A novel intelligent model for visualized inference of medical diagnosis: A case of TCM.

How to present an intelligent model based on known diagnostic knowledge to assist medical diagnosis and display the reasoning process is an interesting issue worth exploring. This study developed a novel intelligent model for visualized inference of medical diagnosis with a case of Traditional Chinese Medicine (TCM). Four classes of TCM's diagnosis composed of Yin deficiency, Liver Yin deficiency, Kidney Yin deficiency, and Liver-Kidney Yin deficiency were selected as research examples. According to the knowledge of diagnostic points in "Diagnostics of TCM", a total of 2000 samples for training and testing were randomly generated for the four classes of TCM's diagnosis. In addition, a total of 60 clinical samples were collected from hospital clinical cases. Training samples were sent to the pre-training language model of Chinese Bert for training to generate intelligent diagnostic module. Simultaneously, a mathematical algorithm was developed to generate inferential digraphs. In order to evaluate the performance of the model, the values of accuracy, F1 score, Mse, Loss and other indicators were calculated for model training and testing. And the confusion matrices and ROC curves were plotted to estimate the predictive ability of the model. The novel model was also compared with RF and XGBOOST. And some instances of inferential digraphs with the model were displayed and analyzed. It may be a new attempt to solve the problem of interpretable and inferential intelligent models in the field of artificial intelligence on medical diagnosis of TCM.

Bacillus subtilis and Macleaya cordata extract regulate the rumen microbiota associated with enteric methane emission in dairy cows.

BACKGROUND: Ruminant livestock production is a considerable source of enteric methane (CH4) emissions. In a previous study, we found that dietary inclusions of Bacillus subtilis (BS) and Macleaya cordata extract (MCE) increased dry matter intake and milk production, while reduced enteric CH4 emission in dairy cows. The objective of this study was to further elucidate the impact of feeding BS and MCE on rumen methanogenesis in dairy cows using rumen metagenomics techniques. RESULTS: Sixty dairy cows were blocked in 20 groups of 3 cows accordingly to their live weight, milk yield, and days in milk, and within each group, the 3 cows were randomly allocated to 1 of 3 treatments: control diet (CON), control diet plus BS (BS), and control diet plus MCE (MCE). After 75 days of feeding experimental diets, 12 cows were selected from each treatment for collection of rumen samples for the metagenomic sequencing. Results showed that BS decreased ruminal acetate and butyrate, while increased propionate concentrations, resulting in decreased acetate:propionate ratio. The metagenomics analysis revealed that MCE reduced relative abundances of Methanobrevibacter wolinii, Methanobrevibacter sp. AbM4, Candidatus Methanomassiliicoccus intestinalis, Methanobrevibacter cuticularis, Methanomicrobium mobile, Methanobacterium formicicum, and Methanobacterium congolense. Both BS and MCE reduced relative abundances of Methanosphaera sp. WGK6 and Methanosphaera stadtmanae. The co-occurrence network analysis of rumen bacteria and archaea revealed that dietary treatments influenced microbial interaction patterns, with BS and MCE cows having more and stronger associations than CON cows. The random forest and heatmaps analysis demonstrated that the Halopenitus persicus was positively correlated with fat- and protein-corrected milk yield; Clostridium sp. CAG 269, Clostridium sp. 27 14, Haloarcula rubripromontorii, and Methanobrevibacter curvatus were negatively correlated with rumen acetate and butyrate concentrations, and acetate:propionate ratio, whereas Selenomonas rumiantium was positively correlated with those variables. CONCLUSIONS: The present results provided new information for mitigation of enteric methane emissions of dairy cows by feeding BS and MCE to influence rumen microbial activities. This fundamental knowledge is essential for developing enteric CH4 reduction strategies to mitigate climate change and reduce dietary energy waste. Video Abstract.

China's application of the One Health approach in addressing public health threats at the human-animal-environment interface: Advances and challenges.

Background: Due to emerging issues such as global climate change and zoonotic disease pandemics, the One Health approach has gained more attention since the turn of the 21st century. Although One Health thinking has deep roots and early applications in Chinese history, significant gaps exist in China's real-world implementation at the complex interface of the human-animal-environment. Methods: We abstracted the data from the global One Health index study and analysed China's performance in selected fields based on Structure-Process-Outcome model. By comparing China to the Belt & Road and G20 countries, the advances and gaps in China's One Health performance were determined and analysed. Findings: For the selected scientific fields, China generally performs better in ensuring food security and controlling antimicrobial resistance and worse in addressing climate change. Based on the SPO model, the "structure" indicators have the highest proportion (80.00%) of high ranking and the "outcome" indicators have the highest proportion (20.00%) of low ranking. When compared with Belt and Road countries, China scores above the median in almost all indicators (16 out of 18) under the selected scientific fields. When compared with G20 countries, China ranks highest in food security (scores 72.56 and ranks 6th), and lowest in climate change (48.74, 11th). Conclusion: Our results indicate that while China has made significant efforts to enhance the application of the One Health approach in national policies, it still faces challenges in translating policies into practical measures. It is recommended that a holistic One Health action framework be established for China in accordance with diverse social and cultural contexts, with a particular emphasis on overcoming data barriers and mobilizing stakeholders both domestically and globally. Implementation mechanisms, with clarified stakeholder responsibilities and incentives, should be improved along with top-level design.

Huoxin Pill Reduces Myocardial Ischemia Reperfusion Injury in Rats via TLR4/NFκB/NLRP3 Signaling Pathway.

OBJECTIVE: To explore the protective effect of Huoxin Pill (HXP) on acute myocardial ischemia-reperfusion (MIRI) injury in rats. METHODS: Seventy-five adult SD rats were divided into the sham-operated group, model group, positive drug group (diltiazem hydrochloride, DH), high dose group (24 mg/kg, HXP-H) and low dose group (12 mg/kg, HXP-L) of Huoxin Pill (n=15 for every group) according to the complete randomization method. After 1 week of intragastric administration, the left anterior descending coronary artery of the rat's heart was ligated for 45 min and reperfused for 3 h. Serum was separated and the levels of creatine kinase (CK), creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA), hypersensitive C-reactive protein (hs-CRP) and interleukin-1ß (IL-1ß) were measured. Myocardial ischemia rate, myocardial infarction rate and myocardial no-reflow rate were determined by staining with Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC). Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN) databases were used to screen for possible active compounds of HXP and their potential therapeutic targets; the results of anti-inflammatory genes associated with MIRI were obtained from GeneCards, Drugbank, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Datebase (TTD) databases was performed; Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to analyze the intersected targets; molecular docking was performed using AutoDock Tools. Western blot was used to detect the protein expression of Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NFκB)/NOD-like receptor protein 3 (NLRP3). RESULTS: Compared with the model group, all doses of HXP significantly reduced the levels of LDH, CK and CK-MB (P<0.05, P<0.01); HXP significantly increased serum activity of SOD (P<0.05, P<0.01); all doses of HXP significantly reduced the levels of hs-CRP and IL-1ß (P<0.05, P<0.01) and the myocardial infarction rate and myocardial no-reflow rate (P<0.01). GO enrichment analysis mainly involved positive regulation of gene expression, extracellular space and identical protein binding, KEGG pathway enrichment mainly involved PI3K-Akt signaling pathway and lipid and atherosclerosis. Molecular docking results showed that kaempferol and luteolin had a better affinity with TLR4, NFκB and NLRP3 molecules. The protein expressions of TLR4, NFκB and NLRP3 were reduced in the HXP group (P<0.01). CONCLUSIONS: HXP has a significant protective effect on myocardial ischemia-reperfusion injury in rats, and its effect may be related to the inhibition of redox response and reduction of the inflammatory response by inhibiting the TLR4NFκB/NLRP3 signaling pathway.

[Processing Magnoliae Officinalis Cortex with ginger juice: process optimization based on AHP-CRITIC weighting method and composition changes after processing].

The weight coefficients of appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol were determined by analytic hierarchy process(AHP), criteria importance though intercrieria correlation(CRITIC), and AHP-CRITIC weighting method, and the comprehensive scores were calculated. The effects of ginger juice dosage, moistening time, proces-sing temperature, and processing time on the quality of Magnoliae Officinalis Cortex(MOC) were investigated, and Box-Behnken design was employed to optimize the process parameters. To reveal the processing mechanism, MOC, ginger juice-processed Magnoliae Officinalis Cortex(GMOC), and water-processed Magnoliae Officinalis Cortex(WMOC) were compared. The results showed that the weight coefficients of the appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol determined by AHP-CRITIC weighting method were 0.134, 0.287, and 0.579, respectively. The optimal processing parameters of GMOC were ginger juice dosage of 8%, moistening time of 120 min, and processing at 100 ℃ for 7 min. The content of syringoside and magnolflorine in MOC decreased after processing, and the content of honokiol and magnolol followed the trend of GMOC>MOC>WMOC, which suggested that the change in clinical efficacy of MOC after processing was associated with the changes of chemical composition. The optimized processing technology is stable and feasible and provides references for the modern production and processing of MOC.

[Optimization of extraction process of Chuanxiong Rhizoma-Gastrodiae Rhizoma based on network pharmacology and multi-index orthogonal test].

To optimize the extraction process of Chuanxiong Rhizoma-Gastrodiae Rhizoma herb pair by network pharmacology combined with analytic hierarchy process(AHP)-entropy weight method and multi-index orthogonal test. The potential active components and targets of Chuanxiong Rhizoma-Gastrodiae Rhizoma were screened by network pharmacology and molecular docking, and the process evaluation indexes were determined with reference to the Chinese Pharmacopoeia(2020 edition). The core components of Chuanxiong Rhizoma-Gastrodiae Rhizoma were determined as gastrodin, parishin B, parishin C, parishin E, ferulic acid, and 3-butylphthalide. With the extraction volume of each indicator and yield of dry extract as comprehensive evaluation indicators, the extraction conditions were optimized by the AHP-entropy weight method and orthogonal test as the ethanol volume of 50%, the solid-liquid ratio of 1∶8(g·mL~(-1)), extraction for three times, and 1.5 h each time. Through network pharmacology and molecular docking, the process evaluation index was determined, and the optimized process was stable and reproducible for the extraction of Chuanxiong Rhizoma-Gastrodiae Rhizoma herb pair, which could provide reference for in-depth research.

First report of jujube anthracnose caused by Colletotrichum siamense in China.

Jujube (Zizyphus jujuba Mill.), a native small deciduous tree of China, is widely cultivated in China, Korea, India, Japan, Europe, and the United States (Chen et al. 2020). The fruit have been commonly consumed as healthy food supplements and traditional Chinese medicine for over 2000 years (Li et al. 2007). In August 2019, anthracnose-like leaf spot symptoms were observed on jujube plants in Xiaomenya Village, Jinan City, Shandong Province, China (36°27'39″N, 117°3'13″E), with over 30% leaf disease incidence. The spots were circular, sunken, brown in the center and with dark brown edges. As the spots enlarged and coalesced, it resulted in leaf perforation and early defoliation. Sometimes acervuli were observed on the lesions (Fig. S1a, b). To identify the causal agent, 20 diseased leaves were sampled, the margins of the lesions were cut into pieces (5 × 5 mm), sterilized and cultured following the protocol described previously (Wan et al. 2020) at 25 ℃ for 5 days. Twelve monospore isolates showing identical colony morphology were obtained. Three representative isolates, JNZG11, JNZG311, JNZG313, were used for further study. When grown on PDA the colony color was initially white and then turned pale-gray to gray in 5-day-old cultures. On the reverse, colonies were brown-black with an orange pigmentation near the center. Aerial mycelium was cottony, dense, white to pale-gray. Conidia were hyaline, 1-celled, smooth-walled, subcylindrical, oblong, attenuated with slightly rounded ends, (11.1-) 12.7-13.3 (-17.8) ×(-4.4) 5.2-5.5 (-6.3) µm (n=50). Appressoria were dark-brown, oval or irregular, (7.3-) 8.6-9.2 (-9.8) ×(-5.1) 5.8-6.9 (-7.0) µm (n=50) (Fig. S1c-g). The morphology resembled those of Colletotrichum gloeosporioides species complex (Cannon et al. 2012). For accurate identification, the sequences of the ribosomal internal transcribed spacer (ITS), actin (ACT), ß-tub2 (TUB2), calmodulin (CAL), chitin synthase (CHS-1), and glyceraldehyde-3phosphate dehydrogenase (GAPDH) of the 3 isolates were sequenced (Weir et al. 2012), and deposited into GenBank (Accession Nos. see Table 1). The six loci (ITS, GAPDH, ACT, CHS-1, CAL, and TUB2) were concatenated and the aligned sequences (1904 bp) were 99.7% homologous to ex-type C. siamense ICMP18578. The sequences of 38 Colletotrichum species (44 isolates) were downloaded from GenBank for phylogenetic analyses. In the maximum likelihood phylogenetic tree generated, the highest log likelihood was -8798.90 and the three isolates were all in the C. siamense clade (bootstrap support 94 %) (Fig. S2). To complete Koch's postulates, 60 healthy, mature jujube leaves on 12 branches (5 leaves per branch) (variety 'Zhongqiuhong') were inoculated with 20 µL of spore suspension (106 conidia/mL) or sterile water as a control. The branches were placed in sterile beakers containing a small amount of sterile water sealed with plastic wrap and maintained at 28 °C, 12 h light/dark. Five days after inoculation, all treated leaves showed the typical anthracnose symptom, similar to that observed in the field (Fig. S1h). The same fungus was re-isolated from the margins of the lesions using the aforementioned methods. Whereas no fungus were isolated from the controls. Previously, C. siamense has been reported to infect Z. mauritiana in China (Shu et al. 2020). To our knowledge, this is the first report of C. siamense causing anthracnose on Z. jujuba in China. This finding provides crucial information for the effective management of this disease.

Gene coexpression networks allow the discovery of two strictosidine synthases underlying monoterpene indole alkaloid biosynthesis in Uncaria rhynchophylla.

Plant-derived monoterpene indole alkaloids (MIAs) from Uncaria rhynchophylla (UR) have huge medicinal properties in treating Alzheimer's disease, Parkinson's disease, and depression. Although many bioactive UR-MIA products have been isolated as drugs, their biosynthetic pathway remains largely unexplored. In this study, untargeted metabolome identified 79 MIA features in UR tissues (leaf, branch stem, hook stem, and stem), of which 30 MIAs were differentially accumulated among different tissues. Short time series expression analysis captured 58 pathway genes and 12 hub regulators responsible for UR-MIA biosynthesis and regulation, which were strong links with main UR-MIA features. Coexpression networks further pointed to two strictosidine synthases (UrSTR1/5) that were coregulated with multiple MIA-related genes and highly correlated with UR-MIA features (r > 0.7, P < 0.005). Both UrSTR1/5 catalyzed the formation of strictosidine with tryptamine and secologanin as substrates, highlighting the importance of key residues (UrSTR1: Glu309, Tyr155; UrSTR5: Glu295, Tyr141). Further, overexpression of UrSTR1/5 in UR hairy roots constitutively increased the biosynthesis of bioactive UR-MIAs (rhynchophylline, isorhynchophylline, corynoxeine, etc), whereas RNAi of UrSTR1/5 significantly decreased UR-MIA biosynthesis. Collectively, our work not only provides candidates for reconstituting the biosynthesis of bioactive UR-MIAs in heterologous hosts but also highlights a powerful strategy for mining natural product biosynthesis in medicinal plants.

Review and reflection on the development of Traditional Chinese Medicine meridian theory / 国际中医中药杂志

The meridian theory is the pioneer of clinical diagnosis and treatment of diseases in Traditional Chinese Medicine (TCM). From Shang Han Lun to Pi Wei Lun, the meridian theory has contributed important theoretical organization materials and clinical practice experience to the establishment of the diagnosis system of external and internal injuries. The acupoints contained in its clinical acupuncture and moxibustion record symptoms, and some laws summarized have been absorbed and used for reference. It shows the positive significance of its exploration in clinical diagnosis and treatment. A system of differentiation and treatment of external and internal injuries with acupuncture has not been formed, even though the meridian theory of TCM has a long history with many areas being explored, such as diseases, acupoints, acupuncture methods and stimulation amount. Therefore, this paper starts from the academic development history of meridians, reviews and analyzes the contribution and limitations of TCM acupuncture and moxibustion in the diagnosis and treatment of internal injury, in order to enlighten the current study and understanding of TCM.

Evaluation of lncRNA FOXD3-AS1 as a Biomarker for Early-Stage Lung Cancer Diagnosis and Subtype Identification.

Purpose: Lung cancer (LC) is the most commonly diagnosed cancer and the leading cause of cancer-related deaths. More and more long noncoding RNA (lncRNA) are associated with cancer. This study aimed to assess whether plasma lncRNA could be used to diagnose early-stage LC and identify subtypes of LC. Methods: For bioinformatic analysis, we used genetic data from the Cancer Genome Atlas, lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC) datasets and a small cell lung cancer (SCLC) dataset from the Gene Expression Omnibus. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to examine the relative expression of lncRNA in LC tissues and plasma samples. The patients' clinical information was obtained at the time of sample collection. Results: According to public datasets, the lncRNA forkhead box D3 antisense 1 (FOXD3-AS1) was significantly upregulated in LUAD, LUSC, and SCLC tissues over controls. RT-qPCR assays confirmed this finding in LUAD, LUSC, and SCLC tissues and plasma samples. Even early-stage receiver operating characteristic analysis showed that plasma FOXD3-AS1 could be used to discriminate LUAD, LUSC, and SCLC from normal controls and identify LC subtypes SCLC. Conclusion: FOXD3-AS1 is significantly upregulated in LC tissues and plasma. FOXD3-AS1 could be a potential biomarker for LC subtype identification and early diagnosis.

Mapping thalamic-anterior cingulate monosynaptic inputs in adult mice.

The anterior cingulate cortex (ACC) is located in the frontal part of the cingulate cortex, and plays important roles in pain perception and emotion. The thalamocortical pathway is the major sensory input to the ACC. Previous studies have show that several different thalamic nuclei receive projection fibers from spinothalamic tract, that in turn send efferents to the ACC by using neural tracers and optical imaging methods. Most of these studies were performed in monkeys, cats, and rats, few studies were reported systematically in adult mice. Adult mice, especially genetically modified mice, have provided molecular and synaptic mechanisms for cortical plasticity and modulation in the ACC. In the present study, we utilized rabies virus-based retrograde tracing system to map thalamic-anterior cingulate monosynaptic inputs in adult mice. We also combined with a new high-throughput VISoR imaging technique to generate a three-dimensional whole-brain reconstruction, especially the thalamus. We found that cortical neurons in the ACC received direct projections from different sub-nuclei in the thalamus, including the anterior, ventral, medial, lateral, midline, and intralaminar thalamic nuclei. These findings provide key anatomic evidences for the connection between the thalamus and ACC.

Isoflavones from Sojae Semen Praeparatum Regulate Lipid Metabolism in Atherosclerotic Mice Through PPARγ/LXRα/ABCA1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the effect of isoflavones from Sojae Semen Praeparatum （ISSP） on lipid metabolism in atherosclerotic mice， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor gamma/liver X receptor alpha/ATP-binding cassette transporter A1 （PPARγ/LXRα/ABCA1） signaling pathway. MethodFifty ApoE-/- mice were randomly assigned into the model group， western medicine （atorvastatin calcium， 3.03 mg·kg-1） group， and low-， medium-， and high-dose ISSP （2.5， 5， 10 mg·kg-1， respectively） groups， with 10 rats in each group. Atherosclerosis model mice were established by bilateral ovariectomy and feeding high-fat diet. Another 10 ApoE-/- mice receiving ovariectomy and high-fat diet were taken as the sham group. Some mice died of postoperative infection， and finally 6 mice were included in each group. One week after operation， each group was administrated with corresponding drugs or equivalent amount of normal saline. After 12 weeks， the levels of triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and non-esterified fatty acids （NEFAs） in serum and liver tissue were measured. The levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining and oil red O staining were used for observation of aortic plaque formation and liver lipid deposition. The mRNA and protein levels of PPARγ， LXRα， ABCA1， and ATP-binding cassette transporter G1 （ABCG1） in liver were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the sham group， the modeling of atherosclerosis increased the aortic plaque area （P<0.01）， elevated the serum TC， TG， LDL-C， TNF-α， and IL-6 levels （P<0.01）， decreased the level of HDL-C （P<0.01）， increased the liver index （P<0.05） and the levels of TC， TG， and NEFAs in liver （P<0.01）， and caused obvious hepatic fat vacuoles and lipid deposition. In addition， the modeling down-regulated the mRNA levels of PPARγ， LXRα， ABCA1 in liver （P<0.05， P<0.01），and regulated the mRNA and protein levels of ABCG1（P<0.05， P<0.01）. Compared with the model group， atorvastatin calcium and middle-， high-dose ISSP reduced the serum TC， TG， LDL-C， TNF-α， and IL-6 levels （P<0.01）， decreased the liver index （P<0.01）， alleviated the liver fat vacuoles and lipid deposition， and increased the levels of TC， TG， and NEFAs in the liver （P<0.05， P<0.01）. Furthermore， they up-regulated the mRNA and protein levels of PPARγ， LXRα， ABCA1， and ABCG1 in the liver （P<0.05， P<0.01）. ConclusionISSP may regulate lipid metabolism through PPARγ/LXRα/ABCA1 signaling pathway to down-regulate the expression of inflammatory cytokines in serum and alleviate liver lipid deposition， thereby suppressing the formation of atherosclerotic plaque.

[Effect of nape cluster acupuncture on swallowing function and respiratory function in patients with post-stroke dysphagia].

OBJECTIVE: To observe the effect of nape cluster acupuncture on swallowing function and respiratory function in patients with post-stroke dysphagia, and to explore its relationship to cerebral arterial flow and neurotrophic factors. METHODS: A total of 120 patients with post-stroke dysphagia were randomized into an observation group and a control group, 60 patients in each one. The conventional swallowing rehabilitation therapy and respiratory function training were adopted in the control group. On the basis of treatment in the control group, nape cluster acupuncture was applied at Fengchi (GB 20), Tianzhu (BL 10), Wangu (GB 12), Lianquan (CV 23), Panglianquan (Extra), once a day; pricking blood was applied at Jinjin (EX-HN 12) and Yuye (EX-HN 13), once every 2 days. Both groups were treated for 2 weeks. The therapeutic efficacy was compared between the two groups, and the swallowing function (scores of Kubota water swallowing test, standardized swallowing assessment [SSA] and video fluoroscopic swallowing study [VFSS]), the respiratory function indexes (forced vital capacity [FVC], maximal voluntary ventilation [MVV] and maximal expiratory time), the bilateral cerebral arterial hemodynamics parameters (systolic peak velocity [Vs], mean flow velocity [Vm] and vascular resistance index [RI]) and the serology indexes (brain-derived neurotrophic factor [BDNF], nerve growth factor [NGF] and insulin-like growth factors-1 [IGF-1]) before and after treatment were observed in the both groups. RESULTS: The total effective rate was 80.0% (48/60) in the observation group, which was superior to 60.0% (36/60) in the control group (P<0.05). After treatment, the scores of Kubota water swallowing test and SSA in the observation group were lower than the control group (P<0.05), the VFSS score, FVC, MVV and maximal expiratory time were higher than the control group (P<0.05). After treatment, the Vs and Vm of bilateral cerebral artery and serum levels of BDNF, NGF and IGF-1 in the observation group were higher than the control group (P<0.05), the RI of bilateral cerebral artery was lower than the control group (P<0.05). CONCLUSION: On the basis of the conventional rehabilitation training, nape cluster acupuncture can effectively improve the swallowing function and respiratory function in patients with post-stroke dysphagia, its mechanism may be related to the improvement of cerebral hemodynamics and the regulation of neurotrophic factors.

[Professor WU Xu's experience in treatment of tic disorders in children with acupuncture from "meridian tendons"].

Professor WU Xu believes that the pathogenesis of tic disorders in children is "agitation of liver wind, lending to excessive wind and spasm of tendons" "deficiency of yin fluid, the tendons failing to be nourished" "spirit failing to govern, leading to tendons not be restrained" and advocates to treat this disease from the theory of "meridian tendons". He suggests the acupoints that related to "meridian tendons", and emphasizes the depth of needling and the procedure of acupuncture, and believes that the core of treating is to balance the yin and yang of "meridian tendons" and regulate spirit.

Effect and safety of acupuncture for autism spectrum disorders: A protocol for systematic review and meta-analysis.

BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition, which is characterized by impairment in social interaction or communication and lack of flexibility of imagination and behavior. Acupuncture is one of the most common modality of Traditional Chinese medicine (TCM) and has been used to treat various disease in clinical practice for more than 2000 years in China by correcting disharmony and dysregulation of body. It has sometimes been used as a treatment aimed at improving ASD symptoms and outcomes, but its clinical effectiveness and safety has not been rigorously reviewed. We will plan to conduct a systematic review and meta-analysis to summarize the current evidence on the effects and safety of acupuncture for ASD. METHODS: The following databases will be searched: PubMed, the Cochrane Library, Embase, Wanfang Data, China National Knowledge Infrastructure, SinoMed, and VIP. Randomised controlled trials will be included to evaluate the effect and safety of acupuncture on patients with ASD. The primary outcome will be the core features of ASD. The risk of bias will be assessed by the Cochrane risk of bias tool. We will conduct a meta-analysis and sensitivity analysis, as well as a subgroup analysis if high heterogeneity is present, using Revman 5.3. We will use funnel plots to identify potential reporting biases. The Grading of Recommendations Assessment, Development and Evaluation will be used to evaluate the quality of evidence. RESULTS: This study will be to assess the effect and safety of acupuncture for ASD. CONCLUSIONS: This study will assess the effect of acupuncture for ASD and provide reliable evidence for the choice of treatments. ETHICS AND DISSEMINATION: The protocol will not need ethical approval because no issues of participant privacy exist. The results of this systematic review will provide evidence about the effect and safety of acupuncture for ASD. The results will be disseminated through peer review.

Wnt/ß­catenin signaling modulates piperine­mediated antitumor effects on human osteosarcoma cells.

The plant extract piperine is used as a traditional Chinese medicine due to its anti­inflammatory effects and efficacy against numerous types of cancer. The aim of the present study was to investigate the antitumor mechanism of piperine in human osteosarcoma U2OS and 143B cell lines. The effects of piperine on cell apoptosis and invasion of human osteosarcoma cells were assessed using flow cytometry and Transwell assays. Moreover, western blotting was used to measure the effects of piperine on the protein expression levels of the metastasis markers matrix metalloproteinase­2 (MMP­2) and vascular endothelial growth factor (VEGF). In addition, the involvement of the Wnt/ß­catenin signaling pathway in modulating the effects of piperine was examined via western blot analysis. The results of MTT and Transwell invasion assays indicated that piperine treatment dose­dependently reduced U2OS and 143B cell viability and invasion. Furthermore, a significant reduction was identified in MMP­2, VEGF, glycogen synthase kinase­3ß and ß­catenin protein expression levels, as well as the expression levels of their target proteins cyclooxygenase­2, cyclin D1 and c­myc, in U2OS cells after piperine treatment. In addition, similar results were observed in 143B cells. Therefore, the present study demonstrated the efficacy of piperine in osteosarcoma, and identified that the Wnt/ß­catenin signaling pathway may modulate the antitumor effects of piperine on human U2OS and 143B cells.

Synergistic neuroprotective effect of schisandrin and nootkatone on regulating inflammation, apoptosis and autophagy via the PI3K/AKT pathway.

Alzheimer's disease (AD) is a neurodegenerative disease that seriously threatens elderly health. Schisandrin (SCH) and nootkatone (NKT) are two core components derived from Alpinia oxyphylla-Schisandra chinensis herb pair (ASHP), a traditional Chinese medicine formulation. Previous studies demonstrated that the combination of NKT and SCH exerted a neuroprotective effect in AD mouse models. The present study was undertaken to investigate whether there was a synergistic effect between NKT and SCH and the possible mechanism in Aß1-42 induced PC12 cells. SCH (50 µM) and NKT (10 µM) had the most notable inhibitory effect on the level of Aß secreted by cells. Treatment with NKT + SCH activated the PI3K/AKT/Gsk-3ß/mTOR pathway. Inflammation related proteins such as NF-κB, IKK, IL-1ß, IL-6 and TNF-α were decreased. The levels of cleaved-Caspase3 and LC3-II were reduced, indicating that apoptosis and autophagy were inhibited. These results revealed that NKT + SCH exerted a neuroprotective effect via the PI3K/AKT pathway, inhibiting inflammation, apoptosis and autophagy.

Alpinia oxyphylla-Schisandra chinensis Herb Pair Alleviates Amyloid-ß Induced Cognitive Deficits via PI3K/Akt/Gsk-3ß/CREB Pathway.

Alzheimer's disease (AD), one of the most common neurodegenerative diseases, threatens people's health. Based on the theory of traditional Chinese medicine (TCM) efficacy and treatment theory, we first proposed the Alpinia oxyphylla-Schisandra chinensis herb pair (ASHP) for finding a candidate of AD treatment. This study aimed at exploring the effects of ASHP on improving the cognitive function and neurodegeneration, and revealing the possible mechanism. In this study, an amyloid-ß (Aß) induced AD model was established in mice via intracerebroventricular injection. The Y-maze test and Morris water maze test were carried out to observe the behavioral change of mice, which showed that ASHP significantly ameliorated cognitive impairment. In addition, ASHP reduced amyloid-ß deposition and downregulated the hyperphosphorylation of tau via immunofluorescence assay and western blot analysis, respectively. Subsequently we focused on the PI3K/Akt pathway that is a classical pathway related to nervous system diseases. It also noticeably ASHP improved the histopathological changes in the hippocampus and cortex. Moreover, it was found that ASHP could upregulate the PI3K/Akt/Gsk-3ß/CREB signaling pathway in N2a-SwedAPP cells. Taken together, it suggests that ASHP might reverse cognitive deficits and neurodegeneration via PI3K/Akt/Gsk-3ß/CREB pathway.

Heterogeneity of nutrition care procedures in nutrition guidelines for cancer patients.

OBJECTIVES: The aim of this study was to systematically assess the nutrition care procedures in nutrition guidelines for cancer patients and identify gaps limiting evidence-based practise. METHODS: A systematic search of databases and websites was conducted to identify nutrition guidelines for cancer patients. The quality of the eligible guidelines was evaluated by using the Appraisal of Guidelines for Research and Evaluation (AGREE II). The Measurement Scale of Rate of Agreement (MSRA) was used to assess the scientific agreement of formulated recommendations for nutrition care procedures in the guidelines (2017-2019), and evidence supporting these recommendations was extracted and analysed. RESULTS: Seventeen nutrition guidelines for cancer patients were identified. Only European Society for Clinical Nutrition and Metabolism (ESPEN) and Australian guidelines have a total quality score of more than 60%, which is worthy of clinical recommendation. Twelve guidelines (2017-2019) were included to further analyse the heterogeneity and causes of nutrition care procedures, and we found that the content and tools of nutrition screening and assessment, the application of immune nutrients, and the selection of nutritional support pathways were heterogeneous. The main reasons for the heterogeneity of nutrition care procedures were insufficient attention to nutrition risk screening, differences in recommendations for nutrition assessment, immune nutrients and nutritional support, unreasonable citation of screening and assessment evidence, preference of developers, and lack of evidence of high-quality research on energy and nitrogen demand. In addition, the fairness and propensity of the guidelines for the selection of evidence for different cancer patients are also potential reasons for the heterogeneity of nutritional care procedures. CONCLUSIONS: The quality of the nutrition guidelines for cancer patients was highly variable. The nutrition care procedures were heterogeneous among the different guidelines in the last 3 years. Specific improvement of the factors leading to the heterogeneity of nutrition care procedures will be a reasonable and effective way for developers to upgrade the nutrition care procedures in the guidelines for cancer patients.

Comparative pharmacokinetic study of the components in Alpinia oxyphylla Miq.-Schisandra chinensis (Turcz.) Baill. herb pair and its single herb between normal and Alzheimer's disease rats by UPLC-MS/MS.

Alzheimer's disease (AD) is a neurodegenerative disease that seriously affects daily life. Schisandra chinensis (Turcz.) Baill. Fructus (SCF) and Alpinia oxyphylla Miq. Fructus (AOF) have been regarded as classical herbs for dementia since ancient times. Alpinia oxyphylla Miq.-Schisandra chinensis (Turcz.) Baill. herb pair (ASHP) is the compatible form of the two herbs. Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established for the simultaneous determination of protocatechuic acid, chrysin, schisandrin, gomisin A, gomisin B, nootkatone, deoxyschizandrin, schisandrin B and schisandrin C in rat plasma. The pharmacokinetic differences of the above nine active components in normal rats and AD model rats after oral administration of SCF, AOF, and ASHP ethanol extracts were investigated. Chloramphenicol and bifendate were used as the internal standards. Extraction of plasma sample was by liquid-liquid extraction with ethyl acetate. A SBC18 column (2.1 mm × 100 mm, 1.8 µm) was used in this experiment at a flow rate of 0.3 mL/min at 30 °C with linear gradient elution using acetonitrile and water containing 0.1% formic acid. This study showed ASHP can improve the absorption of protocatechuic acid, chrysin, schisandrin, gomisin B, nootkatone, deoxyschizandrin, schisandrin B and schisandrin C in vivo and slow down part of these components' elimination. In addition, compared with normal rats, the pharmacokinetic parameters changed significantly in AD model rats' plasma after oral administration of ASHP. Hence, these may be the pharmacokinetic mechanism of ASHP, in addition to serving as a potential agent in the treatment of AD.