Natural hyperoside extracted from hawthorn exhibits antiviral activity against porcine epidemic diarrhea virus in vitro and in vivo.

Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and death in piglets, resulting in significant economic losses for the pork industry. There is an urgent need for new treatment strategies. Here, we focused on optimizing the process of purifying natural hyperoside (nHYP) from hawthorn and evaluating its effectiveness against PEDV both in vitro and in vivo. Our findings demonstrated that nHYP with a purity >98% was successfully isolated from hawthorn with an extraction rate of 0.42 mg/g. Furthermore, nHYP exhibited strong inhibitory effects on PEDV replication in cells, with a selection index of 9.72. nHYP significantly reduced the viral load in the intestines of piglets and protected three of four piglets from death caused by PEDV infection. Mechanistically, nHYP could intervene in the interaction of PEDV N protein and p53. The findings implicate nHYP as having promising therapeutic potential for combating PEDV infections.

Ablation of Brg1 in fibroblast/myofibroblast lineages attenuates renal fibrosis in mice with diabetic nephropathy.

AIMS: Diabetic nephropathy (DN) is one of the most common complications of diabetes and represents a prototypical form of chronic kidney disease (CKD). Interstitial fibrosis is a key pathological feature of DN. During DN-associated renal fibrosis, resident fibroblasts trans-differentiate into myofibroblasts to remodel the extracellular matrix, the underlying epigenetic mechanism of which is not entirely clear. METHODS: Diabetic nephropathy was induced in C57B6/j mice by a single injection with streptozotocin (STZ). Gene expression was examined by quantitative PCR and Western blotting. Renal fibrosis was evaluated by PicroSirius Red staining. RESULTS: We report that expression of Brg1, a chromatin remodeling protein, in renal fibroblasts was up-regulated during DN pathogenesis as assessed by single-cell RNA-seq. Treatment with high glucose similarly augmented Brg1 expression in primary renal fibroblasts in vitro. Importantly, Brg1 ablation in quiescent renal fibroblasts or in mature myofibroblasts equivalently attenuated renal fibrosis in the context of diabetic nephropathy in mice. Additionally, administration with a small-molecule Brg1 inhibitor PFI-3 ameliorated renal fibrosis and improved renal function in mice induced to develop DN. SIGNIFICANCE: In conclusion, our data provide novel genetic evidence that links Brg1 to fibroblast-myofibroblast transition and renewed rationale for targeting Brg1 in the intervention of DN-associated renal fibrosis.

Suv39h1 contributes to activation of hepatic stellate cells in non-alcoholic fatty liver disease by enabling anaerobic glycolysis.

AIMS: Non-alcoholic fatty liver disease (NAFLD) has become a global epidemic. Excessive fibrogenesis, characterized by activation of hepatic stellate cells (HSCs), is a hallmark event in late stages of NAFLD. HSC activation is metabolically programmed by anaerobic glycolysis. In the present study we investigated the involvement of suppressor of variegation 3-9 homolog 1 (Suv39h1), a lysine methyltransferase, in NAFLD-associated liver fibrosis. METHODS AND MATERIALS: Liver fibrosis was induced by feeding the mice with a methionine-and-choline deficient (MCD) diet for 8 weeks. RESULTS: We report that germline deletion of Suv39h1 attenuated liver fibrosis in mice fed an MCD diet. In addition, HSC conditional deletion of Suv39h1 similarly ameliorated liver fibrosis in the NAFLD mice. Interestingly, co-culturing with hepatocytes exposed to palmitate promoted glycolysis in wild type HSCs but not in Suv39h1 deficient HSCs. Mechanistically, Suv39h1 facilitated the recruitment of hypoxia induced factor (HIF-1α) to stimulate the transcription of hexokinase 2 (HK2) in HSCs thereby enhancing glycolysis. Importantly, a positive correlation between Suv39h1, HK2, and myofibroblast markers was identified in liver specimens from NAFLD patients. SIGNIFICANCE: In conclusion, our data identify a novel pathway that contributes to the liver fibrosis and points to the possibility of targeting Suv39h1 for the intervention of liver fibrosis in NAFLD.

The chromatin remodeling protein BRG1 mediates Ang II induced pro-fibrogenic response in renal fibroblasts.

AIMS: Renal fibrosis is an important pathophysiological process commonly observed in patients chronic kidney disease (CKD). Angiotensin II (Ang II) is a major risk factor for CKD in part by promoting renal fibrosis. In the present study we investigated Brahma-Related Gene 1 (BRG1, encoded by Smarca4) in Ang II induced pro-fibrogenic response in renal fibroblasts. METHODS AND MATERIALS: CKD was induced by chronic angiotensin II infusion. Fibroblast- and myofibroblast-specific BRG1 deletion was achieved by crossing the BRG1f/f mice to the Col1a1-CreERT2 mice and the Postn-CreERT2 mice, respectively. KEY FINDINGS: BRG1 expression was up-regulated when fibroblasts were exposed to Ang II in vitro and in vivo. BRG1 silencing in primary renal fibroblasts blocked transition to myofibroblasts as evidenced by down-regulation of myofibroblast marker genes and reduction in cell proliferation, migration, and contraction. Consistently, deletion of BRG1 from fibroblasts or from myofibroblasts significantly attenuated renal fibrosis in mice subjected to chronic Ang II infusion. Transcriptomic analysis indicated that BRG1 primarily regulated expression of genes involved in cell migroproliferative behavior and extracellular matrix remodeling. Importantly, administration of PFI-3, a small-molecule BRG1 inhibition, markedly ameliorated Ang II induced renal fibrosis in mice. SIGNIFICANCE: Our data support a role for BRG1 in Ang II induced fibrogenic response in renal fibroblasts and suggest that targeting BRG1 could be considered as a reasonable approach for the intervention of CKD.

A survey of fecal virome and bacterial community of the diarrhea-affected cattle in northeast China reveals novel disease-associated ecological risk factors.

Limited information on the virome and bacterial community hampers our ability to discern systemic ecological risk factors that cause cattle diarrhea, which has become a pressing issue in the control of disease. A total of 110 viruses, 1,011 bacterial genera, and 322 complete viral genomes were identified from 70 sequencing samples mixed with 1,120 fecal samples from 58 farms in northeast China. For the diarrheic samples, the identified virome and bacterial community varied in terms of composition, abundance, diversity, and geographic distribution in relation to different disease-associated ecological factors; the abundance of identified viruses and bacteria was significantly correlated with the host factors of clinical status, cattle type, and age, and with environmental factors such as aquaculture model and geographical location (P < 0.05); a significant interaction occurred between viruses and viruses, bacteria and bacteria, as well as between bacteria and viruses (P < 0.05). The abundance of SMB53, Butyrivibrio, Facklamia, Trichococcus, and Turicibacter was significantly correlated with the health status of cattle (P < 0.05). The proportion of BRV, BCoV, BKV, BToV, BoNoV, BoNeV, BoAstV, BEV, BoPV, and BVDV in 1,120 fecal samples varied from 1.61% to 12.05%. A series of significant correlations were observed between the prevalence of individual viruses and the disease-associated ecological factors. A genome-based phylogenetic analysis revealed high variability of 10 bovine enteric viruses. The bovine hungarovirus was initially identified in both dairy and beef cattle in China. This study elucidates the fecal virome and bacterial community signatures of cattle affected by diarrhea, and reveals novel disease-associated ecological risk factors, including cattle type, cattle age, aquaculture model, and geographical location.IMPORTANCEThe lack of data on the virome and bacterial community restricts our capability to recognize ecological risk factors for bovine diarrhea disease, thereby hindering our overall comprehension of the disease's cause. In this study, we found that, for the diarrheal samples, the identified virome and bacterial community varied in terms of composition, abundance, diversity, configuration, and geographic distribution in relation to different disease-associated ecological factors. A series of significant correlations were observed between the prevalence of individual viruses and the disease-associated ecological factors. Our study aims to uncover novel ecological risk factors of bovine diarrheal disease by examining the pathogenic microorganism-host-environment disease ecology, thereby providing a new perspective on the control of bovine diarrheal diseases.

Four kinds of traditional Chinese exercise therapy in the treatment of type 2 diabetes: a systematic review and network meta-analysis.

OBJECTIVE: To perform an evidence-based evaluation of the clinical efficacy of Taijiquan, Baduanjin, Yijinjing and Wuqinxi in interventions for type 2 diabetes. DESIGN: A systematic review and network meta-analysis. METHODS: The comprehensive search included Chinese and other language databases such as the MEDLINE (PubMed), Web of Science, Excerpta Medica Database (Embase), The Cochrane Library, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China Scientific Journal Database, VIP and China Biomedical Literature Database (CBM). Clinical randomized controlled trials of four traditional Chinese exercise therapies in the treatment of type 2 diabetes, including Taijiquan, Baduanjin, Yijinjing and Wuqinxi, were retrieved. The search time was conducted from the establishment of the database to 30 October 2022. Two researchers screened the documents that met the inclusion criteria, extracted data according to the preset table and evaluated the methodological quality of the included studies according to the quality evaluation tools recommended by the Cochrane System Reviewer Manual V.5.1. The R language, Stata and ADDIS statistical software programs were used to conduct statistics and analysis of intervention measures. RESULTS: A total of 33 randomized controlled trials with 2609 patients were identified. All patients were from China. The results of the network meta-analysis showed that Taijiquan ranked the best for improving HbA1c, 2-h postprandial blood glucose (2hPG), low-density lipoprotein cholesterol (LDL-C) and insulin sensitivity index indicator levels; Yijinjing reduced fasting plasma glucose (FPG) and total cholesterol (TC) indicator levels for the best probability ranking; Baduanjin improved the triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) probability ranking the most. When the training period was less than 12 weeks, Baduanjin had better effects in improving 2hPG, TC, TG, HDL-C and LDL-C indicator levels. Taijiquan had better effects in reducing FPG levels. When the training period was 12 weeks, the effect of Yijinjing in improving FPG, HbAlc, TC and HDL-C levels was better than that in other traditional Chinese exercise, and Taijiquan had better effects in improving 2hPG, TG and LDL-C indicator levels. When the training period was longer than 12 weeks, Taijiquan had better effects in improving FPG, HbAlc, 2hPG and LDL-C indicator levels, and Baduanjin had better effects in improving TC, TG and HDL-C indicator levels. CONCLUSION: The four traditional Chinese exercise therapies can improve blood glucose levels, blood lipid levels and insulin-related indicators of type 2 diabetes to varying degrees. Studies have shown that Taijiquan has a better targeted treatment effect on type 2 diabetes. SYSTEMATIC REVIEW REGISTRATION: CRD42020214786. PROTOCOL PUBLISHED: We published the protocol article "Network meta-analysis of four kinds of traditional Chinese exercise therapy in the treatment of type 2 diabetes: Protocol for a systematic review" in the BMJ Open magazine 2021, Issue 11, Volume 7.

Nuclear factor-kappa B p50-induced microRNA-20a-3p plays a detrimental role in sepsis-induced acute kidney injury.

Sepsis is the most common cause of acute kidney injury (AKI). Based on microarray-based clustering analysis of miRNAs altered in the kidneys of LPS-AKI mice, miR-20a-3p was upregulated in the kidney tissues of lipopolysaccharide (LPS)-treated mice. We aimed to reveal the functions of miR-20a-3p in septic AKI by establishing the LPS-stimulated mouse model of AKI and constructing the LPS-stimulated HK-2 cells. Reverse transcription-quantitative PCR was used to quantify miR-20a-3p expression and inflammation-associated factors including MCP-1, TNF-α, and IL-6. Silencing of miR-20a-3p reduced inflammation and apoptosis in kidneys as well as alleviated AKI symptoms in mice. The LPS-induced inflammatory response and apoptosis in HK-2 cells were rescued by miR-20a-3p silence. Moreover, nuclear factor-kappa B (NF-κB) is a transcriptional factor for miR-20a-3p to increase its expression. The binding of NF-κB p50 and miR-20a-3p promoter was verified by ChIP assay. To sum up, miR-20a-3p is transcriptionally activated by NF-κB p50, playing a harmful role in sepsis-induced AKI by inducing inflammation and apoptosis.

Using bioinformatics and systems biology methods to identify the mechanism of interaction between COVID-19 and nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is considered a risk factor for severe COVID-19, but the mechanism remains unknown. This study used bioinformatics to help define the relationship between these diseases. The GSE147507 (COVID-19), GSE126848 (NAFLD), and GSE63067 (NAFLD-2) datasets were screened using the Gene Expression Omnibus. Common differentially expressed genes were then identified using a Venn diagram. Gene ontology analysis and KEGG pathway enrichment were performed on the differentially expressed genes. A protein-protein interaction network was also constructed using the STRING platform, and key genes were identified using the Cytoscape plugin. GES63067 was selected for validation of the results. Analysis of ferroptosis gene expression during the development of the 2 diseases and prediction of their upstream miRNAs and lncRNAs. In addition, transcription factors (TFs) and miRNAs related to key genes were identified. Effective drugs that act on target genes were found in the DSigDB. The GSE147507 and GSE126848 datasets were crossed to obtain 28 co-regulated genes, 22 gene ontology terms, 3 KEGG pathways, and 10 key genes. NAFLD may affect COVID-19 progression through immune function and inflammatory signaling pathways. CYBB was predicted to be a differential ferroptosis gene associated with 2 diseases, and the CYBB-hsa-miR-196a/b-5p-TUG1 regulatory axis was identified. TF-gene interactions and TF-miRNA coregulatory network were constructed successfully. A total of 10 drugs, (such as Eckol, sulfinpyrazone, and phenylbutazone) were considered as target drugs for Patients with COVID-19 and NAFLD. This study identified key gene and defined molecular mechanisms associated with the progression of COVID-19 and NAFLD. COVID-19 and NAFLD progression may regulate ferroptosis through the CYBB-hsa-miR-196a/b-5p-TUG1 axis. This study provides additional drug options for the treatment of COVID-19 combined with NAFLD disease.

Octyl gallate targeting the 3C-like protease exhibits highly efficient antiviral activity against swine enteric coronavirus PEDV.

Infection with porcine epidemic diarrhea virus (PEDV) causes severe watery diarrhea in newborn piglets, leading to substantial financial losses for the swine industry. In this study, we screened small molecule drugs targeting 3 C-like protease (3CLpro) by molecular docking, and further evaluated the antiviral activity of the screened drugs against PEDV. Results showed that octyl gallate (OG), a widely used food additive, exhibited strong binding affinity with the 3CLpro active sites of PEDV. Bio-layer interferometry and fluorescence resonance energy transfer revealed that OG directly interacts with PEDV 3CLpro (KD = 549 nM) and inhibits 3CLpro activity (IC50 = 22.15 µM). OG showed a strong inhibition of PEDV replication in vitro. Virus titers were decreased by 0.58 and 0.71 log10 TCID50/mL for the CV777 and HM2017 strains, respectively. In vivo, all piglets in the PEDV-infected group died at 48 h post-infection (hpi), while 75% of piglets in the OG treatment group showed significant relief from the clinical symptoms, pathological damage, and viral loads in the jejunum and ileum. Moreover, the western blotting results showed that OG also has strong antiviral activity against other swine enteric coronaviruses, including transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV). Our findings revealed that OG could be developed as a novel antiviral drug against PEDV. The OG exhibited a potential broad-spectrum antiviral drug for control of other swine enteric coronaviruses.

[Overview and reflection on the development of the first batch of the inheritance studios of acupuncture and moxibustion academic schools].

The development status of the first 11 inheritance studios of acupuncture and moxibustion academic schools is summarized. Aiming at the current problems, it is suggested to establish qualitative and quantitative evaluation standards and establish a fair and reasonable evaluation system, build a systematic scientific theory and excavate the inherent laws of the schools, implement standardized management of the schools and protect the personalized characteristics of the schools, open outpatient clinic of acupuncture and moxibustion schools and promote the characteristic diagnosis and treatment technology, to promote the inheritance and development of acupuncture and moxibustion academic schools.

[Analysis of acupoints selection rules and efficacy evaluation of acupuncture and moxibustion for allergic rhinitis].

OBJECTIVE: To explore the rules of acupoints selection of acupuncture and moxibustion in the treatment of allergic rhinitis (AR) by using data mining technology, as well as to compare the efficacy of different acupoints selection methods. METHODS: Papers about acupuncture and moxibustion for treating AR published from January 2002 to August 2022 was retrieved from Chinese and English databases including CNKI, Wanfang, VIP, SinoMed and PubMed by using keywords of "acupuncture", "moxibustion" and "allergic rhinitis". According to the inclusion and exclusion criteria, the collected literature was screened to establish the AR database. Frequency statistic analysis was conducted for detecting high-frequency acupoints and specific acupoints frequency, and the curative effects of different acupoints selection methods were compared. SPSS26.0 software was used for factor analysis, cluster analysis and QUEST decision tree model identification. RESULTS: A total of 289 papers were included, with 384 acupuncture prescriptions extracted. A total of 99 acupoints were involved with the application frequency of 2 430 times. Among them, the application frequency of Yingxiang (LI20) is the highest (296 times, 12.18%), followed by Yintang (GV24+) and Hegu (LI4), etc. The main invloved meridians are the Bladder Meridian of Foot-Taiyang, the Large Intestine Meridian of Hand-Yangming and the Governor Vessel. The involved specific acupoints with the highest frequency of application is the crossing acupoints. Nine common factors of acupoints combinations units were extracted by factor analysis, and two cluster prescriptions of acupoints combinations correlation were obtained by cluster analysis. Three decision paths of simplified acupoints selection were simulated by the decision tree, with LI20 as the dependent variable. CONCLUSION: In the treatment of AR with acupuncture and moxibustion, the regularities and characteristics of acupoints selection are as follows: 1) often selecting local acupoints and acupoint combinations along meridians, 2) focusing on combination of dispelling pathogenic factors with strengthening vital energy, 3) advocating diversification of acupoint matching methods. The combination of factor analysis, cluster analysis and QUEST decision tree application provides three directions for clinical acupoints selection of AR.

[Brief introduction of Qilu modern acupuncture methods].

Qilu acupuncture and moxibustion has promoted the formation and development of traditional Chinese medicine, which has a special historical position. By systematically collecting, sorting out and summarizing the characteristic acupuncture methods and academic ideas of several Qilu acupuncturists since the founding of the People's Republic of China, the understanding of the advantages and characteristics of Qilu modern acupuncture methods is deepened, aiming to exploring the inheritance and development pattern of Qilu acupuncture methods in the new era.

The reference ranges and characteristics of lymphocyte parameters and the correlation between lymphocyte parameters and routine health indicators in adults from China.

BACKGROUND: Assessment of immune function is of key importance in recognition of disease or healthy status, which still faces challenge in clinical practice. We conducted a 10-center study to investigate lymphocyte parameters including the number, phenotype and IFN-γ-producing ability, and routine laboratory indicators by using the standard method. RESULTS: Although the heterogeneity of lymphocyte parameters was widely found, we have established the normal ranges of these parameters by using pooled data which showed no significant difference among centers. Cluster analysis of 35 parameters found 3 interesting clusters which represented different immunological status. Cluster 1 (parameters: IFN-γ+CD4+ T cell percentage and IFN-γ+CD8+ T cell percentage) represented current lymphocyte function, which was associated with indicators such as body mass index and red blood cell; Cluster 2 (parameters: NK cell number and CD45RA+CD4+ T cell percentage) represented potential of lymphocytes, which was associated with indicators such as albumin and high-density lipoprotein. Cluster 3 (parameters: HLA-DR+CD8+ T cell percentage) represented inflammatory status, which was associated with indicators such as low-density lipoprotein, globulin and age. Correlation analysis found that nutritional indicator albumin is significantly positively correlated with lymphocyte potential. Triglyceride and body mass index were positively correlated with current lymphocyte function rather than lymphocyte potential. The loss of CD8+ T cells was extremely pronounced with increasing age and was one of the most important factors to cause immunosenescence, which may be associated with increased glucose. CONCLUSIONS: We have established the normal ranges of lymphocyte parameters in different areas. This study elucidates the key indicators used to reflect the current function or potential of lymphocytes, which may provide a valuable clue for how to keep immunity healthy.

[Analysis on combination regularities of Houxi (SI3) in ancient times of China based on latent structure model].

OBJECTIVE: To explore the feasibility and application value of combination regularities of acupoint Houxi (SI3) in Chinese ancient times based on latent structure model. METHODS: Relevant articles about SI3 for treating various diseases with acupuncture, moxibustion, acupoint application, etc. were mainly searched from book Chinese Medical Classics (5th edition), followed by establishment of a Database of Houxi Acupoint Recipes. The Lantern 5.0 software was used to construct and analyze the latent structure model of high-frequently-used acupoints. RESULTS: A total of 46 high frequently-used acupoints contained in 240 articles of 26 medical books were collected. The top 7 acupoints are Shenmai (BL62), Hegu (LI4), Qiangu (SI2), Fengchi (GB20), Jianshi (PC5), Wangu (SI4) and Quchi (LI11) in sequence. After modeling the 46 high-frequently used adjunct acupoints, 12 latent variables (Y0-Y11) and 24 latent classes were obtained by setting the cumulative coverage threshold ratio to be 95%. According to the Bayesian information criterion (BIC) measure, the model score was -2 170.68 points. Seven comprehensive clustering models were summarized up according to the latent structure. Compared with the yin meridians, the yang meridians played a more significant role. The multiple combinations of SI3 with specific acupoints provided a reference for clinical practice. The supplementary acupoints mainly distribute in the upper and lower limbs, head, face, neck, etc. and the SI3 acupoint recipes function mainly in dredging and activating meridians and collaterals, clearing away pathologic heat and wind, improving eyesight, and relieving swelling and pain. CONCLUSION: The latent structure model is applicable in analysis of the regularities of SI3 acupoint combination for treating some diseases. Comprehensive clustering is employed to determine the primary acupoint SI3 and adjunct acupoint matching, revealing the common regularity and logical progressive relationship between the primary and secondary points, which may be helpful for teaching, clinical and scientific research.

Effectiveness of acupuncture for multiple sclerosis: A protocol for systematic review and meta-analysis.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease characterized by white matter inflammatory demyelination in the central nervous system (CNS). Its clinical manifestations include decreased vision, diplopia, and limb weakness. As a green and simple traditional Chinese medicine method, acupuncture is gradually recognized by the public. At present, there is still a lack of systematic evaluation on acupuncture treatment of MS. This study aims to evaluate the safety and effectiveness of acupuncture in the treatment of MS, in order to provide a basis for clinical decision-making. METHODS: Randomized controlled trials (RCTs) of acupuncture for MS will be searched in the relevant database, including PubMed, MEDLINE, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure Database (CNKI), WanFang Database, China Biology Medicine Database (CBM), Chinese Scientific Journals Database (VIP), regardless of publication date, or language. All relevant RCTs of electronic searches will be exported to EndNote X9.1 software. Data analysis will be performed using RevMan 5.4 and STATA 14.2 software. RESULTS: Our study aims to explore the efficacy of acupuncture for MS and to provide up-to-date evidence for clinical of MS. We will publish our research results in peer review journals. CONCLUSION: This study will perform a comprehensive systematic review and meta-analysis on the efficacy of acupuncture for MS, making up for the lack of relevant evidence of the clinical use of acupuncture.

[Analysis of clinical indications of acupoint Yinbai (SP1) and its compatible regularities based on data mining technology].

OBJECTIVE: To explore the dominant indications and laws of acupoint compatibility of Yinbai (SP1) by using modern statistics and data mining techniques. METHODS: Literature about indications and acupoint prescriptions of SP1 published before October of 1949 were retrieved from books Chinese Medical Dictionary (5th edition) and Collection of Modern Medical Journals of Traditional Chinese Medicine, and those published from October 1st of 1949 to January of 2021 retrieved from databa-ses of CNKI, Wanfang, VIP, CBM, Web of Science and Pubmed by using key words of Yinbai (SP1),"Guilei"(),"Guiyan"() and Jing (Well)-point of Spleen Meridian, followed by screening the data and establishing a SQL Server database after standardized processing. Then, the descriptive analysis, clustering analysis and association rule analysis were conducted by using Gephi visualization software, SPSS Statistics 25.0 and SPSS Modeler, separately. RESULTS: Before October of 1949, the single SP1 acupoint was usually used to treat 12 types of diseases (mainly the internal diseases as asthma, abdominal distension, vomiting, etc.), and the compound prescriptions of SP1 were usually used to treat 20 types of diseases (mainly the internal diseases as insomnia and dreamful sleep, blood syndrome, etc.), and its adjunct acupoints belong to the first three meridians: the Foot Yangming Stomach Meridian, Foot Taiyang Bladder Meridian and Foot Taiyin Spleen Meridian. After October of 1949, the single SP1 was used to dominantly treat 2 types of diseases (mainly the gynecological diseases as metrorrhagia and metrostaxis, and hypermenorrhea, etc.), and the compound prescriptions of SP1 were frequently used to treat 10 diseases (metrorrhagia and metrostaxis, sequela of apoplexy, mental disorders, insomnia and dreamful sleep, etc.), and the adjunct acupoints of compound prescriptions belong to the first three meridians, namely the Foot Taiyin Spleen Meridian, Concept Vessel and Foot Yangming Stomach Meridian. Before and after October of 1949, the adjunct acupoints with the highest degree of correlation were Lidui (ST45), Shaoshang(LU11), Zusanli(ST36), Sanyinjiao (SP9), and Guanyuan (CV4). Cluster analysis showed that 9 effective clusters obtained may be used as potential prescriptions of SP1, and association rule analysis displayed that the first three strongly connected acupoint matching groups were: SP1-ST45, SP1-LU11, and SP1-ST36 frequently used before October of 1949, and SP1-SP9, SP1-ST36 and SP1-CV4 employed after October of 1949. CONCLUSION: Data mining technology reveals that acupoint SP1 alone is mainly used to treat internal diseases before 1949, and gynecological diseases after 1949; and compound acupoint recipes of SP1 are mainly to treat the internal diseases before 1949, and the gynecological diseases and mental disorders after 1949 in China. The frequently employed adjunct acupoints of SP1 are ST45, LU11, ST36, SP9 and CV4 both before and after 1949.

The effect of acupuncture used for cervical spondylosis of vertebral artery type: A protocol for systematic review and meta-analysis.

BACKGROUND: Cervical spondylosis of vertebral artery type is a common clinical disease. With the change of people's lifestyle and the improvement of people who work at desks, its incidence is also increasing, which can seriously affect people's normal life and work. Acupuncture has been gradually accepted and recognized by the public for its green, simple and safe characteristics. In this systematic review, we aimed to evaluate the effect and safety for patients with cervical spondylosis of vertebral artery type to provide evidence for clinical decision making. METHODS: We will search the following 8 databases from their inception to November 2021: Web of Science, the Cochrane Library, PubMed, Embase, Chinese Biomedicine, China National Knowledge Infrastructure, Chinese Scientific Journals Database, and the WanFang Database. All relevant randomized controlled trials (RCTs) that meet the inclusion criteria will be included in our analysis. Literature screening, data extraction and literature quality assessment will be carried out in a step. Data analysis will be performed using RevMan 5.4 software. RESULTS: Based on the results of this study, we will evaluate the safety and effectiveness of acupuncture in the treatment of vertebral artery type cervical spondylosis. CONCLUSION: This study will provide strong evidence-based medical evidence for acupuncture in treating cervical spondylosis of vertebral artery type. PROSPERO REGISTRATION NUMBER: CRD42021293053.

[Discussion on the theory of he-sea point in Neijing (Inner Canon of Yellow Emperor) and Nanjing (Yellow Emperor's Classic of Eighty-one Difficult Issues )].

By collecting and analyzing the explanation/conception, acupoint name, acupoint location, indications, acupuncture and moxibustion techniques and contraindications of he-sea point recorded in Neijing (Inner Canon of Yellow Emperor) and Nanjing (Yellow Emperor 's Classic of Eighty-one Difficult Issues), it is found that conception of he-sea point of five-shu points has been specifically formed, the names of he-sea points of eleven meridians, the locations and the ways to locate them were recorded. But, the summaries relevant to the indications of the many he-sea points have not been included in teaching materials, thus, it needs to be further analyzed. The acupuncture-moxibustion techniques at he-sea point are flexible and the attention should be paid to distinguish "needling he-sea point in autumn" from "needling he-sea point in winter". Besides, the consideration should be given on coma/fainting induced by arterial bleeding when needling he-sea point, as well as the joint motor impairment caused by over deep insertion in acupuncture.

[Exosomes derived from PMN-MDSCs preconditioned by hypoxia attenuate arthropathy of collagen-induced arthritis mice].

Objective To investigate the role of the exosomes (EX) derived from polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) preconditioned by hypoxia in the treatment of the collagen-induced arthritis (CIA) mouse model. Methods CIA mouse model was induced by bovine type II collagen(Col2) and Freund's adjuvant. PMN-MDSCs were isolated from CIA mouse spleen by magnetic beads. PMN-MDSC-derived exosomes (PMN-MDSC-EXs) were extracted from the supernatant of PMN-MDSCs under normal (210 mL/L O2) and hypoxia (10 mL/L O2) conditions. PMN-MDSC-EXs were identified by transmission electron microscopy and flow cytometry. The surface-specific markers of PMN-MDSC-EXs were detected by Western blotting, including CD9, CD63, heat shock protein 70 (HSP70), and calnexin. PMN-MDSC-EXs were added to the CD4+ T cell proliferation system in vitro to detect immunosuppressive ability. PMN-MDSC-EXs were injected into the CIA mouse model through the tail vein. The clinic scores of joints were recorded every three days, and the joint structures were observed by HE staining. The levels of total IgG, Col2 antibody, interferon γ (IFN-γ), interleukin 17 (IL-17) in the serum were detected by ELISA. The content of miR-29a-3p and miR-93-5p in PMN-MDSC-EXs under normal and hypoxia conditions was detected by real-time quantitative PCR. Results PMN-MDSCs were successfully isolated from the spleens of CIA mice and PMN-MDSC-EXs was prepared under normal and hypoxia conditions. Compared with normal PMN-MDSC-EXs, hypoxia-treated PMN-MDSC-EXs could inhibit the proliferation of CD4+ T cells more effectively. The swelling degree of toes, clinical scores, and joint damage in the group of hypoxia-treated PMN-MDSC-EXs were significantly reduced. The levels of total IgG, Col2 antibody, IFN-γ and IL-17 in the serum decreased after the treatment with hypoxia-treated PMN-MDSC-EXs. The content of miR-29a-3p and miR-93-5p in hypoxia-treated PMN-MDSC-EXs was much higher than that in normal PMN-MDSC-EXs. Conclusion Under hypoxia condition, the immunosuppressive ability of PMN-MDSC-EXs is stronger, which can alleviate the arthropathy of CIA mice more effectively.