Electroacupuncture Alleviates Cerebral Ischemia-reperfusion Injury by Regulating the S1PR2/TLR4/NLRP3 Signaling Pathway via m6A Methylation of lncRNA H19.

Electroacupuncture (EA) treatment plays a protective role in cerebral ischemiareperfusion (CIR) injury. However, the underlying molecular mechanism is still not fully elucidated. METHODS: All rats were randomly divided into five groups: the SHAM group, MCAO group, MCAO+EA (MEA) group, MCAO+METTL3 overexpression+EA (METTL3) group and MCAO+lncRNA H19 overexpression+EA (lncRNA H19) group. The middle cerebral artery occlusion (MCAO) rats were established to mimic CIR injury. The overexpression of lncRNA H19 and METTL3 was induced by stereotactic injection of lentiviruses into the rat lateral ventricles. The rats in the MEA, METTL3, and lncRNA H19 groups were treated with EA therapy on "Renzhong" (DU26) and "Baihui" (DU20) acupoints (3.85/6.25Hz; 1mA). Besides, the neurological deficit scoring, cerebral infarction area, pathological changes in brain tissue, total RNA m6A level, and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 were detected in this experiment. RESULTS: EA improved the neurological deficit scoring, cerebral infarction area, and pathological injury in MCAO rats, while these beneficial effects of EA on CIR injury were attenuated by the overexpression of METTL3 or lncRNA H19. More importantly, EA down-regulated the total RNA m6A level and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 in MCAO rats. Instead, the overexpression of METTL3 or lncRNA H19 was found to reverse the EA-induced down-regulation. CONCLUSION: The findings indicated that EA might down-regulate the S1PR2/TLR4/NLRP3 signaling pathway via m6A methylation of lncRNA H19 to alleviate CIR injury. Our findings provide a new insight into the molecular mechanism of EA on CIR injury.

Traditional Chinese medicine promotes bone regeneration in bone tissue engineering.

Bone tissue engineering (BTE) is a promising method for the repair of difficult-to-heal bone tissue damage by providing three-dimensional structures for cell attachment, proliferation, and differentiation. Traditional Chinese medicine (TCM) has been introduced as an effective global medical program by the World Health Organization, comprising intricate components, and promoting bone regeneration by regulating multiple mechanisms and targets. This study outlines the potential therapeutic capabilities of TCM combined with BTE in bone regeneration. The effective active components promoting bone regeneration can be generally divided into flavonoids, alkaloids, glycosides, terpenoids, and polyphenols, among others. The chemical structures of the monomers, their sources, efficacy, and mechanisms are described. We summarize the use of compounds and medicinal parts of TCM to stimulate bone regeneration. Finally, the limitations and prospects of applying TCM in BTE are introduced, providing a direction for further development of novel and potential TCM.

N-3 polyunsaturated fatty acids block the trimethylamine-N-oxide- ACE2- TMPRSS2 cascade to inhibit the infection of human endothelial progenitor cells by SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is a novel coronavirus that infects many types of cells and causes cytokine storms, excessive inflammation, acute respiratory distress to induce failure of respiratory system and other critical organs. In this study, our results showed that trimethylamine-N-oxide (TMAO), a metabolite generated by gut microbiota, acts as a regulatory mediator to enhance the inerleukin-6 (IL-6) cytokine production and the infection of human endothelial progenitor cells (hEPCs) by SARS-CoV-2. Treatment of N-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) could effectively block the entry of SARS-CoV-2 in hEPCs. The anti-infection effects of N-3 PUFAs were associated with the inactivation of NF-κB signaling pathway, a decreased expression of the entry receptor angiotensin-converting enzyme 2 (ACE2) and downstream transmembrane serine protease 2 in hEPCs upon the stimulation of TMAO. Treatment of DHA and EPA further effectively inhibited TMAO-mediated expression of IL-6 protein, probably through an inactivation of MAPK/p38/JNK signaling cascades and a downregulation of microRNA (miR)-221 in hEPCs. In conclusion, N-3 PUFAs such as DHA and EPA could effectively act as preventive agents to block the infection of SARS-CoV-2 and IL-6 cytokine production in hEPCs upon the stimulation of TMAO.

A gradient-based discriminant analysis method for process quality control of carbonized TCM via Fourier transform near infrared spectroscopy: A case study on carbonized Typhae Pollen.

Carbonized traditional Chinese medicine (TCM) is a kind of distinctive traditional drug which has been widely used in various bleeding syndromes for over two thousand years, and most of them are still in clinical use. Although they share similar processing method: stir-frying, there are no specific quality standards and few quality control researches carried out on carbonized TCM up until now. Carbonized Typhae Pollen (CTP) is a typical carbonized TCM with efficacy of eliminating blood stasis and stanching bleeding. In this study, a novel process quality control model coupled with near infrared spectroscopy was established, called Gradient-based Discriminant Analysis method (GDA). Compared with conventional modeling methods (Convolutional Neural Network, Linear Discriminant Analysis, Standard Normal Variate-LDA), GDA model applied in fiber optic probe acquisition mode exhibited highest test accuracy (0.961), satisfactory correct identification (internal validation, 100%; external validation, 97.1%) and excellent model stability. This method provided a perfect guideline for process quality control of Carbonized TCM as well as ensured their clinical efficacy.

Folinate Supplementation Ameliorates Methotrexate Induced Mitochondrial Formate Depletion In Vitro and In Vivo.

(1) Background: Antifolate methotrexate (MTX) is the most common disease-modifying antirheumatic drug (DMARD) for treating human rheumatoid arthritis (RA). The mitochondrial-produced formate is essential for folate-mediated one carbon (1C) metabolism. The impacts of MTX on formate homeostasis in unknown, and rigorously controlled kinetic studies can greatly help in this regard. (2) Methods: Combining animal model (8-week old female C57BL/6JNarl mice, n = 18), cell models, stable isotopic tracer studies with gas chromatography/mass spectrometry (GC/MS) platforms, we systematically investigated how MTX interferes with the partitioning of mitochondrial and cytosolic formate metabolism. (3) Results: MTX significantly reduced de novo deoxythymidylate (dTMP) and methionine biosyntheses from mitochondrial-derived formate in cells, mouse liver, and bone marrow, supporting our postulation that MTX depletes mitochondrial 1C supply. Furthermore, MTX inhibited formate generation from mitochondria glycine cleavage system (GCS) both in vitro and in vivo. Folinate selectively rescued 1C metabolic pathways in a tissue-, cellular compartment-, and pathway-specific manner: folinate effectively reversed the inhibition of mitochondrial formate-dependent 1C metabolism in mouse bone marrow (dTMP, methionine, and GCS) and cells (dTMP and GCS) but not methionine synthesis in liver/liver-derived cells. Folinate failed to fully recover hepatic mitochondrial-formate utilization for methionine synthesis, suggesting that the efficacy of clinical folinate rescue in MTX therapy on hepatic methionine metabolism is poor. (4) Conclusion: Conducting studies in mouse and cell models, we demonstrate novel findings that MTX specifically depletes mitochondrial 1C supply that can be ameliorated by folinate supplementation except for hepatic transmethylation. These results imply that clinical use of low-dose MTX may particularly impede 1C metabolism via depletion of mitochondrial formate. The MTX induced systematic and tissue-specific formate depletion needs to be addressed more carefully, and the efficacy of folinate with respect to protecting against such depletion deserves to be evaluated in medical practice.

Research Progress of Gypsum Ustum and Application of Calcium-containing Hemostatic Materials / 中国实验方剂学杂志

Mineral medicine is an indispensable part of traditional Chinese medicine and has a long history of application. Among them， mineral-based hemostatics have been widely applied for the treatment of various hemorrhagic diseases with extensive clinical experience and established efficacy. Gypsum Fibrosum （GF）， a commonly used mineral medicine in clinical， can clear away heat， and relieve anxiety and thirst. Gypsum Ustum （GU） is the processed product of GF after calcining at high temperature. It is mainly composed of anhydrous calcium sulfate （CaSO4） with the functions of moisturizing， promoting muscle growth， astringent sores and hemostasis. GU is often used externally to treat ulcer， itching， eczema， water and fire scalds， trauma bleeding， etc. Studies on the mechanism of hemostasis have shown that Ca2+ （coagulation factor Ⅳ） is involved in many key processes of the internal and external coagulation cascades and can prevent bleeding by regulating platelet activation and aggregation， and promoting the production of insoluble fibrin and the ultimate formation of a blood clot. GF and GU both contain Ca2+ which provide an important material basis of hemostatic effect for both compounds， but GU has a significant hemostatic effect， while GF has no hemostatic effect. After processing， the taste and efficacy of the GF have been obviously changed which reflects the characteristics of processing， but the processing mechanism of GU has not been fully clarified. Therefore， based on studies of GF before and after calcining， this paper focused on these aspects including calcining process， crystal form comparison， element content， efficacy comparison， and summarized various aspects of Ca2+ involved in hemostasis. In addition， the hemostatic properties of other calcium-containing mineral medicines and new calcium-containing hemostatic materials such as calcium alginate， mesoporous calcium silicate and nanogel hemostatic materials were also discussed. The paper aimed to provide a reference for elucidating processing mechanism and clinical dialectical use of GU， also to promote development of new calcium-containing hemostatic materials.

Multi-template molecularly imprinted solid phase extraction and its application in the extraction and separation of multi-components from traditional Chinese medicine / 药学学报

Multi-template molecularly imprinted solid phase extraction not only has the advantages of high selectivity, large adsorption capacity, easy preparation, reuse and low environmental pollution, but also can realize the enrichment and separation of many kinds of compounds. It has attracted wide attention in the extraction and separation of traditional Chinese medicine components. This study summarizes the latest development of multi-template molecularly imprinted solid phase extraction. At the same time, based on the classification of active components of traditional Chinese medicine (flavonoids, alkaloids, phenylpropanol, terpenes, etc.), the latest application of multi-template molecular imprinting solid phase extraction in multi-component separation of traditional Chinese medicine was reviewed, with a view to better application of multi-template molecularly imprinted polymer in active multi-component extraction and separation of traditional Chinese medicine and provide reference for the material basic research of the efficacy of traditional Chinese medicine.

Study on Network Pharmacological Analysis and Preliminary Validation to Understand the Mechanisms of Plantaginis Semen in Treatment of Gouty Nephropathy.

Plantaginis Semen (PS) has been used to promote diuresis and clear away dampness. Recent reports have shown that PS can be used to treat gouty nephropathy (GN). However, the action and mechanism of PS have not been well defined in treating GN. The present study aimed to define the molecular mechanisms of PS as a potential therapeutic approach to treat GN. A combination of network pharmacology and validation experiments in GN is used to understand the potential mechanism. Information on pharmaceutically active compounds in PS and gene information related to GN was obtained from public databases. The compound target network and protein-protein interaction network were constructed to study the mechanism of action of PS in the treatment of GN. The mechanism of action of PS in the treatment of GN was analyzed via Gene Ontology (GO) biological process annotation and Kyoto Gene and Genomics Encyclopedia (KEGG) pathway enrichment. Validation experiments were performed to verify the core targets. The GN rat model was prepared by the method of combining yeast and adenine. Hematoxylin-eosin (HE) staining was used to observe the morphology of renal tissue in rats. ELISA was applied to detect TGF-ß1, TNF-α, and IL-1ß levels in renal tissue. The expressions of TGF-ß1, TNF-α, and IL-1ß were determined using immunohistochemistry. Through the results of network pharmacology, we obtained 9 active components, 118 predicted targets, and 149 GN targets from the public database. Based on the protein-protein interaction (PPI), 26 hub genes for interaction with PS treating for GN were screened, including MMP9, TNF, IL1ß, and IL6. The enrichment analysis results showed that the treatment of GN with PS was mainly involved in the TGF-ß1 signaling pathway, MAPK signaling pathway, TNF signaling pathway, NF-κB signaling pathway, and PI3K Akt signaling pathway. Validation experiment results showed that PS could reduce the content of urinary protein and UA and deregulate the expression of TGF-ß1, TNF-α, and IL-1ß in the treatment of GN. The molecular mechanism of PS in the treatment of GN indicated the synergistic features of multicomponent, multitarget, and multipathway of traditional Chinese medicine, which provided an essential scientific basis for further elucidating the mechanism of PS in the treatment of GN.

Docosahexaenoic acid inhibits the proliferation of Kras/TP53 double mutant pancreatic ductal adenocarcinoma cells through modulation of glutathione level and suppression of nucleotide synthesis.

The treatment of cancer cells obtained by blocking cellular metabolism has received a lot of attention recently. Previous studies have demonstrated that Kras mutation-mediated abnormal glucose metabolism would lead to an aberrant cell proliferation in human pancreatic ductal adenocarcinoma (PDAC) cells. Previous literature has suggested that consumption of fish oil is associated with lower risk of pancreatic cancer. In this study, we investigated the anti-cancer effects of docosahexaenoic acid (DHA) in human PDAC cells in vitro and in vivo. Omega-3 polyunsaturated fatty acids (PUFAs) such as DHA and eicosapentaenoic acid (EPA) significantly inhibited the proliferation of human PDAC cells. The actions of DHA were evaluated through an induction of cell cycle arrest at G1 phase and noticed a decreased expression of cyclin A, cyclin E and cyclin B proteins in HPAF-II cells. Moreover, it was found that co-treatment of DHA and gemcitabine (GEM) effectively induced oxidative stress and cell death in HPAF-II cells. Interestingly, DHA leads to an increased oxidative glutathione /reduced glutathione (GSSG/GSH) ratio and induced cell apoptosis in HPAF-II cells. The findings in the study showed that supplementation of GSH or N-Acetyl Cysteine (NAC) could reverse DHA-mediated cell death in HPAF-II cells. Additionally, DHA significantly increased cellular level of cysteine, cellular NADP/NADPH ratio and the expression of cystathionase (CTH) and SLCA11/xCT antiporter proteins in HPAF-II cells. The action of DHA was, in part, associated with the inactivation of STAT3 cascade in HPAF-II cells. Treatment with xCT inhibitors, such as erastin or sulfasalazine (SSZ), inhibited the cell survival ability in DHA-treated HPAF-II cells. DHA also inhibited nucleotide synthesis in HPAF-II cells. It was demonstrated in a mouse-xenograft model that consumption of fish oil significantly inhibited the growth of pancreatic adenocarcinoma and decreased cellular nucleotide level in tumor tissues. Furthermore, fish oil consumption induced an increment of GSSG/GSH ratio, an upregulation of xCT and CTH proteins in tumor tissues. In conclusion, DHA significantly inhibited survival of PDAC cells both in vitro and in vivo through its recently identified novel mode of action, including an increment in the ratio of GSSG/GSH and NADP/NADPH respectively, and promoting reduction in the levels of nucleotide synthesis.

Effects of spore powder of ganoderma lucidum on CaSR and apoptosis-related proteins in hippocampus tissue of epilepsy following dementia: A protocol of systematic review.

BACKGROUND: This study will investigate the effects of Spore Powder of Ganoderma Lucidum (SPGL) on CaSR and apoptosis-related proteins (ARP) in hippocampus tissue of epilepsy following dementia. METHODS: This study will retrieve all potential studies from both electronic databases (Cochrane Library, EMBASE, MEDLINE, CINAHL, AMED, and CNKI) and other literature sources to assess the effects of SPGL on CaSR and ARP in hippocampus tissue of epilepsy following dementia. We will search all literature sources from the inception to the present. All eligible case-control studies will be included in this study. Two authors will independently carry out literature selection, data collection, and study quality evaluation. Any divergence will be resolved by another author through discussion. RevMan 5.3 software will be employed for data analysis. RESULTS: This study will summarize existing evidence to assess the effects of SPGL on CaSR and ARP in hippocampus tissue of epilepsy following dementia. CONCLUSIONS: The findings of this study may provide helpful evidence of SPGL on CaSR and ARP in hippocampus tissue of epilepsy following dementia. SYSTEMATIC REVIEW REGISTRATION: INPLASY202070041.

Effect of grelin on TRX expression in chronic heart failure tissue: A protocol of systematic review and meta-analysis.

BACKGROUND: The aim of this study is to explore the effect of grelin on TRX expression (TRXE) in chronic heart failure tissue (CHFT). METHODS: We will search electronic databases from inception to the March 1, 2020 in MEDLINE, EMBASE, Cochrane Library, CINAHL, PEDro, the Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. We will not apply any limitations to the language and publication status. Any randomized controlled trials (RCTs) that studied the effect of grelin on TRXE in CHFT will be included. Study quality will be checked by Cochrane risk of bias and evidence quality will be appraised by Grading of Recommendations Assessment Development and Evaluation. All extracted data will be analyzed by RevMan 5.3 Software. RESULTS: This study will summarize the present RCTs to assess the effect of grelin on TRXE in CHFT. CONCLUSION: The results of this study will provide conclusive evidence of the effect of grelin on TRXE in CHFT. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040078.

[Display of low hydraulic resistance channels along Conception Vessel by in vivo fluorography in rats].

OBJECTIVE: To display the low hydraulic resistance channel along the running course of the Conception Vessel (CV) by using in vivo fluorography, so as to provide evidence for the existence of meridians of traditional Chinese medicine from the aspect of interstitial fluid channel. METHODS: A total of 24 male SD rats were randomly divided into 3 groups, namely CV-low impedance spots (CV-LIS), CV-low hydraulic resistance points (CV-LHRP) and non-meridian points (NMP) groups (n＝8 in each group). The CV-LIS (the imaged line between the xiphoid process and symphysis pubis), CV-LHRP (lateral and parallel to LIS) and NMP (lateral and parallel to CV-LHRP) were detected by using meridian detector and biofluid resistance meter, respectively. Sodium fluorescein solution (1%) was injected into the spot (A-spot, upper 1/5 of the CV-LIS), and one of the NMP (about 1 cm lateral and parallel to the A-spot, and the mid-point between the Kidney and Stomach meridian running courses) by using a microsyringe for observing the migration trace of sodium fluorescein. RESULTS: After injection of fluorescein, the migration trace of fluorescein appeared along the CV-LIS and CV-LHRP lines, and only local diffusion was found in the NMP group. The migration trace lengths along the CV-LIS and CV-LHRP were significantly longer than that of the NMP group (P<0.01), and the migration width of CV-LIS and CV-LHRP groups was significantly smaller than that of the NMP group (P<0.01). The migration speed of CV-LIS and CV-LHRP groups was significantly higher than that of the NMP group (P<0.01). CONCLUSION: Fluorography is able to be used to display the running course of CV, possibly supporting the existence of meridians from the interstitial fluid channel and providing a new method for visualization of meridians.

Alternative processing technology for the preparation of carbonized Zingiberis Rhizoma by stir-frying with sand.

Context: Carbonized ginger, a type of charry herb, has been used as a hemostatic medicine since ancient times. However, there are some serious problems such as inhomogeneous heating and emitting smoke during processing with traditional stir-frying method.Objective: To investigate the feasibility to obtain carbonized ginger by stir-frying with sand instead of stir-frying method.Materials and methods: Dried-ginger (100 g) was processed by stir-frying for 30 min at 270 ± 10 °C, or by stir-frying with sand (1:10, w/w) for 8 min at 240 ± 5 °C. The HPLC fingerprint was established for two samples. The adsorption capacity and major components including tannins, gingerols, shogaols and gingerone were quantitated by UV and HPLC, respectively. The hemostatic effect by prothrombin time (PT) and activated partial thromboplastin time (APTT) was evaluated in vitro.Results: The similarity of the two samples for HPLC fingerprints was >0.93. The sand-fried samples showed significantly higher adsorption capacity compared with the stir-fried samples (4.915 vs. 4.593 mg/g; p < 0.05) and higher contents of major components (4.698 vs. 3.930 mg/g, 1.352 vs. 1.144 mg/g, 2.419 vs. 2.095 mg/g, 0.666 vs. 0.568 mg/g and 1.083 vs. 0.911 mg/g for tannins, gingerone, 6-shogaol, 8-shogaol and 10-shogaol, respectively; p < 0.05); while no significant differences were seen for 6-gingerol, 8-gingerol and 10-gingerol (p > 0.05). The PT and APTT values were similar between the stir-fried and sand-fried test groups and significantly lower compared to controls (p < 0.05).Conclusions: The carbonizing process by stir-frying with sand is superior to the stir-frying method for carbonized ginger.

Progress in application of bile acid metabolism in traditional Chinese medicine study / 中国中药杂志

Traditional Chinese medicine boasts aunique theoretical system and rich practical experience. However, traditional Chinese medicine has an unclear material basis, vague pharmacological mechanism, and potential toxicity, which is the key factor to hinder its modernization and wide application. Therefore, when the physico-chemical analysis of chemical components of traditional Chinese medicine is insufficient to reflect the characteristics and mechanisms, the multi-target biological system correlation analysis in conformity to the holistic view of the basic theory of traditional Chinese medicine has gradually attracted wide attention. Specifically, bile acids, as an important endogenous metabolite in the body, play an important role in regulating digestion, absorption and metabolism of nutrients, and greatly impact the health. In recent years, a number of studies have been made on the metabolism pathway of bile acids and their important regulatory effects in body metabolism, making bile acids as a significant target of traditional Chinese medicine on the body. In view of this, based on bile acid metabolism, the paper reviewed the biological functions of bile acids in regulating body metabolism and its interaction with intestinal microbiota, providing a basis for exploring the connotation of bile acid metabolism changes under physiological/pathological conditions of the body. The study progress of bile acid metabolism in traditional Chinese medicine efficacy/toxic mechanism is further reviewed, which provides a basis for exploring the efficacy and hepatotoxicity mechanism of traditional Chinese medicine with bile acid as a biomarker, thereby laying a foundation for the clinical safety of traditional Chinese medicine.

Efficacy of fluoxetine for anorexia nervosa caused by chemotherapy in patients with cholangiocarcinoma.

BACKGROUND: Fluoxetine has been reported to treat anorexia nervosa (AN) caused by chemotherapy in patients with cholangiocarcinoma effectively. However, no study systematically investigated its efficacy and safety. Thus, this study will systematically assess its efficacy and safety for AN caused by chemotherapy in patients with cholangiocarcinoma. METHODS: A comprehensive literature search for relevant studies will be conducted from the following databases from inception to the present: MEDILINE, EMBASE, Cochrane Library, Web of Science, PSYCINFO, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All randomized controlled trials on assessing the efficacy and safety of fluoxetine for AN caused by chemotherapy in patients with cholangiocarcinoma will be considered for inclusion in this study. RevMan V.5.3 software will be used for risk of bias assessment and statistical analysis. RESULTS: This study will summarize the latest evidence of fluoxetine for AN caused by chemotherapy in patients with cholangiocarcinoma through assessing outcomes of weight, depression, anxiety, and quality of life. Additionally, any adverse events will also be analyzed. CONCLUSION: The findings of this study will provide most recent evidence of fluoxetine for AN caused by chemotherapy in patients with cholangiocarcinoma. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019131583.

Acupuncture combined Bobath approach for limbs paralysis after hypertensive intracerebral hemorrhage: A protocol for a systematic review.

BACKGROUND: Previous studies have reported that acupuncture combined Bobath approach (BA) can be used to treat limbs paralysis (LP) after hypertensive intracerebral hemorrhage (HICH) effectively. However, no systematic review has explored its effectiveness and safety for LP following HICH. In this systematic review, we aim to assess the effectiveness and safety of acupuncture plus BA for the treatment of LP following HICH. METHODS: The following 7 databases will be searched from their inception to the February 1, 2019: Cochrane Central Register of Controlled Trials, EMBASE, PUBMED, the Cumulative Index to Nursing and Allied Health Literature, the Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure without any language restrictions. The randomized controlled trials (RCTs) of acupuncture plus BA that evaluate the effectiveness and safety for LP after HICH will be included. The methodological quality of all included studies will be assessed by using Cochrane risk of bias tool. Two authors will independently perform study selection, data extraction, and methodological quality evaluation. Any disagreements occurred between 2 authors will be resolved by a third author involved through discussion. Data will be pooled and analyzed by using RevMan 5.3 Software. RESULTS: This review will evaluate the effectiveness and safety of acupuncture combined BA for LP following HICH. The primary outcome is limbs function. The secondary outcomes are muscle strength, muscle tone, and quality of life, as well as the adverse events. CONCLUSION: The results of this study will summarize the latest evidence of acupuncture combined BA for LP following HICH.

Effect of moxibustion at "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) on bone morphology, metabolism and ERα of bone marrow mesenchymal stem cells in the ovariectomized rats / 中国针灸

OBJECTIVE@#To observe the effects of moxibustion at "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) on bone morphology, metabolism and ERα of bone marrow mesenchymal stem cells (MSCs) in the ovariectomized rats and explore the underlying mechanism of moxibustion at Guanyuan (CV 4) and Sanyinjiao (SP 6) on the regulation of bone metabolism.@*METHODS@#A total of 60 SD rats were randomized into a normal group (20 rats) and an ovariectomy group (40 rats). In the normal group, no any treatment was provided. In the ovariectomy group, the classical ovariectomy was adopted to set up the osteoporosis model. In the 13th week after ovariectomy, 10 rats were collected from each of the normal group and the ovariectomy group for model identification. After model identification, the ovariectomy group was subdivided into a model group, an estradiol group and a moxibustion group, 10 rats in each one. In the normal group and the model group, the gavage was provided with 2 mL 0.9% sodium chloride solution, once a day. In the estradiol group, the gavage was provided with 17β-estradiol 100 μg/(kg•d), once a day. In the moxibustion group, moxibustion was applied at "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6), 15 min at each acupoint, once a day. The 6 treatments were as one course, with 1 day of interval, 12 courses were required. After 12-week intervention, the dual-energy X-ray was adopted to determine the bone mineral density (BMD) and bone mineral content of the whole body in living condition. After sacrificed, HE staining was adopted to observe femur structure, the enzyme-linked immunosorbent assay was to determine the absorbance of estradiol (E) and alkaline phosphatase (ALP) in serum and the real-time quantitative PCR method was to determine the mRNA expressions of ERα of MSCs in tibia and femur.@*RESULTS@#Compared with the model group, BMD was increased obviously in the pelvis and spine in the moxibustion group and the estradiol group (0.05). Compared with the model group, the bone trabeculas were stronger and well connected in the moxibustion group, indicated by HE staining. Compared with the model group, the concentrations of E in serum were increased obviously in the estradiol group and the moxibusiton group (both <0.01), and ALP concentrations reduced obviously in the estradiol group and the moxibustion group (both <0.001), the mRNA expressions of ERα in MSCs increased in the estradiol group and the moxibustion group (both <0.001).@*CONCLUSION@#Moxibustion at "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) effectively increases BMD and bone strength in the ovariectomized rats and the mechanism may be related to the improvement of serum E concentration, the decrease of serum ALP concentration and the up-regulation of mRNA expression of ERα in MSCs.

The mechanism study of protecting kidney of Erzhi Pill based on network pharmacology / 药学学报

Based on the concept of network pharmacology, the main nephroprotective components in Erzhi Pill reported in previous studies, were used to predict the targets through the PharmMapper method. Molecular docking was applied to screen for potential targets and biological information annotation databases (DAVID) was used to analyze the molecular function and biological process of the action targets. The Cytoscape software was used to construct the “ingredient-target-pathway” network of Erzhi Pill for renal injury treatment. TTD and GAD database were then applied to screen for the targets of renal disease for building “ingredient-core target” network. We found that 17 major active ingredients of Erzhi Pill regulated 32 targets (including ESR1, ESR2, GCK, MMP3) and affected 6 pathways, such as PI3K-Akt signaling pathway, estrogen signaling pathway and purine metabolism. This study reflected the nature of traditional Chinese medicine as multi-ingredients, multi-targets and multi-pathways, providing new clues for basic science research on the nephroprotective pharmacological mechanism of Erzhi Pill.

Upregulation of IL-6 is involved in moderate hyperthermia induced proliferation and invasion of hepatocellular carcinoma cells.

Increasing evidences suggested that insufficient radiofrequency ablation (RFA) can paradoxically promote tumor invasion and metastatic processes, while the effects of moderate hyperthermia on cancer progression are not well illustrated. Our present study confirmed moderate hyperthermia treatment can promote the proliferation, migration and invasion of hepatocellular carcinoma (HCC) cells, which was evidenced by the results that moderate hyperthermia induced up regulation of proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-2 (MMP-2). Cellular studies indicated that moderate hyperthermia treatment can increase the mRNA and protein expression of IL-6 and IL-10, while not IL-2, IL-4, IL-8, IL-22, VEGF, TGF-ß, or TNF-α, in HCC cells. Silencing of IL-6, while not IL-10, attenuated moderate hyperthermia treatment induced proliferation and cell invasion. Furthermore, our data revealed the inhibition of NF-κB, while not ERK1/2 or PI3K/Akt, abolished moderate hyperthermia treatment induced production of IL-6. Collectively, our data showed that activation of NF-κB/IL-6 is involved in moderate hyperthermia treatment induced progression of HCC cells.

Comparison in executive function in Chinese preterm and full-term infants at eight months.

Executive function (EF) is increasingly recognized as being responsible for adverse developmental outcomes in preterm-born infants. Several perinatal factors may lead to poor EF development in infancy, and the deficits in EF can be identified in infants as young as eight months. A prospective cohort study was designed to study the EF in Chinese preterm infants and examine the relationship between EF in preterm infants and maternal factors during perinatal period. A total of 88 preterm infants and 88 full-term infants were followed from birth to eight months (corrected age). Cup Task and Planning Test was applied to assess the EF of infants, and the Bayley Scale of Infant Development (BSID-III) was used to evaluate cognitive (MDI) and motor abilities (PDI) of infants. In comparison with full-term infants, the preterm infants performed more poorly on all measures of EF including working memory, inhibition to prepotent responses, inhibition to distraction, and planning, and the differences remained after controlling the MDI and PDI. Anemia and selenium deficiency in mothers during pregnancy contributed to the differences in EF performance. However, maternal depression, hypertension, and diabetes during pregnancy were not related to the EF deficits in preterm infants. Future research should focus on the prevention of anemia and selenium deficiency during pregnancy and whether supplementing selenium in mothers during pregnancy can prevent further deterioration and the development of adverse outcomes of their offspring.