulative effective rate (RR=1.15, 95% CI: 1.06-1.24, I2=39%). (4) For patients with multiple types of aphasia, HA plus PSA also demonstrated significantly higher recovery rate (RR=1.86, 95% CI: 1.28-2.72, I2=0%), accumulative markedly effective rate (RR=1.55, 95% CI: 1.35-1.78, I2=22%), and accumulative effective rate (RR=1.17, 95% CI: 1.11-1.23, I2=41%). (5) For patients with motor aphasia after ischemic stroke, compared with PSA alone, HA plus PSA showed significantly higher accumulative markedly effective rate (RR=1.38, 95% CI: 1.06-1.79, I2=0%) and accumulative effective rate (RR=1.20, 95% CI: 1.05-1.37, I2=0%). Meta-regression analyses were performed without significant difference, and publication bias was found in some comparisons. CONCLUSION: HA plus SLR was significantly associated with better language ability and higher effective rate for patients with post-stroke aphasia, and HA should be operated cautiously especially during acupuncture at eye and neck. (Registration No. CRD42020154475).

Therapeutic effects and central mechanism of acupuncture and moxibustion for treating functional dyspepsia: study protocol for an fMRI-based randomized controlled trial.

BACKGROUND: Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders, with a high prevalence and significant influence on the quality of life (QoL). Either acupuncture or moxibustion is effective for dyspepsia, which is confirmed by both ancient documents and modern research. However, the therapeutic advantage and underlying mechanism between acupuncture and moxibustion for FD remain unclear. METHODS: This randomized controlled fMRI trial aims to (i) evaluate the therapeutic advantages of acupuncture and moxibustion treatment for FD, (ii) investigate the similarities and differences in cerebral activity elicited by acupuncture and moxibustion, and (iii) analyze the possible correlations between brain responses and clinical variables thus to explore the potential central mechanism of acupuncture and moxibustion for treating FD. Ninety-two FD patients will be randomly assigned to either the acupuncture group or the moxibustion group in a 1:1 ratio. Twenty sessions of acupuncture or moxibustion treatment over 4 weeks will be performed on each patient. The short form Leeds Dyspepsia Questionnaire, the Nepean Dyspepsia Index, etc., are used to evaluate the therapeutic effects. The heart rate variability will be analyzed to investigate the autonomic nerve function. Thirty-six FD patients in each group will be randomly selected for the fMRI scan to detect cerebral activity changes. DISCUSSION: We expect the results will deepen our knowledge on the clinical value and underlying mechanism of acupuncture and moxibustion and provide a reference for a better selection of interventions for treating FD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100049496. Registered on 2 August 2021.

Supplementation of EGF, IGF-1, and Connexin 37 in IVM Medium Significantly Improved the Maturation of Bovine Oocytes and Vitrification of Their IVF Blastocysts.

The quality and developmental capacity of oocytes derived from in vitro maturation (IVM) remain unsatisfactory, which greatly impairs the efficiency and application of embryo technologies. The present experiment was designed to investigate the effect of the supplementation of EGF, IGF-1, and Cx37 in an IVM medium on the maturation quality and development ability of bovine oocytes. The cytoplasmic maturation events of oocytes and the quality of in vitro fertilization (IVF) blastocysts were examined to investigate the relative mechanisms. Our results showed that the nuclear maturation and blastocyst development after the IVF of oocytes treated with 25 µg/mL Cx37 or the combination of 50 ng/mL EGF and 100 ng/mL IGF-1 were significantly increased compared to those of the control group (p < 0.05). Furthermore, the blastocyst rate, and blastocyst total cell number and survival rate after vitrification of the EGF+IGF-1+Cx37 group, were significantly higher than those of the control group (p < 0.05), but lower than those of the FSH+LH+EGF+IGF-1+Cx37 group (p < 0.05). The transzonal projection (TZP) intensity, glutathione (GSH) level, and mitochondrial function of the EGF+IGF-1+Cx37 group were significantly higher than that of the control group, and lower than those of the FSH+LH+EGF+IGF-1+Cx37 group, in contrast to the results of the reactive oxygen species (ROS) levels. In conclusion, our results showed that the supplementation of 50 ng/mL EGF, 100 ng/mL IGF-1, and 25 µg/mL Cx37 in the IVM of bovine oocytes significantly improved their quality and developmental ability by increasing the TZP, mitochondrial function, and GSH level.

Electroacupuncture Improves Clearance of Amyloid-ß through the Glymphatic System in the SAMP8 Mouse Model of Alzheimer's Disease.

Background: Memory loss and cognitive impairment characterize the neurodegenerative disorder, Alzheimer's disease (AD). Amyloid-ß (Aß) is the key factor that triggers the course of AD, and reducing the deposition of Aß in the brain has been considered as a potential target for the treatment of AD. In clinical and animal studies, electroacupuncture (EA) has been shown to be an effective treatment for AD. In recent years, substantial evidence has accumulated suggesting the important role of the glymphatic system in Aß clearance. Objective: The purpose of this study was to explore whether EA modifies the accumulation of Aß through the glymphatic system and may thus be applied to alleviate cognitive impairments. Methods: Seven-month-old SAMP8 mice were randomized into a control group (Pc) and an electroacupuncture group (Pe). Age-matched SAMR1 mice were used as normal controls (Rc). Mice in the Pe group were stimulated on Baihui (GV20) and Yintang (GV29) for 10 min and then pricked at Shuigou (GV26) for ten times. EA treatment lasted for 8 weeks. In each week, EA would be applied once a day for the first five consecutive days and ceased at the remaining two days. After EA treatment, Morris water maze (MWM) test was used to evaluate the cognitive function; HE and Nissl staining was performed to observe the brain histomorphology; ELISA, contrast-enhanced MRI, and immunofluorescence were applied to explore the mechanisms underlying EA effects from Aß accumulation, glymphatic system function, reactivity of astrocytes, and AQP4 polarization, respectively. Results: This EA regime could improve cognition and alleviate neuropathological damage to brain tissue. And EA treatment might reduce Aß accumulation, enhance paravascular influx in the glymphatic system, inhibit the reactivity of astrocytes, and improve AQP4 polarity. Conclusion: EA treatment might reduce Aß accumulation from the brain via improving clearance performance of the glymphatic system and thereby alleviating cognitive impairment.

Regulation of Mild Moxibustion on Uterine Vascular and Prostaglandin Contents in Primary Dysmenorrhea Rat Model.

OBJECTIVE: Primary dysmenorrhea (PD) is a common and high incidence disease in gynecology, which seriously affects the quality of life in young women. Our previous study found that mild moxibustion could treat abdominal pain of PD patients, but the mechanism is still unclear. Therefore, this study aims to partly investigate the treatment mechanism of moxibustion for PD, especially on uterine microcirculation. METHODS: Forty 3-month-old Sprague Dawley female rats were randomly divided into four groups, including group A (saline control group, n = 10), group B (control plus moxibustion group, n = 10), group C (PD model group, n = 10), group D (PD. model plus moxibustion group, n = 10). The PD rat model was established by injecting estradiol benzoate and oxytocin. Mild moxibustion on Sanyinjiao (SP6) and Guanyuan (CV4) acupoints was once a day, 20 minutes per time, for 10 consecutive days. A vaginal smear was used to test the estrous cycle of rats. Uterine microvascular thickness was observed by stereomicroscope. And we detected the content of prostaglandin F2α (PGF2α ) and prostaglandin E2 (PGE2) in uterine tissue by enzyme-linked immunosorbent assay. RESULTS: Mild moxibustion can enlarge the microvessels, improve the microcirculation disturbance, and relieve the swelling of the uterus in PD rats. During the mild moxibustion intervention, the contents of PGF2α and PGE2 in uterus issues were synchronous increases or decreases and the changes of PGE2 were more obvious, but the changes of uterine microvasculature and morphology caused by the decrease of PGF2α were greater than PGE2. CONCLUSION: Mild moxibustion at SP6 and CV4 acupoints may relax uterine microvascular obstacle by reducing the content of PGF2α in uterine tissue, improve the microcirculation disorder, and then alleviate the PD rat's uterine swelling.

Traditional Chinese exercise potential role as prevention and adjuvant therapy in patients with COVID-19.

The epidemic situation of COVID-19 is a great public health emergency worldwide characterized by fastest spreading, widest infection range and the mostly difficult to prevent and control in recent years. According to medical experience, traditional Chinese exercises (TCE) have been applied for COVID-19 prevention, adjuvant treatment or rehabilitation, and achieved some curative effects. They can enhance the body immunity, improve the function of organs, especially cardiopulmonary function, promote physical and mental rehabilitation by adjusting the body, regulating the breath, regulating the mind. This paper aims to investigate the potential value of TCE for health preservation in the prevention and adjuvant treatment for COVID-19 according to an overview of application and analysis of existing evidence. On this basis, this review proposed the TCE plan by visiting clinical and practice experts, so as to provide some references for the prevention and treatment of COVID-19 with TCE in the world.

The Specific and Nonspecific Effects of Tai Chi and Its Possible Central Responses: A Protocol of Neuroimaging Study.

Tai Chi has been proven to be a safe and effective assistant therapy for healthcare and disease treatment. However, whether the adjuvant therapeutic effect of Tai Chi is general or disease-oriented remains uncertain. This trial focuses on exploring the specific and nonspecific effects of Tai Chi and its potential central responses. The results will deepen our understanding of the characteristics of Tai Chi exercise for adjuvant therapeutic effects and promote its application in the clinic. In this neuroimaging trial, 40 functional constipation (FC) patients and 40 healthy subjects (HS) will be recruited and will receive 10 weeks of Tai Chi exercise. The motor function, respiratory function, stool-related symptoms, quality of life, and emotional state of the participants will be evaluated at the baseline, the 5-week Tai Chi practice, and the end of practice. The potential changes in the heart rate variability and the cerebral function will be recorded by the 24 h dynamic electrocardiogram at the baseline and the functional magnetic resonance imaging at the end of practice. The possible correlations among the clinical variables, the heart rate variability, and the cerebral activity alterations in FC patients and HS will be analyzed. The healthcare and therapeutic effects of Tai Chi exercise might consist of the specific and nonspecific effects. This study provides not only a new perspective for understanding Tai Chi but also a new approach for investigating the mind-body exercise. This trial was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj=33243) on 28 November 2018 (registration number: ChiCTR1800019781; protocol version number: V1.0). This trial is currently in the stage of recruiting patients. The first patient was included on 1 December 2018. To date, 18 FC patients and 20 HS have been included. Recruitment will be completed in December 2020.

Electroacupuncture Pretreatment Elicits Tolerance to Cerebral Ischemia/Reperfusion through Inhibition of the GluN2B/m-Calpain/p38 MAPK Proapoptotic Pathway.

Background: As one of the first steps in the pathology of cerebral ischemia, glutamate-induced excitotoxicity progresses too fast to be the target of postischemic intervention. However, ischemic preconditioning including electroacupuncture (EA) might elicit cerebral ischemic tolerance through ameliorating excitotoxicity. Objective: To investigate whether EA pretreatment based on TCM theory could elicit cerebral tolerance against ischemia/reperfusion (I/R) injury, and explore its potential excitotoxicity inhibition mechanism from regulating proapoptotic pathway of the NMDA subtype of glutamate receptor (GluN2B). Methods: The experimental procedure included 5 consecutive days of pretreatment stage and the subsequent modeling stage for one day. All rats were evenly randomized into three groups: sham MCAO/R, MCAO/R, and EA+MCAO/R. During pretreatment procedure, only rats in the EA+MCAO/R group received EA intervention on GV20, SP6, and PC6 once a day for 5 days. Model preparation for MCAO/R or sham MCAO/R started 2 hours after the last pretreatment. 24 hours after model preparation, the Garcia neurobehavioral scoring criteria was used for the evaluation of neurological deficits, TTC for the measurement of infarct volume, TUNEL staining for determination of neural cell apoptosis at hippocampal CA1 area, and WB and double immunofluorescence staining for expression and the cellular localization of GluN2B and m-calpain and p38 MAPK. Results: This EA pretreatment regime could improve neurofunction, decrease cerebral infarction volume, and reduce neuronal apoptosis 24 hours after cerebral I/R injury. And EA pretreatment might inhibit the excessive activation of GluN2B receptor, the GluN2B downstream proapoptotic mediator m-calpain, and the phosphorylation of its transcription factor p38 MAPK in the hippocampal neurons after cerebral I/R injury. Conclusion: The EA regime might induce tolerance against I/R injury partially through the regulation of the proapoptotic GluN2B/m-calpain/p38 MAPK pathway of glutamate.