Auricular Vagal Nerve Stimulation Inhibited Central Nerve Growth Factor/Tropomyosin Receptor Kinase A/Phospholipase C-Gamma Signaling Pathway in Functional Dyspepsia Model Rats With Gastric Hypersensitivity.

OBJECTIVE: Functional dyspepsia (FD), which has a complicated pathophysiologic process, is a common functional gastrointestinal disease. Gastric hypersensitivity is the key pathophysiological factor in patients with FD with chronic visceral pain. Auricular vagal nerve stimulation (AVNS) has the therapeutic effect of reducing gastric hypersensitivity by regulating the activity of the vagus nerve. However, the potential molecular mechanism is still unclear. Therefore, we investigated the effects of AVNS on the brain-gut axis through the central nerve growth factor (NGF)/ tropomyosin receptor kinase A (TrkA)/phospholipase C-gamma (PLC-γ) signaling pathway in FD model rats with gastric hypersensitivity. MATERIALS AND METHODS: We established the FD model rats with gastric hypersensitivity by means of colon administration of trinitrobenzenesulfonic acid on ten-day-old rat pups, whereas the control rats were given normal saline. AVNS, sham AVNS, K252a (an inhibitor of TrkA, intraperitoneally), and K252a + AVNS were performed on eight-week-old model rats for five consecutive days. The therapeutic effect of AVNS on gastric hypersensitivity was determined by the measurement of abdominal withdrawal reflex response to gastric distention. NGF in gastric fundus and NGF, TrkA, PLC-γ, and transient receptor potential vanilloid 1 (TRPV1) in the nucleus tractus solitaries (NTS) were detected separately by polymerase chain reaction, Western blot, and immunofluorescence tests. RESULTS: It was found that a high level of NGF in gastric fundus and an upregulation of the NGF/TrkA/PLC-γ signaling pathway in NTS were manifested in model rats. Meanwhile, both AVNS treatment and the administration of K252a not only decreased NGF messenger ribonucleic acid (mRNA) and protein expressions in gastric fundus but also reduced the mRNA expressions of NGF, TrkA, PLC-γ, and TRPV1 and inhibited the protein levels and hyperactive phosphorylation of TrkA/PLC-γ in NTS. In addition, the expressions of NGF and TrkA proteins in NTS were decreased significantly after the immunofluorescence assay. The K252a + AVNS treatment exerted a more sensitive effect on regulating the molecular expressions of the signal pathway than did the K252a treatment. CONCLUSION: AVNS can regulate the brain-gut axis effectively through the central NGF/TrkA/PLC-γ signaling pathway in the NTS, which suggests a potential molecular mechanism of AVNS in ameliorating visceral hypersensitivity in FD model rats.

Untargeted metabolomics analysis of serum and follicular fluid samples from women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with well-established metabolic abnormalities. In the present study, untargeted metabolomics technology was applied to analyze the serum and follicular fluid samples from women with polycystic ovary syndrome and healthy controls using 1H nuclear magnetic resonance (NMR). METHODS: Seventy samples for PCOS analysis were collected in hospital of Shandong University of Traditional Chinese Medicine (Jinan, China), NMR was used as analytical technology and multivariate analysis was applied to analyze metabolomics difference in PCOS and healthy controls. RESULTS: Significant metabolic differences were found in both serum and follicular fluid samples with orthogonal partial least-squares discriminant analysis (OPLS-DA). Three discriminated metabolites (1-Methylhistidine, threonine and Citrate) in both serum and follicular fluid were altered in PCOS patients. Abnormal energy metabolism, lipid metabolism and amino acid metabolism were detected in PCOS patients. Furthermore, more significantly changed amino acids were discovered in follicular fluid samples. CONCLUSIONS: Our findings would provide a resource for further investigations on metabolic disturbance in PCOS patients.

Natural Herbal Medicine as a Treatment Strategy for Myocardial Infarction through the Regulation of Angiogenesis.

Methods: We conducted a literature search on the bioactive components of medicinal plants and their effects on angiogenesis after MI. We searched for articles in Web of Science, MEDLINE, PubMed, Scopus, Google Scholar, and China National Knowledge Infrastructure databases before April 2021. Results: In this article, we summarized the mechanisms by which copper ions, microRNA, Akt1, inflammation, oxidative stress, mitochondria, and pericytes are involved in angiogenesis after myocardial infarction. In addition, we reviewed the angiogenic effects of natural herbal medicines such as Salvia miltiorrhiza Bunge Bunge, Carthamus tinctorius L., Pueraria lobata, Astragalus, Panax ginseng C.A. Mey., Panax notoginseng (Burkill) F.H. Chen, Cinnamomum cassia (L.) J. Presl, Rehmannia glutinosa (Gaertn.) DC., Leonurus japonicus Houtt, Scutellaria baicalensis Georgi., and Geum macrophyllum Willd. Conclusions: Some herbs have the effect of promoting angiogenesis. In the future, natural proangiogenic drugs may become candidates for the treatment of cardiovascular diseases.

Astragalus propinquus schischkin and Salvia miltiorrhiza bunge promote angiogenesis to treat myocardial ischemia via Ang-1/Tie-2/FAK pathway.

Astragalus propinquus Schischkin and Salvia miltiorrhiza Bunge (AS) have been clinically used as adjunctive drugs in the treatment of myocardial ischemia (MI). However, the effect and mechanism of AS on MI have yet to be fully recognized. Here, we explored the cardioprotective effect of their combined use, and the mechanism of promoting angiogenesis through pericyte recruitment. Our data revealed that AS reduced MI and protects cardiac function. AS-treated MI mice exhibited reduced ST-segment displacement and repolarization time, increased ejection fraction, and less BNP and NT-proBNP expression. Pathological studies showed that, AS reduced the area of infarcted myocardium and slowed down the progress of cardiac remodelling and fibrosis. In addition, AS increased the content of platelet-derived growth factor receptors ß (PDGFR-ß), platelet endothelial cell adhesion molecule-1 (CD31) and angiogenesis-related proteins including vascular endothelial cadherin (VE-cadherin), Vascular Endothelial Growth Factor (VEGF) and transforming growth factor ß (TGF-ß). Moreover, these botanical drugs upregulated the expression of Angiopoietin-1 (Ang-1), phosphorylated angiopoietin-1 receptor (p-Tie-2), focal adhesion kinase (FAK) and growth factor receptor bound protein 7 (GRB7), indicating that the cardioprotection-related angiogenesis effect was related to pericyte recruitment, which may be through Ang-1/Tie-2/FAK pathway. In summary, AS can treat MI by protecting cardiac function, attenuating cardiac pathological changes, and hindering the progression of heart failure, which is related to angiogenesis after pericyte recruitment. Therefore, AS at a certain dose can be a promising treatment for MI with broad application prospects.

[Effect of Tiaoshen Jianpi acupuncture therapy on gut microbiota and fecal short-chain fatty acids in patients with diarrhea type irritable bowel syndrome].

OBJECTIVE: To observe the clinical therapeutic effect of Tiaoshen Jianpi acupuncture therapy (acupuncture for regulating the mind and strengthening the spleen) on the gut microbiota and the content of fecal short-chain fatty acids (SCFAs) in patients with diarrhea type irritable bowel syndrome (IBS-D). METHODS: A total of 20 patients with IBS-D and 20 healthy subjects were included. The patients with IBS-D were treated with Tiaoshen Jianpi acupuncture therapy at Baihui (GV 20), Yintang (GV 29), Tianshu (ST 25), Shangjuxu (ST 37), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3). The treatment was given once every two days, 3 times weekly, consecutively for 6 weeks. No intervention was provided for the healthy subjects. Before and after treatment, the IBS symptom severity score (IBS-SSS) was observed in the patients. The fecal samples were collected before and after treatment separately in the patients and in the healthy subjects. Using 16S rRNA sequencing technique, the structure and diversity of gut microbiota were analyzed. Using high-performance liquid chromatography, the content of SCFAs was detected. RESULTS: After treatment, the abdominal pain severity score, the abdominal pain days score, the satisfaction in bowel movement score, the life interference score and the total IBS-SSS score were all lower than those before treatment in the patients with IBS-D (P<0.05). Compared with the healthy subjects, Firmicutes was increased (P<0.05), Bacteroidetes and Proteobacteria were decreased (P<0.05), and Shannon index was reduced (P<0.05) and Simpson index was increased in patients with IBS-D before treatment (P<0.05). Compared before treatment, Firmicutes was decreased (P<0.05), Bacteroidetes and Proteobacteria were increased (P<0.05), and Shannon index was increased (P<0.05) and Simpson index was reduced in the patients with IBS-D after treatment (P<0.05). Besides, the content of SCFAs was reduced after treatment (P<0.05). CONCLUSION: Tiaoshen Jianpi acupuncture therapy relieves abdominal pain and diarrhea, which may be related to regulating the structure and diversity of gut microbiota and reducing the content of fecal SCFAs in the patients with IBS-D.

A flexible tripod fluorescent probe for multiple cations detection and its application in living cells.

To the flexible tripod platform tren (tris(2-aminoethyl)amine), a Rhodamine and two naphthalene fluorophores were introduced. The resulting fluorescence probe named TRN was fully characterized and employed in cell imaging. Probe TRN exhibited high selectivity and excellent sensitivity for the simultaneous fluorescence detection of Zn2+/Hg2+/Al3+/Cu2+. The significant changes in the fluorescence color make naked-eye detection possible. Furthermore, fluorescence imaging experiments of Zn2+/Hg2+/Al3+/Cu2+ in living PC3 cells demonstrated its value for practical applications in biological systems.

Electroacupuncture Relieves Irritable Bowel Syndrome by Regulating IL-18 and Gut Microbial Dysbiosis in a Trinitrobenzene Sulfonic Acid-Induced Post-Inflammatory Animal Model.

Post inflammatory irritable bowel syndrome (PI-IBS), a subset of IBS, is characterized by symptoms of visceral pain, bloating, and changed bowel habits that occur post initial episode of intestinal infection. Gut microbial dysbiosis or inflammation plays a key role in the pathogenesis of abdominal hypersensitivity of PI-IBS. Electroacupuncture (EA) stimulation results in an alleviated PI-IBS-associated symptom. This study investigated the effect of EA on IL-18 and gut microbial dysbiosis in one visceral hypersensitive rat models with PI-IBS. A trinitrobenzene sulfonic acid (TNBS)-induced visceral hypersensitivity rat model was developed. EA stimulation was applied to the ST25 and ST36 acupoints. Animals were assessed using abdominal withdrawal reflex (AWR) scores to determine the development of colonic visceral hypersensitivity. The 16S rRNA was used to correlate microbial diversity. IL-18 expression in colon was quantified by quantitative real-time PCR and western blotting. We identified that model rats had an increased visceral hypersensitivity to colorectal distention at different distention pressures compared with the normal group. Sensitivity to colorectal distention decreased after EA stimulation. The composition of the fecal microbiota was different between groups. Specifically, in the model group Empedobacter, Psychrobacter, Enterococcus, Butyricimonas, Vampirovibrio, Kurthia, Intestinimonas, Neisseria, Falsiporphyromonas, Bilophila, Fusobacterium, Alistipes, Veillonella, Flavonifractor, Clostridium XlVa were more abundant affected genera, whereas Lactobacillus was enriched in normal rats. EA stimulation was correlated with significant decrease in the phyla of Fusobacteria. The mRNA and protein levels of IL-18 were higher in the model group. Meanwhile, EA stimulation attenuated this response. In a word, our findings suggest that PI-IBS is associated with significant increase in IL-18 levels as well as an alteration in microbiome diversity. These changes can be reversed with EA treatment. EA stimulation has a positive effect in alleviating symptoms of visceral hypersensitivity and protecting the gastrointestinal tract.

[Professor SHENG Can-ruo's academic thoughts and acupoint selection experience for hot flashes].

Professor SHENG Can-ruo is a well-known national veteran doctor with over 70 years of clinical experience. He has unique academic thoughts and clinical experience for common diseases and some difficult and complicated diseases. This paper mainly introduces professor SHENG 's syndrome-differentiation thought and experience of acupoint selection for hot flashes. It is emphasized that common hot flashes, such as hot flashes and night sweats, are different between yin and yang. While regulating yin and yang, more attention should be paid to ying-wei harmony, which is not only suitable for women's perimenopausal syndrome, but also for a series of clinical diseases caused by refractory drugs such as endocrine therapy after breast cancer surgery. At the same time of acupoint selection based on syndrome differentiation, a more rational prescriptions should be made according to the duration of the disease and the experience acupoints to improve the clinical efficacy.

[Ultrasound and MRI features of malignant fibrous histiocytoma of soft tissue].

OBJECTIVE: To investigate ultrasound and MRI features of malignant fibrous histiocytoma (MFH) of soft tissue. METHODS: Ultrasound, MRI images and pathological data of 12 patients with malignant fibrous histiocytoma in soft tissue confirmed by operation and pathology were analyzed from January 2012 to August 2018, inlcuding 7 males and 5 females, aged from 36 to 69 years old with an average age of 53 years old; the courses of disease ranged from 4 to 49 months with an average of 28 months. Clinical manifestations were soft tissue masses and pain in the affected limbs. Ultrasound, MRI and contrast-enhanced examination were performed before operation. The lesions, morphology, echo/signal characteristics, color flow signals and enhancement features were observed and compared with pathology. RESULTS: In 12 patients with MFH, 9 patients were primary lesions and 3 patients were recurrent lesions after operation. There were 7 cases of bilateral thighs, 2 cases of calves, 1 case of upper arm, 1 case of buttocks and 1 case of posterior peritoneum. The size ranged from 5.1 to 17.1 cm with an average of 8.7 cm. Ultrasound feature showed lobulated or agglomerate, and focused on low echo; 5 cases had capsule and with clear border; 7 cases were unclear boundary with surrounding tissues; and 6 cases with irregular echo-free. The blood flow signals were around the CDFI, and the internal blood flow signals were different. MRI feature showed lobulated, agglomerate or irregular shape, T1WI showed slightly lower signal or equal signal, T2WI showed high signal and DWI signal increased. Six patients manifested mixed signal inside, 7 patients manifested low signal separation inside, 5 patients with false envelope, and 9 patients manifested infiltration and growth with peripheral edema. T1WI showed uneven strengthening after enhancement. Immunohistochemical expression of Vim, CD68 were positive. CONCLUSIONS: The age, location and imaging features of soft tissue MFH are characteristic. The diagnosis of MFH should be considered when irregular mass occurred in soft tissues of limbs at middle-aged and old people. Echo and signal are homogeneous or mixed. Separation, necrosis and cystic degeneration could be seen in the mass. When the blood flow signals are abundant and solid components are obviously enhanced, the diagnosis of MFH should be considered.

Acupuncture for irritable bowel syndrome: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and change of bowel habit without organic disease. A global perspective given by the World Gastroenterology Organization (WGO) points out that IBS can impact the quality of an individual's daily life, cause socioeconomic problems and potentially impair the patient-physician relationship. It remains a problem to treat IBS due to the complicated pathophysiology. Acupuncture is an alternative therapy recommended for IBS. The aim of this study is to investigate the efficacy and safety of acupuncture therapy for patients with IBS. We also want to explore the correlation between IBS-gene subtypes and acupuncture effect. METHODS/DESIGN: A multicenter randomized controlled trial will be performed in seven hospitals. Six hundred participants will be stratified into two strata (IBS-C or IBS-D). Then, patients within each stratum will be divided into an experimental group and a control group randomly. The experimental group is treated with acupuncture while the control group is treated with Western medicine. All the patients will receive a 6-week treatment and a 3-month follow-up. The primary outcome is the IBS-Symptom Severity Score (IBS-SSS), the secondary outcome is the score of the IBS-Quality of Life (IBS-QoL).The correlation between IBS-gene subtypes and acupuncture effect will be detected based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Outcome measures (including primary and secondary outcome measures) are collected at baseline,1 week, 2 weeks, 4 weeks, and 6 weeks of the intervention, and 12 weeks after the intervention. DISCUSSION: This is a multicenter randomized controlled trial for IBS in China. It may clarify the efficacy of acupuncture as an alternative therapy for IBS. This is the first time ever that the potential mechanism of IBS based on genomics has been investigated. TRIAL REGISTRATION: Chinese Clinical Trials Register, ID: ChiCTR-IOR-15006259 . First registered on 14 April 2015.

[Clinical application value of MRI on malignant fibrous histiocytoma in soft tissue].

OBJECTIVE: To investigate imaging manifestation and clinical application of MRI on malignant fibrous histiocytoma (MFH) in soft tissue. METHODS: Imaging and pathological data of 16 patients with malignant fibrous histiocytoma (MFH) in soft tissue confirmed by surgery and pathology were retrospectively analyzed from January 2009 to August 2016. There were 9 males and 7 females, aged from 34 to 67 years old with an average of 52 years. The courses of disease ranged from 5 to 48 months with an average of 27 months.The main clinical manifestations were soft tissue mass and local pain. All patients were underwent plain and enhanced MRI before operation. Pathogenic sites, MRI manifestation and pathology results were observed after operation. RESULTS: MRI in 16 cases of T1WI showde slightly lower signal or equal signals, of which 6 cases of tumor see mixed signal; in T2WI were high signal, of which 7 cases of internal tumor can be seen low signal separation, 5 cases of turor can be seen flase envelope, 11 cases of tumor with the surrounding boundaries unclear with edema. All lesions showed significantly uneven enhancement. Immunohistochemical examination showed that Vim, CD68 was positive. CONCLUSIONS: Although MRI features of MFH has certain characteristics, the qualitative was more difficult, and ultimately need to determine the pathological and immunohistochemical. But MRI examination has obvious advantages in clarifying range of tumor, invading peripheral blood vessels and nerves, and has important clinical application value for clinical operation plan and postoperative tumor residual and recurrence, and provid reference for clinical curative effect.

[Effects of cotton stalk biochar on microbial community structure and function of continuous cropping cotton rhizosphere soil in Xinjiang, China].

In this study, field trials were conducted to examine the effects of cotton stalk biochar on microbial population, function and structural diversity of microorganisms in rhizosphere soil of continuous cotton cropping field in Xinjiang by plate count, Biolog and DGGE methods. The experiment was a factorial design with four treatments: 1) normal fertilization with cotton stalk removed (NPK); 2) normal fertilization with cotton stalk powdered and returned to field (NPKS); 3) normal fertilization plus cotton stalk biochar at 22.50 t · hm⁻² (NPKB1); and 4) normal fertilization plus cotton stalk biochar at 45.00 t · hm⁻² (NPKB2). The results showed that cotton stalk biochar application obviously increased the numbers of bacteria and actinomycetes in the rhizospheric soil. Compared with NPK treatment, the number of fungi was significantly increased in the NPKB1treatment, but not in the NPKB2 treatment. However, the number of fungi was generally lower in the biochar amended (NPKB1, NPKB2) than in the cotton stalk applied plots (NPKS). Application of cotton stalk biochar increased values of AWCD, and significantly improved microbial richness index, suggesting that the microbial ability of utilizing carbohydrates, amino acids and carboxylic acids, especially phenolic acids was enhanced. The number of DGGE bands of NPKB2 treatment was the greatest, with some species of Gemmatimonadetes, Acidobacteria, Proteobacteria and Actinobacteria being enriched. UPGMC Cluster analysis pointed out that bacterial communities in the rhizospheric soil of NPKB2 treatment were different from those in the NPK, NPKS and NPKB1treatments, which belonged to the same cluster. These results indicated that application of cotton stalk biochar could significantly increase microbial diversity and change soil bacterial community structure in the cotton rhizosphere soil, thus improving the health of soil ecosystem.