Clinical and genetic analysis of a case of Gitelman syndrome accompanied with Graves disease and adrenocortical adenoma: A case report.

RATIONALE: Gitelman syndrome (GS), also known as familial hypokalemia and hypomagnesemia, is a rare autosomal recessive inherited disease caused by primary renal desalinization caused by impaired reabsorption of sodium and chloride ions in the distal renal tubules. We report a case of clinical and genetic characteristics of GS accompanied with Graves disease and adrenocorticotrophic hormone (ACTH)-independent adrenocortical adenoma. PATIENT CONCERNS: The patient is a 45 year old female, was admitted to our hospital, due to a left adrenal gland occupying lesion as the chief complaint. DIAGNOSIS: The patient was finally diagnosed as GS with Graves disease and adrenocortical adenoma. INTERVENTIONS: Potassium magnesium aspartate (1788 mg/d, taken orally 3 times a day (supplement a few times a day, intake method, treatment duration). Contains 217.2 mg of potassium and 70.8 mg of magnesium, and potassium chloride (4.5 g/d, taken orally 3 times a day (supplement a few times a day, intake method, and treatment duration); Potassium 2356 mg), spironolactone (20 mg/d, taken orally once a day (supplement a few times a day, intake method, treatment duration). After 3 months of treatment, the patient's blood potassium fluctuated between 3.3-3.6 mmol/L, and blood magnesium fluctuated between 0.5-0.7 mmol/L, indicating a relief of fatigue symptoms. OUTCOMES: On the day 6 of hospitalization, the symptoms of dizziness, limb fatigue, fatigue and pain were completely relieved on patient. In the follow-up of the following year, no recurrence of the condition was found. LESSONS: The novel c.1444-10(IVS11)G > A variation may be a splicing mutation. The compound heterozygous mutations of the SLC12A3 gene may be the pathogenic cause of this GS pedigree.

[Evidence mapping of Chinese patent medicines in treatment of premature ventricular contractions].

This study employed evidence mapping to systematically sort out the clinical studies about the treatment of premature ventricular contractions with Chinese patent medicines and to reveal the distribution of evidence in this field. The articles about the treatment of premature ventricular contractions with Chinese patent medicines were searched against PubMed, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP with the time interval from January 2016 to December 2022. Evidence was analyzed and presented by charts and graphs combined with text. According to the inclusion and exclusion criteria, 164 papers were included, including 147 interventional studies, 4 observational studies, and 13 systematic reviews. A total of 27 Chinese patent medicines were involved, in which Shensong Yangxin Capsules and Wenxin Granules had high frequency. There were off-label uses in clinical practice. In recent years, the number of articles published in this field showed a decreasing trend. Eight types of outcome indicators were used in interventional studies. Ambulatory electrocardiography, clinical response rate, safety, and echocardiography had high frequency, while the rate of ß-blocker decompensation, major cardiovascular events, and pharmaceutical economic indicators were rarely reported. The evaluation was one-sided. The low quality of the included articles reduced the reliability of the findings. In the future, the clinical use of medicines should be standardized, and the quality of clinical studies should be improved. Comprehensive clinical evaluation should be carried out to provide a sound scientific basis for the treatment of premature ventricular contractions with Chinese patent medicines.

Analysis of the Potential Angiogenic Mechanisms of BuShenHuoXue Decoction against Osteonecrosis of the Femoral Head Based on Network Pharmacology and Experimental Validation.

OBJECTIVE: Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease with a high disability rate. The clinical effect of BuShenHuoXue decoction (BSHX) for ONFH is satisfactory. We aimed to elucidate the potential angiogenic mechanisms of BSHX in a rat femoral osteonecrosis model and bone marrow mesenchymal stem cells (BMSCs). METHODS: With in vivo experiments, we established the steroid-induced osteonecrosis of the femoral head (SONFH) model using Sprague-Dawley (SD) rats (8-week-old). The rats were randomly divided into five group of 12 rats each and given the corresponding interventions: control, model (gavaged with 0.9% saline), BSHX low-, medium- and high-dose groups (0.132 3, 0.264 6, and 0.529 2 g/mL BSHX solution by gavage). After 12 weeks, haematoxylin and eosin (H&E) staining was preformed to evaluate rat osteonecrosis. the expression of angiogenic factors (CD31, VEGFA, KDR, VWF) in rat femoral head was detected by immunohistochemistry, qPCR and western blotting. In cell experiment, BMSCs were isolated and cultured in the femoral bone marrow cavity of 4-week-old SD rats. BMSCs were randomly divided into eight groups and intervened with different doses of BSHX-containing serum and glucocorticoids: control group (CG); BSHX low-, medium-, and high-dose groups (CG + 0.661 5, 1.323, and 2.646 g/kg BSHX gavage rat serum); dexamethasone (Dex) group; and Dex + BSHX low-, medium-, and high-dose groups (Dex + 0.661 5, 1.323, and 2.646 g/kg BSHX gavaged rat serum), the effects of BSHX-containing serum on the angiogenic capacity of BMSCs were examined by qPCR and Western blotting. A co-culture system of rat aortic endothelial cells (RAOECs) and BMSCs was then established. Migration and angiogenesis of RAOECs were observed using angiogenesis and transwell assay. Identification of potential targets of BSHX against ONFH was obtained using network pharmacology. RESULTS: BSHX upregulated the expression of CD31, VEGFA, KDR, and VWF in rat femoral head samples and BMSCs (p < 0.05, vs. control group or model group). Different concentrations of BSHX-containing serum significantly ameliorated the inhibition of CD31, VEGFA, KDR and VWF expression by high concentrations of Dex. BSHX-containing serum-induced BMSCs promoted the migration and angiogenesis of RAOECs, reversed to some extent the adverse effect of Dex on microangiogenesis in RAOECs, and increased the number of microangiogenic vessels. Furthermore, we identified VEGFA, COL1A1, COL3A1, and SPP1 as important targets of BSHX against ONFH. CONCLUSION: BSHX upregulated the expression of angiogenic factors in the femoral head tissue of ONFH model rats and promoted the angiogenic capacity of rat RAOECs and BMSCs. This study provides an important basis for the use of BSHX for ONFH prevention and treatment.

Sleep Patterns Modify the Association between Vitamin D Status and Coronary Heart Disease: Results from NHANES 2005-2008.

BACKGROUND: Although an increased risk of coronary heart disease (CHD) has been reported in individuals with low vitamin D status, this remains controversial. Growing evidence suggests that sleep behaviors may influence vitamin D endocrine functions. OBJECTIVES: We explored the association between serum 25-hydroxyvitamin D [[25(OH)D] concentrations and CHD and whether sleep behaviors modify this relationship. METHODS: A cross-sectional analysis of 7511 adults aged ≥20 y in 2005-2008 National Health and Nutrition Examination Survey (NHANES) that included serum 25(OH)D concentrations and provided information on sleep behaviors and history of CHD was performed. Logistic regression models were used to assess the association between serum 25(OH)D concentrations and CHD, whereas stratified analyses and multiplicative interaction tests were used to evaluate the modification effect of overall sleep patterns and each sleep factor on this relationship. The overall sleep patterns integrated 4 sleep behaviors (sleep duration, snoring, insomnia, and daytime sleepiness) in the form of healthy sleep score. RESULTS: Serum 25(OH)D concentrations were inversely associated with risk of CHD (P < 0.01). Hypovitaminosis D [serum 25(OH)D <50nmol/L] was associated with a 71% increased risk of CHD (OR: 1.71; 95% CI: 1.28, 2.28; P < 0.01) compared with that in participants with sufficient vitamin D [serum 25(OH)D ≥75nmol/L], and the association was more evident and stable among participants with poor sleep patterns (P-interaction < 0.01). Among the individual sleep behaviors, sleep duration had the strongest interaction with 25(OH)D (P-interaction < 0.05). The association between serum 25(OH)D concentrations and risk of CHD was more pronounced in participants with sleep duration <7 h/d or >8 h/d compared with those with sleep duration 7-8 h/d. CONCLUSIONS: These findings suggest that the influence of lifestyle-related behavioral risk factors, such as sleep behaviors (especially sleep duration), need to be considered when evaluating the association between serum 25(OH)D concentrations and CHD as well as the clinical benefits of vitamin D supplementation.

A Systematic Method for the Identification of Aporphine Alkaloid Constituents in Sabia schumanniana Diels Using UHPLC-Q-Exactive Orbitrap/Mass Spectrometry

Sabia schumanniana Diels (SSD) is a plant whose stems are used in traditional folk medicine for the treatment of lumbago and arthralgia. Previous studies have revealed chemical constituents of SSD, including triterpenoids and aporphine alkaloids. Aporphine alkaloids contain a variety of active components, which might facilitate the effective treatment of lumbago and arthralgia. However, only 5-oxoaporphine (fuseine) has been discovered in SSD to date. In this study, we sought to systematically identify the aporphine alkaloids in SSD. We established a fast and reliable method for the detection and identification of these aporphine alkaloids based on ultra-high-performance liquid chromatography (UHPLC)-Q-Exactive-Orbitrap/mass spectrometry combined with parallel reaction monitoring (PRM). We separated all of the analyzed samples using a Thermo Scientific Hypersil GOLD™ aQ C18 column (100 mm × 2.1 mm, 1.9 µm). Finally, we identified a total of 70 compounds by using data such as retention times and diagnostic ions. No fewer than 69 of these SSD aporphine alkaloids have been reported here for the first time. These findings may assist in future studies concerning this plant and will ultimately contribute to the research and development of new drugs.

Network pharmacological analysis of active components of Xiaoliu decoction in the treatment of glioblastoma multiforme.

Background: Glioblastoma multiforme (GBM) is the most aggressive primary nervous system brain tumor. There is still a lack of effective methods to control its progression and recurrence in clinical treatment. It is clinically found that Xiaoliu Decoction (XLD) has the effect of treating brain tumors and preventing tumor recurrence. However, its mechanism is still unclear. Methods: Search the Traditional Chinese Medicine System Pharmacology Database (TCSMP) for efficient substances for the treatment of XLD in the treatment of GBM, and target the targeted genes of the effective ingredients to construct a network. At the same time, download GBM-related gene expression data from the TCGA and GTEX databases, screen differential expression bases, and establish a drug target disease network. Through bioinformatics analysis, the target genes and shared genes of the selected Chinese medicines are analyzed. Finally, molecular docking was performed to further clarify the possibility of XLD in multiple GBMs. Results: We screened 894 differentially expressed genes in GBM, 230 XLD active ingredients and 169 predicted targets of its active compounds, of which 19 target genes are related to the differential expression of GBM. Bioinformatics analysis shows that these targets are closely related to cell proliferation, cell cycle regulation, and DNA synthesis. Finally, through molecular docking, it was further confirmed that Tanshinone IIA, the active ingredient of XLD, was tightly bound to key proteins. Conclusion: To sum up, the results of this study suggest that the mechanism of XLD in the treatment of GBM involves multiple targets and signal pathways related to tumorigenesis and development. This study not only provides a new theoretical basis for the treatment of glioblastoma multiforme with traditional Chinese medicine, but also provides a new idea for the research and development of targeted drugs for the treatment of glioblastoma multiforme.

Schisantherin D from Schisandra chinensis (Turcz.) Baill. exhibits anti-liver fibrosis capacity via modulating ETBR involved signaling, an in vitro and in vivo study.

Excess levels of chemical hepatotoxicants (alcohol, aflatoxin B1), oxidative drugs (acetaminophen) and some cytokines (ET-1, TGF-ß1) can induce chronic or acute liver injury. After these, the severe hepatic disease, especially the liver fibrosis (LF) occurs without taking measures, which brings threat to human health. The dibenzocyclooctadiene lignans of S. chinensis (SCDLs) were found to act as the hepatoprotective components via blocking endothelin B receptor (ETBR). While study on its anti-LF mechanisms especially for its refined compound of schisantherin D (SC-D) is still a lack. So this study aims to investigate the anti-fibrosis effect of SC-D with in vitro and in vivo assays. Bioinformatics analysis revealed the close relations of ETBR to Smad2, Smad3, Nrf2, etc. in LF-related signaling pathways (such as TGF-ß/Smad and Nrf2/ARE). Histopathological staining on livers showed the recovery trend in SC-D treated LF mice. SC-D also modulated expressions of ETBR and fibrosis or anti-oxidative related proteins (such as TIMP1, p-Smad2/3, Nrf2, Smad7, etc.) in LF mice livers. Serum levels of TNF-α, COLI, ALT, AST and LDH in SC-D treated mice were also downregulated compared with LF mice, and upregulated expression of GSH. In vitro studies, SC-D also modulated expressions of LF-related proteins to the normal tendency in LX-2 cell, while weakened its anti- LX-2 proliferation effect by transfections of si-Smad7 or si-Nrf2. Accordingly the anti-LF approach of SC-D showed relations with modulating ETBR linked fibrosis and anti-oxidative related signaling. Also, Smad7 and Nrf2 might be the key factors for SC-D mediated anti-LF effect.

Effect of astragaloside IV and salvianolic acid B on antioxidant stress and vascular endothelial protection in the treatment of atherosclerosis based on metabonomics.

Vascular endothelial cells and oxidation reduction system play an important role in the pathogenesis of atherosclerosis (AS). If these conditions are disordered, it will inevitably lead to plaque formation and even rupture. Astragaloside IV (AsIV) and salvianolic acid B (Sal B) are the main active ingredients of Astragalus membranaceus and Salvia miltiorrhiza, respectively, and found to ameliorate vascular endothelial dysfunction and protect against oxidative stress in recent studies. However, it is still unknown if the combination of AsIV and Sal B (AsIV + Sal B) can inhibit the development of plaque through amplifying the protective effect of vascular endothelial cells and anti-oxidative stress effect. To clarify the role of AsIV + Sal B in AS, we observed the efficacy of each group (Control, Model, AsIV, Sal B, and AsIV + Sal B) by biomolecular assays, such as observing the pathological morphology of the aorta by oil red O staining, evaluating the level of oxidative stress and endothelial cells in the serum by the Elisa test, and analyzing the changes of all small molecule metabolites in liver tissue by UPLC-QTOF-MS. Results showed that AsIV, Sal B and AsIV + Sal B decreased the deposition of lipid in the arterial wall, so as to exert the effect of anti-oxidant stress and vascular endothelial protection, where the inhibitory effect of AsIV + Sal B was the most obvious. Metabonomics analysis showed that Sal B regulated the metabolic pathways of arginine and proline. AsIV regulated glycerol metabolism and saturated fatty acid biosynthesis metabolism. AsIV + Sal B is mainly related to the regulation of the citrate cycle (TCA cycle), alanine, aspartic acid, and glutamate metabolism, cysteine, and methionine metabolism. Succinic acid and methionine are synergistic metabolites that exert an enhancing effect when AsIV and Sal B were used in combination. In conclusion, we demonstrated that AsIV acompanied with Sal B can be successfully used for anti-oxidative stress and vascular endothelial protection of AS, and succinic acid and methionine are the synergistic metabolites.

Network pharmacological analysis of active components of Tongqiao Huoxue Decoction in the treatment of intracerebral hemorrhage.

Background: Intracerebral hemorrhage (ICH) is a type of stroke which results in a high disability and mortality rate and has a poor prognosis. Tongqiao Huoxue Decoction (TQHXD) is a classical Chinese prescription. Clinical practice has proven that TQHXD can promote blood circulation and can effectively treat ICH and its sequelae. However, the current mechanism is still unclear. Methods: The chemical components and target genes of TQHXD were collected from the Traditional Chinese medicine (TCM) Systems Pharmacology and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine analysis platforms, and the gene expression data of ICH tissues were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed to obtain differentially co-expressed gene pairs and build a drug-target-disease network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the obtained target genes and shared genes. Finally, molecular docking was carried out to further clarify the utility of TQHXD for the treatment of ICH. Results: A total of 304 differentially expressed genes in ICH, 42 TQHXD active ingredients, and 279 predicted targets of its active compounds were obtained. Bioinformatics analysis showed that they were involved in angiogenesis, the regulation of wound healing, and other biological processes. Furthermore, their participation in fluid shear stress and the atherosclerosis signaling pathway indicated their close association with the pathological processes of ICH. Finally, molecular docking was carried out to further confirm the tightly binding structural sites of the effective components of TQHXD and key proteins. Conclusions: In summary, the results of this study suggest that the mechanism of action of TQHXD in the treatment of ICH involves multiple targets and signaling pathways related to its occurrence and development. This study not only provides a new theoretical basis for the treatment of ICH with traditional Chinese medicine, but also provides new ideas for the research and development of drugs for the treatment of ICH.

[Diterpenoids from Rabdosia flexicaulis].

The genus Rabdosia is famous for the abundance of diverse and novel ent-kaurane diterpenoids. However, only a few ent-kauranoids have been discovered from R. flexicaulis since the investigation on its chemical constituents is not systematic. To find novel bioactive diterpenoids, the ethyl acetate extract of the above ground part of R. flexicaulis in Daofu County, Sichuan Province was obtained by column chromatography. One new compound and five known ones were identified as flexicaulin E(1), forrestin B(2), inf-lexarabdonin D(3), 7α-hydroxydehydroabietic acid(4), 15-hydroxydehydroabietic acid(5), and pomiferin F(6) by spectral techniques. Compounds 1-3 were the ent-kaurane diterpenoids isolated from this species for the first time. Compounds 4-6, aromatic abie-tanoids, were isolated from the genus Rabdosia for the first time.

(Micro) nanoplastics promote the risk of antibiotic resistance gene propagation in biological phosphorus removal system.

Microplastics (MPs), nanoplastics (NPs) and antibiotic resistance genes (ARGs), as emerging pollutants, have been frequently detected in wastewater treatment plants. However, the behavior of phosphorus and ARGs under MP and NP (MP/NP) pressure in biological phosphorus removal (BPR) system is still unknown. This study investigated the effects of MP/NPs on phosphorus removal and ARGs propagation in BPR system. Results showed that MP/NPs had no influence on phosphorus removal, but significantly promoted the amplification of tetracycline resistance genes (TRGs). Moreover, the TRG abundance were more facilitated by MPs than NPs, and the TRGs of efflux pump and enzymatic modification mechanism were mainly enriched. Meanwhile, MP/NPs increased the transmission risk of multiple resistance genes and mobile gene elements (MGEs). Microbial communities demonstrated the main polyphosphate accumulating organisms shifted from Acinetobacter to unclassified_Gammaproteobacteria, which explained why phosphorus removal efficiency was unaffected with MP/NP addition. Correlation analysis revealed there was no significant correlation between ARGs and MGEs (intI1 and intI2), but the abundances of potential hosts of ARGs were significantly increased with MP/NP addition, implying microbial community structure changes rather than gene horizontal transfer was the main factor promoting ARG propagation under MP/NP pressure.

Comparison of enucleation between thulium laser and holmium laser for benign prostatic hyperplasia: A systematic review and meta-analysis.

To compare the clinical efficacy and safety of Thulium laser enucleation of prostate (ThuLEP) and Holmium laser enucleation of prostate (HoLEP). We systematically searched PubMed, Embase, and Cochrane Library databases within a period from the date of database establishment to October 2020. RevMan 5.4. was used for calculation and statistical analyses. 8 studies of 2125 patients were included. ThuLEP provided less hemoglobin decrease (MD: -0.37, 95%CI -0.61 to -0.14, P = 0.002) and shorter length of hospital stay (MD: -0.41, 95%CI -0.72 to -0.10, P = 0.01). During the postoperative follow-ups, statistically significant differences only were found in IPSS (MD: -0.96; 95%CI -1.27 to -0.65; P < 0.00001) at the 3rd month. In conclusion, our study demonstrates that ThuLEP, compared with HoLEP, has better security, faster improvement of symptoms. However, our conclusions still require a larger sample size, multi-center, and longer follow-up randomized controlled trials to verify.

Novel insights into antidepressant mechanism of Kai Xin San formula: Inhibiting NLRP3 inflammasome activation by promoting autophagy.

BACKGROUND: Kai Xin San (KXS) was widely applied for the treatment of depression for thousands of years. However, the underlying antidepressant mechanism of KXS remains not clear. PURPOSE: This study aimed to investigate whether NLRP3 inflammasome and autophagy are involved in inflammation-induced depression and antidepressant mechanism of KXS. METHODS: Wistar rats were exposed to chronic unpredictable mild stress (CUMS) for 6 weeks, and KXS (3, 5, and 10 g/kg/d) was administrated during the last 2 weeks of CUMS procedure. The effects of KXS on depressive-like behaviors, neuroinflammation, NLRP3 inflammasome activation, and autophagy were investigated in CUMS rats. Rat astrocytes were employed to further explore the potential mechanism of KXS in regulating NLRP3 inflammasome and autophagy. Autophagy inhibitor 3-methyladenine (3-MA, 5 mM) was used in vitro to elucidate the role of autophagy in the antidepressant mechanism of KXS. RESULTS: In vivo, KXS improved depressive-like behaviors of CUMS rats in sucrose preference test, open field test and forced swimming test. Moreover, KXS inhibited the neuroinflammation induced by CUMS and promoted autophagy in prefrontal cortex of rats. The results in vitro further validated the anti-inflammatory and proautohapgic effects of KXS. More importantly, autophagy inhibitor 3-MA diminished the inhibitory effect of KXS on NLRP3 inflammasome activation in rat astrocytes. CONCLUSION: KXS ameliorated CUMS-induced depressive behaviors in rats and inhibited the NLRP3 inflammasome-mediated inflammation in vivo and in vitro. These effects might be regulated by KXS-induced autophagy.

Efficacy and safety of Chinese herbal medicine Wen Xin granules for the treatment of unstable angina pectoris with Yang deficiency and blood stasis syndrome: study protocol for a randomized controlled trial.

INTRODUCTION: Unstable angina pectoris (UAP) is the common type of coronary heart disease with the risk of developing into acute myocardial infarction (AMI). Currently, there are still numerous patients suffering from recurrent angina after revascularization or conventional medication due to the microvascular lesions, endothelial dysfunction, chronic inflammation, in-stent restenosis, and other factors. As an important part of China's medical and health care system, traditional Chinese medicine (TCM) has rich clinical experience in the treatment of UAP. According to the theory of TCM, Yang deficiency and blood stasis syndrome is a common type of UAP. Wen Xin decoction, as a type of Chinese herbal medicine, has been used in the clinic for years and shown great efficacy in the treatment of UAP with Yang deficiency and blood stasis syndrome. This study aims to evaluate the efficacy and safety of Wen Xin granular in patients with UAP. METHODS AND ANALYSIS: This is a double-blinded, randomized, placebo-controlled clinical trial. A total of 502 participants will be randomly allocated to the intervention group and the placebo group. Based on conventional medication, the intervention group will be treated with Wen Xin granular and the placebo group will be treated with Wen Xin granular placebo. The primary outcomes are major adverse cardiovascular events (MACE). Assessments will be performed 1 year after the treatment. The secondary outcomes include TCM symptom scale score, Seattle angina questionnaire, and thromboelastography. Assessments will be performed at baseline (before randomization) and 4 and 8 weeks after randomization. DISCUSSION: This trial will provide high-quality data on the benefits and risks of Wen Xin granular in patients with UAP. TRIAL REGISTRATION: ClinicalTrials.gov NCT04661709 . Registered on 30 November 2020.

[Effect of moxibustion on colonic mucosal injury and expression of CGRP positive nerve fibers of distal colonic mucosa in ulcerative colitis mice].

OBJECTIVE: To observe the effect of moxibustion at "Zusanli" (ST 36) on distal, middle and proximal colonic mucosal injury and expression of calcitonin gene-related peptide (CGRP) positive nerve fibers of distal colonic mucosa in ulcerative colitis (UC) mice at different time points. METHODS: A total of 51 C57BL/6N mice were randomized into a 7-day control group (n=8), a 7-day model group (n=7), a 7-day moxibustion group (n=7), a 14-day control group (n=6), a 14-day model group (n=14) and a 14-day moxibustion group (n=9). In the model groups and the moxibustion groups, 2% dextran sulfate sodium (DSS) was given for 7-day free drinking to establish the UC model. Three days into modeling, moxibustion was applied at "Zusanli" (ST 36) in the 7-day moxibustion group and the 14-day moxibustion group, once a day, 10 min a time for 5 days and 12 days respectively. HE staining was used to observe the morphology of colonic tissue, the percentages of distal, middle and proximal colonic mucosal injury were calculated. Immunofluorescence staining was used to detected the expressions of positive nerve fibers of distal, middle and proximal colonic mucosa and CGRP positive nerve fibers of distal colonic mucosa. RESULTS: Mucosal injury can be observed in mice after modeling, displaying epithelial layer disappearance, abnormal crypt structure or crypt disappearance. Compared with the 7-day control group, colon length was shortened (P<0.001), percentages of overall, distal, middle colonic mucosal injury were increased (P<0.001), the expressions of positive nerve fibers of distal, middle and proximal colonic mucosa and CGRP positive nerve fibers of distal colonic mucosa were increased (P<0.001, P<0.05, P<0.01) in the 7-day model group. Compared with the 7-day model group, the expressions of positive nerve fibers of middle and distal colonic mucosa and CGRP positive nerve fibers of distal colonic mucosa were decreased in the 7-day moxibustion group (P<0.05). Compared with the 14-day control group, the colon length was shortened (P<0.01), percentage of overall colonic mucosal injury was increased (P<0.001) in the 14-day model group. Compared with the 14-day model group, colon length was lengthened (P<0.05), percentage of overall colonic mucosal injury was decreased (P<0.05) in the 14-day moxibustion group. CONCLUSION: Moxibustion at "Zusanli" (ST 36) can reduce the expressions of positive nerve fibers of colonic mucosa and CGRP positive nerve fibers of distal colonic mucosa, thus, improve the colonic mucosal injury.

Antidepressant effect of electroacupuncture on modulating the expression of c-Fos/AP-1 through the JNK signaling pathway.

The effectiveness and safety of electroacupuncture (EA) for depression have been identified by abundant clinical trials and experimental findings. The c-Jun-NH(2)-terminal kinase (JNK) signaling pathway is considered to be involved in the antidepressant mechanism of EA. However, the antidepressant effect of EA via modulating the expression of c-Fos/activator protein-1 (AP-1) under the condition of JNK inhibition remains unexplored. In this study, we investigated the antidepressant effect and possible mechanism of EA in regulating the expression of c-Fos/AP-1 under the condition of JNK inhibition by SP600125 in rats exposed to chronic unpredictable mild stress (CUMS). The depression-like behaviors were evaluated by the body weight, sucrose preference test (SPT), and open field test (OFT). The expression levels of c-Jun in the hypothalamus, c-Fos in the pituitary gland, and c-Fos and AP-1 in the serum of CUMS induced rat model of depression were detected by ELISA. The results indicated that treatment with EA and fluoxetine can reverse the CUMS-induced depression-like behaviors in rats and can up-regulate the expression levels of c-Jun in the hypothalamus, c-Fos in the pituitary gland, and c-Fos and AP-1 in the serum. Of note, the data demonstrated that SP600125, the inhibitor of JNK signaling pathway, can exert synergistic effect with EA in regulating CUMS-induced abnormal activation of the JNK signaling pathway. The antidepressant effect of EA might be mediated by modulating the expression of c-Fos/AP-1.

Khayalactone- and phragmalin-type limonoids with PTP1B inhibitory activity from Trichilia sinensis Bentv.

An investigation on the extract from the plant Trichilia sinensis Bentv. led to the isolation of 13 new limonoids (1-13), in which two were of khayalactone skeleton and 11 were phragmalin-type limonoids, and eight known phragmalin-type limonoids (14-21). Their structures were elucidated by using spectroscopic techniques and HRESIMS experiment. Compounds 6 and 17 displayed potent protein tyrosine phosphatase 1B inhibitory activity with IC50 values of 1.2 ± 0.1 and 8.1 ± 0.5 µM, respectively.

Xi Lei San Attenuates Dextran Sulfate Sodium-Induced Colitis in Rats and TNF-α-Stimulated Colitis in CACO2 Cells: Involvement of the NLRP3 Inflammasome and Autophagy.

OBJECTIVE: Inflammatory bowel disease (IBD) is a chronic nonspecific inflammatory bowel disease with an unclear etiology. The active ingredients of traditional Chinese medicines (TCMs) exert anti-inflammatory, antitumor, and immunomodulatory effects, and their multitarget characteristics provide them with a unique advantage for treating IBD. However, the therapeutic effects and underlying mechanisms of Xi Lei San in treatment of IBD remain unknown. This study was designed to investigate whether Xi Lei San exerted an anti-inflammatory effect in IBD via a mechanism involving NLRP3 inflammasomes and autophagy. METHODS: We successfully established a rat model of dextran sulfate sodium- (DSS-) induced colitis as well as a cellular model of TNF-α-induced colitis. Xi Lei San and indirubin were identified by HPLC analysis. Rats were treated with Xi Lei San or alum crystals, and their body weights and morphology of intestinal tissues were examined. A western blot analysis was performed to determine the expression levels of inflammasome-related proteins and autophagy-related proteins, ELISA was performed to analyze IL-1ß, IL-18, and IL-33 concentrations, and flow cytometry was used to monitor cell apoptosis and ROS levels. RESULTS: Xi Lei San and indirubin were identified by HPLC analysis. We found that Xi Lei San could significantly increase the weights of rats and improve the structure of the intestinal tissues in DSS-induced colitis model rats. We also found that Xi Lei San significantly inhibited NLRP3 inflammasome activity, reduced the levels of inflammatory cytokines, and suppressed autophagy in DSS-induced colitis model rats. In vitro experiments revealed that Xi Lei San could repress apoptosis as well as ROS and inflammatory cytokine production in TNF-α-induced CACO2 cells by reducing the activity of NLRP3 inflammasomes and autophagy. CONCLUSIONS: Our findings showed that Xi Lei San significantly ameliorated IBD by inhibiting NLRP3 inflammasome, autophagy, and oxidative stress.

[Effect of acupuncture on microglia activation in prefrontal cortex of chronic stress-induced depression rats].

OBJECTIVE: To observe the effect of acupuncture on the expression of proinflammatory cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6), microglia marker ion calcium adaptor protein (Iba-1) and triggering receptor expressed on myeloid cells 2 (TREM2) in the prefrontal cortex of chronic stress-induced depression rats, so as to explore its antidepressant mechanism. METHODS: Thirty-two SD rats were randomly divided into normal control, model, acupuncture and fluoxetine groups, with 8 rats in each group. The depression model was established by using chronic mild unpredictable stress methods for 6 weeks. Manual acupuncture stimulation was applied to "Baihui" (GV20) and "Yintang" (GV29) for 10 min before modeling for 6 weeks. Fluoxetine (10 mg/kg, 1 mg/mL) was given to rats of the fluoxetine group by gavage before stress stimulation, once every day for 6 weeks. The open field test was used to evaluate the behavioral changes of rats. The contents of IL-1ß, IL-6 in the prefrontal cortex were determined by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to determine the expression of Iba-1 in the prefrontal cortex. The TREM2 gene expression in the prefrontal cortex was determined by real time fluorescent quantitative polymerase chain reaction (RT-PCR). RESULTS: After modeling, the crossing numbers and rearing times were significantly decreased in the model group relevant to the control group (P<0.05). After the treatment, the crossing numbers were significantly increased in the acupuncture and fluoxetine groups (P<0.05), while the rearing times in the acupuncture group were significantly increased (P<0.05). Compared with the control group, the contents of IL-1ß, IL-6 and the expression of Iba-1 positive cells in the prefrontal cortex were significantly increased in the model group (P<0.05), while the expression of TREM2 gene in the prefrontal cortex was significantly decreased (P<0.05). After the treatment, the increased levels of IL-1ß, IL-6 and Iba-1 positive cells and the decreased TREM2 gene expression were considerably reversed in both acupuncture and fluoxetine groups compared with the model group (P<0.05). CONCLUSION: Acupuncture intervention plays a positive role in anti-depression in rats, which may be related to its effects in inhibiting the activation of microglia, reducing the expression of proinflammatory cytokines, and increasing TREM2 expression in the prefrontal cortex.

[Current status of fertilizer application and utilization efficiency of winter wheat in Anhui Province, China]. / 安徽省冬小麦施肥现状与肥料利用效率.

Winter wheat is an important crop in Anhui Province. Rational use of fertilizers is crucial for the achievement of successful yield. It is urgently needed to reveal the status of fertilizer application and existing problems in winter wheat planting in Anhui for better fertilization. We conducted a survey on 1591 farmers in the main winter wheat producing areas of Anhui Province. The contents of survey included fertilizer type, fertilizer dosage, fertilization method, planting area and yield level. Based on the survey results, we analyzed the current fertilization status of winter wheat growing areas in Anhui Province. Referred to the average wheat yield and fertilizer usage in Anhui, the relationship between wheat yield and fertilizers, including nitrogen (N), phosphorus (P2O5) and potassium (K2O), was evaluated by Cate-Nelson method (cross-over method) to explore the ways to increase yield and fertilizer utilization efficiency of winter wheat. The results showed that the average yield of winter wheat in Anhui Province was 5185 kg·hm-2, and the average application rates of N, P2O and K2O fertilizers were 206, 80 and 78 kg·hm-2, respectively. Compared with wheat following rice, the N, P2O and K2O fertilization rates of dry stubble wheat was higher by 14, 16 and 3 kg·hm-2, respectively. Overall, the average amount of chemical fertilizer in winter wheat cultivation in Anhui Province was rational, but there were still some problems in fertilization methods, nutrient management and fertilizer types. The results of Cate-Nelson method showed that 23.8%, 21.2% and 25.7% (for N, P2O5 and K2O fertilizers respectively) of winter wheat were below the average level that achieved high yield, reaching highest partial productivity of N, P2O5 and K2O fertilizers. There were 26.3%, 19.3% and 22.5% (for N, P2O5 and K2O fertilizers respectively) of winter wheat were below the average use level which did not achieve high yield. There were 26.2%, 29.6% and 25.0% (for N, P2O5 and K2O fertilizers respectively) of winter wheat realized high yield, but the fertilization rate was high and the partial productivity of N, P2O and K2O fertilizers was relatively low. Our results suggest that the yield and efficiency of winter wheat in Anhui Pro-vince should be improved. The percentage of mechanical fertilization in winter wheat was 62.7% for base fertilizer and 10.0% for topdressing fertilizer, respectively. Though nitrogen fertilizer was applied at different stages, the proportion of base fertilizer that accounted for 69.0% of the total should be decreased appropriately. It's a problem that farmers preferred to use chemical fertilizers but not organic substitution.