Novel insights into macrophage immunometabolism in nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH), an inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), is characterized by liver steatosis, inflammation, hepatocellular injury and different degrees of fibrosis, and has been becoming the leading cause of liver-related morbidity and mortality worldwide. Unfortunately, the pathogenesis of NASH has not been completely clarified, and there are no approved therapeutic drugs. Recent accumulated evidences have revealed the involvement of macrophage in the regulation of host liver steatosis, inflammation and fibrosis, and different phenotypes of macrophages have different metabolic characteristics. Therefore, targeted regulation of macrophage immunometabolism may contribute to the treatment and prognosis of NASH. In this review, we summarized the current evidences of the role of macrophage immunometabolism in NASH, especially focused on the related function conversion, as well as the strategies to promote its polarization balance in the liver, and hold promise for macrophage immunometabolism-targeted therapies in the treatment of NASH.

Herbal Medicine Hewei Jiangni Decoction Is Noninferior to Oral Omeprazole for the Treatment of Nonerosive Gastroesophageal Reflux Disease: A Randomized, Double-Blind, and Double-Dummy Controlled Trail.

Objectives: Conventional approaches for patients with nonerosive gastroesophageal reflux disease (NERD) were not satisfactory. This study aimed to evaluate the effectiveness and mechanisms of Chinese herbal medicine Hewei Jiangni Decoction (HWJND) as a novel and promising regimen for NERD. Methods: A total of 128 patients with NERD were randomly assigned to the Treatment group and Control group. The patients from the Treatment group were administered HWJND (81 g) plus dummy omeprazole (20 mg) daily for 8 weeks, and the others were given dummy HWJND granules (81 g) plus omeprazole (20 mg). The clinical efficacy was assessed using the gastroesophageal reflux disease questionnaire (GERD-Q) scale, patient reported outcomes (PRO) scale, and short form health survey 36 (SF-36) scale at week 4. Moreover, its pharmacological and molecular mechanisms were elucidated based on network pharmacology and molecular docking. Results: Due to case shedding and other reasons, 109 patients, including 56 in the Treatment group and 53 in the Control group completed this study. Our results showed that HWJND significantly improved heartburn, regurgitation, epigastric pain, nausea, and sleep disturbance, which led to a significant reduction of GERD-Q scores in NERD patients. In addition, PRO scores of NERD patients with HWJND administration were improved, and sufficient relief of physical role, body pain, general health, social function, and mental health on the SF-36 scale was also observed in patients after HWJND treatment. We further showed that the curative effect of HWJND was close to that of omeprazole, except for the better improvement of general health and social function. What's more, the main active ingredients of HWJND included quercetin, beta-sitosterol, naringenin, baicalein, and kaempferol were retrieved, and the protective effects of HWJND against NERD may be closely related to targets such as TNF, IL6, IL1B, MMP9, CXCL8, and EGFR, which were mainly enriched in IL-17 signaling pathway and TNF signaling pathway. Conclusion: Our findings demonstrate that HWJND is noninferior to oral omeprazole for the treatment of patients with NERD, plays a therapeutic role through multiple targets and diverse pathways, and holds promise for complementary and alternative therapy for the treatment of NERD. This trial is registered with http://www.chictr.org.cn, Chinese Clinical Trials Registry [ChiCTR2200055960].

Network Pharmacology Analysis of Hewei Jiangni Granule for Gastroesophageal Reflux Disease and Experimental Verification of Its Anti-Neurogenic Inflammation Mechanism.

Purpose: Proton pump inhibitors, as the first-line drugs for treating gastroesophageal reflux disease (GERD), are unable to completely relieve patients' symptoms and patients are prone to recurrence after prolonged drug withdrawal. Thus, it is crucial to find herbal medicines as a complementary and alternative treatment. Hewei Jiangni granule (HWJNG) is a classical Chinese medicinal formula with clinical therapeutic effects on GERD, but its pharmacological mechanism of action remains unclear. This study aimed to explore and then verify the pharmacological mechanisms of HWJNG in GERD therapy. Methods: A network pharmacology approach was applied to explore and then verify the pharmacological mechanisms of HWJNG in GERD therapy. The active ingredients of HWJNG, as well as therapeutic targets of GERD were acquired from specialized databases. The "herb-ingredient-gene-target" network for HWJNG in GERD treatment was built. The protein-protein interaction (PPI) network was constructed to screen the core coincident targets. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. The core targets and signaling pathways associated with the anti-neurogenic inflammatory effect were partially verified via experiments in vivo at molecular level. Results: In total, 179 chemical ingredients in HWJNG and 298 intersection targets between GERD and HWJNG were selected from databases. A large proportion of core targets and top signaling pathways were involved in neurogenic inflammation. HWJNG significantly alleviated pathological injuries of esophagus and reversed dilated intracellular spaces. Additionally, HWJNG markedly inhibited the excessive release of inflammatory cytokines such as interleukin (IL)-1ß, IL-6, tumor necrosis factor receptor (TNF-a), as well as regulated stimulation sensors including transient receptor potential vanilloid type 1 (TRPV1) and its related neuroinflammatory mediators in GERD mice. Conclusion: HWJNG is a promising therapeutic strategy for GERD treatment via regulation of multiple targets and pathways, its effects in alleviating neurogenic inflammation are especially acknowledged.

Chenodeoxycholic Acid Enhances the Effect of Sorafenib in Inhibiting HepG2 Cell Growth Through EGFR/Stat3 Pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly invasive disease with a high mortality rate. Our previous study found that Chenodeoxycholic acid (CDCA) as an endogenous metabolite can enhance the anti-tumor effect. Sorafenib has limited overall efficacy as a first-line agent in HCC, and combined with CDCA may improve its efficacy. METHODS: HepG2 cells and Balb/c nude mice were used respectively for in vitro and in vivo experiments. Flow cytometry, Western blotting, HE and immunohistochemical staining and immunofluorescence were used to study the effects of CDCA combined with sorafenib on HepG2 cell growth and apoptosis-related proteins. Magnetic bead coupling, protein profiling and magnetic bead immunoprecipitation were used to find the targets of CDCA action. The effect of CDCA on EGFR/Stat3 signaling pathway was further verified by knocking down Stat3 and EGFR. Finally, fluorescence confocal, and molecular docking were used to study the binding site of CDCA to EGFR. RESULTS: In this study, we found that CDCA enhanced the effect of sorafenib in inhibiting the proliferation, migration and invasion of HepG2 cells. Magnetic bead immunoprecipitation and protein profiling revealed that CDCA may enhance the effect of sorafenib by affecting the EGFR/Stat3 signaling pathway. Further results from in vitro and in vivo gene knockdown experiments, confocal experiments and molecular docking showed that CDCA enhances the efficacy of sorafenib by binding to the extracellular structural domain of EGFR. CONCLUSION: This study reveals the mechanism that CDCA enhances the inhibitory effect of sorafenib on HepG2 cell growth in vitro and in vivo, providing a potential new combination strategy for the treatment of HCC.

Efficacy and safety of the Chinese herbal formula Hewei Jiangni recipe for NERD with cold-heat complex syndrome: study protocol for a double-blinded randomized controlled trial.

BACKGROUND: Proton pump inhibitor (PPI) is effective for the treatment of nonerosive gastroesophageal reflux (NERD), but long-term use of PPI is prone to have complications and recurrence after withdrawal. Traditional Chinese medicine (TCM) can relieve the symptoms of reflux and improve the quality of life. The purpose of this study is to evaluate the safety and efficacy of Hewei Jiangni recipe (HWJNR) in the treatment of NERD with cold-heat complex syndrome, and clarify the mechanism of HWJNR on NERD based on the correlation analysis of intestinal flora and metabolites. METHODS: This is a single-center, randomized controlled, double-blind, placebo-controlled clinical trial in which 72 eligible participants with NERD and TCM syndrome of intermingled heat and cold will be randomly allocated in the ratio of 1:1 to two groups: TCM group and western medicine group. The TCM group will receive HWJNR with omeprazole enteric-coated tablets placebo, while the western medicine group will receive omeprazole enteric-coated tablets with HWJNR placebo. Each group will be treated for 8 weeks. The primary outcome is the score of gastroesophageal reflux disease (GERD) health-related quality of life questionnaire (GERD-Q). Secondary outcomes include SF-36 quality of life scale (SF-36), patient-reported outcomes (PRO) self-rating scale score, syndrome score of TCM, and adverse events. Mechanistic outcome is the correlation analysis of intestinal flora and metabolites from healthy individuals and NERD participants before and after the treatment respectively. DISCUSSION: The goal of this trial is to investigate the efficacy and safety of HWJNR in the treatment of NERD with cold-heat complex syndrome, and to study the composition structure and metabolite expression profile of intestinal flora in patients with NERD through 16SrRNA sequencing and metabolomic correlation analysis of fecal flora, which makes us identify the dominant links of treatment and reveal the potential mechanism of HWJNR. ChiCTR2000041225 . Registered on 22 December 2020.

Tongxie Anchang Decoction Relieves Visceral Hypersensitivity in Diarrhea-Predominant Irritable Bowel Syndrome Rats by Regulating the NGF/TrkA Signaling Pathway.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disease characterized by visceral hypersensitivity-related abdominal pain, in which diarrhea-predominant IBS (IBS-D) is the main subtype and has a high clinical incidence. Tongxie Anchang Decoction (TXACD) has been proved to significantly improve abdominal pain in patients with IBS-D, but its underlying therapeutic mechanism still remains unclear. In the present study, IBS-D model rats were induced by neonatal maternal separation (NMS) combined with restraint stress (RS). The therapeutic effect of TXACD was evaluated by fecal characteristics and abdominal withdrawal reflex (AWR) scores. After 14 days of intragastric administration, the colonic tissues of rats were collected to detect the protein and gene level of the NGF, TrkA, and TRPV1 using Western blotting and real-time polymerase chain reaction, respectively, and detect mast cells infiltration using toluidine blue staining. The abdominal aorta blood centrifuged was collected for detecting serum levels of SP, 5-HT, and CGRP with ELISA. The results revealed that TXACD could significantly improve visceral hypersensitivity in IBS-D rats, reflected in the decrease of AWR score and the serum levels of SP, 5-HT, and CGRP. In addition, TXACD treatment could alleviate mast cells infiltration. Moreover, the expression levels of the NGF, TrkA, and TRPV1 were repressed by TXACD. The findings of the present study indicated that the therapeutic effect of TXACD on visceral hypersensitivity might be closely related to the downregulation of the NGF/TrkA signaling pathway, the reversal of TRPV1 expression and mast cells infiltration, and the decreased release of neuroendocrine factors SP, 5-HT, and CGRP.

Serum metabolic profiling of traditional Chinese medicine syndromes in patients with diarrhea-predominant irritable bowel syndrome.

OBJECTIVE: The clinical symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D) can be effectively improved by traditional Chinese medicine (TCM) treatment, based on the usage of specific therapies for different TCM syndromes. However, in the stage of diagnosis, the standard criteria for the classification of TCM syndrome were still deficient. Through serum metabolic profiling, this study aimed to explore potential biomarkers in IBS-D patients with different TCM syndromes, which can assist in diagnosis of the disease. METHODS: Serum samples were collected from healthy controls (30 cases), IBS-D patients with Liver-Stagnation and Spleen-Deficiency syndrome (LSSD, 30 cases), Yang Deficiency of Spleen and Kidney syndrome (YDSK, 11 cases) and Damp Abundance due to Spleen-Deficiency syndrome (DASD, 22 cases). Serum metabolic profiling was conducted by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The potential biomarkers were screened by orthogonal partial least square-discriminate analysis, while metabolic pathways undergoing alterations were identified by pathway enrichment analysis in MetaboAnalyst 4.0. RESULTS: Overall, 34 potential biomarkers were identified in LSSD group, 36 in YDSK group and 31 in DASD group. And the 13 metabolites shared by three groups were determined as the potential biomarkers of IBS-D. Glycerophospholipid metabolism was disturbed significantly in IBS-D patients, which may play a role in IBS-D through inflammation. What's more, three TCM syndromes have the specific potential biomarkers in glycerophospholipid metabolism. CONCLUSION: The serum metabolomics revealed that different TCM syndrome types in IBS-D may have different metabolic patterns during disease progression and glycerophospholipid metabolism was one of the pathways, whose metabolism was disturbed differently among three TCM syndromes in IBS-D. Therefore, the specific potential biomarkers in glycerophospholipid metabolism of three TCM syndromes in IBS-D can serve as the objective indicators, which can facilitate the TCM-syndrome objective classification of IBS-D.

Direct Comparison of the Efficacy and Safety of Vonoprazan Versus Proton-Pump Inhibitors for Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common disorder, and is typically treated with proton-pump inhibitors (PPIs) as the recommended first-line therapy. Recently, a new potassium-competitive acid blocker, vonoprazan, was launched in Japan. It is uncertain whether the standard dose of vonoprazan 20 mg is superior to that of PPIs for GERD, so a direct comparison of the therapeutic effects and adverse events between vonoprazan 20 mg and PPIs is needed. METHODS: MEDLINE, the Cochrane Central Register of Controlled Trials, and Embase were chosen as the literature sources. Randomized controlled trials for vonoprazan 20 mg and PPIs published in English were searched. Data from studies meeting the eligibility criteria were extracted individually by two researchers and compared to maintain consistency. RESULTS: Fifty-six articles were identified in the databases, and one study was manually searched and added to the analysis, ultimately yielding six eligible studies. For the main analysis, the risk ratios (RR) of efficacy and adverse events between vonoprazan and PPIs were 1.06 (0.99-1.13) and 1.08 (0.96-1.22), respectively. Subgroup analysis for patients with severe esophagitis at baseline showed significantly higher results for vonoprazan than lansoprazole, with an RR of 1.14 (1.06-1.22). CONCLUSIONS: Our findings suggest that vonoprazan is non-inferior to PPIs as therapy for patients with GERD. Subgroup analysis indicates that vonoprazan is more effective than PPIs for patients with severe erosive esophagitis. The safety outcomes for vonoprazan are similar to those for PPIs.

Study on the clinical mechanism of Tong-Xie-An-Chang Decoction in the treatment of diarrheal irritable bowel syndrome based on single-cell sequencing technology.

BACKGROUND: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a kind of functional gastrointestinal disorder with obscure pathogenesis, and exploration about differential gene expression and cell heterogeneity of T lymphocytes in peripheral blood in IBS-D patients still remains unknown. Clinicians tend to use symptomatic treatment, but the efficacy is unstable and symptoms are prone to relapse. Traditional Chinese Medicine (TCM) is used frequently in IBS-D with stable and lower adverse effects. Tong-Xie-An-Chang Decoction (TXACD) has been proven to be effective in the treatment of IBS-D. However, the underlying therapeutic mechanism remains unclear. This trial aims to evaluate the clinical efficacy and safety of TXACD in IBS-D and elucidate the gene-level mechanism of IBS-D and therapeutic targets of TXACD based on single-cell sequencing technology. METHODS/DESIGN: This is a randomized controlled, double-blind, double-simulation clinical trial in which 72 eligible participants with IBS-D and TCM syndrome of liver depression and spleen deficiency will be randomly allocated in the ratio of 1:1 to two groups: the experimental group and the control group. The experimental group receives Tong-Xie-An-Chang Decoction (TXACD) and Pinaverium bromide tablets placebo; the control group receives pinaverium bromide tablets and TXACD placebo. Each group will be treated for 4 weeks. The primary outcome: the rate of IBS-Symptom Severity Score (IBS-SSS). The secondary outcomes: TCM syndrome score, adequate relief and IBS-Quality of Life Questionnaire (IBS-QOL). Mechanistic outcome is the single-cell sequencing profiling of the T lymphocytes in peripheral blood from IBS-D participants before and after the treatment and healthy individuals. DISCUSSION: This trial will prove the efficacy and safety of TXACD with high-quality evidence and provide a comprehensive perspective on the molecular mechanism of IBS-D by single-cell sequencing profiling, which makes us pinpoint specific biomarkers of IBS-D and therapeutic targets of TXACD.

Network Pharmacology Identifies the Mechanisms of Action of Tongxie Anchang Decoction in the Treatment of Irritable Bowel Syndrome with Diarrhea Predominant.

AIM: This study aims to uncover the pharmacological mechanism of Tongxie Anchang Decoction (TXACD), a new and effective traditional Chinese medicine (TCM) prescription, for treating irritable bowel syndrome with diarrhea predominant (IBS-D) using network pharmacology. METHODS: The active compounds and putative targets of TXACD were retrieved from TCMSP database and published literature; related target genes of IBS-D were retrieved from GeneCards; PPI network of the common target hub gene was constructed by STRING. Furthermore, these hub genes were analyzed using gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. RESULTS: A total of 54 active compounds and 639 targets were identified through a database search. The compound-target network was constructed, and the key compounds were screened out according to the degree. By using the PPI and GO and KEGG enrichment analyses, the pharmacological mechanism network of TXACD in the treatment of IBS-D was constructed. CONCLUSIONS: This study revealed the possible mechanisms by which TXACD treatment alleviated IBS-D involvement in the modulation of multiple targets and multiple pathways, including the immune regulation, inflammatory response, and oxidative stress. These findings provide novel insights into the regulatory role of TXACD in the prevention and treatment of IBS-D and hold promise for herb-based complementary and alternative therapy.

Primary duodenal tuberculosis misdiagnosed as tumor by imaging examination: A case report.

BACKGROUND: Primary duodenal tuberculosis is very rare. Due to a lack of specificity for its presenting symptoms, it is easily misdiagnosed clinically. Review of the few case reports and literature on the topic will help to improve the overall understanding of this disease and aid in differential diagnosis to improve patient outcome. CASE SUMMARY: A 71-year-old man with a 30-plus year history of bronchiectasis and bronchitis presented to the Gastroenterology Department of our hospital complaining of intermittent upper abdominal pain. Initial imaging examination revealed a duodenal space-occupying lesion; subsequent upper abdominal contrast-enhanced computed tomography indicated duodenal malignant tumor. Physical and laboratory examinations showed no obvious abnormalities. In order to confirm further the diagnosis, electronic endoscopy was performed and tissue biopsies were taken. Duodenal histopathology showed granuloma and necrosis. In-depth tuberculosis-related examination did not rule out tuberculosis, so we initiated treatment with anti-tuberculosis drugs. At 6 mo after the anti-tuberculosis drug course, there were no signs of new development of primary lesions by upper abdominal computed tomography, and no complications had manifested. CONCLUSION: This case emphasizes the importance of differential diagnosis for gastrointestinal diseases. Duodenal tuberculosis requires a systematic examination and physician awareness.

The effect of Heweijiangni-decoction on esophageal morphology in a rat model of OVA-induced visceral hypersensitivity followed by acid exposure.

Heweijiangni decoction (HWJND) is an effective traditional Chinese medicine prescription in clinical treatment of nonerosive reflux disease (NERD). Esophageal hypersensitivity and acid contribute to the disease. However, the exact underlying mechanism of action remains unclear. In this study, we observed the effect of HWJND on esophageal morphology in a rat model of ovalbumin (OVA)-induced visceral hypersensitivity followed by acid exposure. Esophageal morphology was assessed by measuring the extent of dilated intercellular spaces (DIS), desmosome disruption, and mitochondrial fragmentation. HWJND in low, moderate, and high doses relieved DIS and desmosome disruption in esophageal epithelium compared with model group (P<0.05 for all doses). In addition, HWJND in high dose protected mitochondria from fragmentation (P<0.05). Other findings suggest that DIS and mitochondrial fragmentation are independent events, and that omeprazole protects mitochondria. Overall, HWJND significantly resists esophageal morphology changes in OVA-induced and acid exposure rat model.

Platelet Count to Spleen Diameter Ratio for the Diagnosis of Gastroesophageal Varices in Liver Cirrhosis: A Systematic Review and Meta-Analysis.

Platelet count to spleen diameter ratio (PSR) was studied extensively as a noninvasive method of diagnosis for varices. The present study aimed to systematically assess the performance of PSR in the diagnosis of varices. PubMed, EMBASE, and article references were searched. The summary receiver operating characteristic curves (AUSROCs), sensitivities, specificities, positive and negative likelihood ratio, and diagnostic odds ratio were calculated. The heterogeneity, quality, and publication bias of studies were evaluated. Subgroup and sensitivity analyses were performed. A total of 49 papers were included. The AUSROCs of PSR for any varices and high-risk varices were 0.8719 and 0.8132, respectively. The summary sensitivities of PSR for any varices and high-risk varices were 0.84 and 0.78, respectively. The summary specificities of PSR for any varices and high-risk varices were 0.78 and 0.67, respectively. The AUSROC of PSR for any varices at the threshold of 909 was 0.8867. The AUSROC of PSR for any varices in viral liver cirrhosis was 0.8675. The overall quality of studies was moderate. Significant heterogeneity and publication bias existed in the study. In conclusion, PSR can be used to identify varices in liver cirrhosis. PSR had a high sensitivity in viral liver cirrhosis.

Effects of Panax notoginseng saponins on proliferation and differentiation of rat embryonic cortical neural stem cells.

BACKGROUND: We aimed to study the effect of Panax notoginseng saponins (PNS) on the proliferation, differentiation, self-renewal, and expressions of basic fibroblast growth factor (bFGF) and brain-derived neurotrophic factor (BDNF) in rat embryonic neural stem cells (NSCs). METHODS: Cortical stem cells were isolated from rat embryos on Embryonic Day 17 (E17) and identified by nestin expression. Subsequently, primary culture, subculturing, and single cell cloning were performed on the cells. After the first cell passage (P1), the cells were resuspended and divided into a control group and a treatment group. Control cells were cultured in serum-free basal culture medium with B27 and dulbecco's modified eagle medium (DMEM)/F12. The same medium supplemented with PNS (100 µg/mL) was used to culture cells in the treatment group. Both groups were incubated at 37°C in a 5% CO2 incubator. Immunocytochemistry was performed 4 days after incubation. RESULTS: Primary, P1, and P2 cells in the treatment group formed neurospheres, as did single cell clones of the P1 cells in this group. After being cultured for 4 days, the number of nestin-, proliferating cell nuclear antigen (PCNA)-, Tuj-1-, neurofilament (NF)-, vimentin-, glial fibrillary acidic protein (GFAP)-, bFGF-, and BDNF-positive cells significantly increased in the treatment group in comparison to the control group. All positively stained cells could form clear clusters. CONCLUSION: PNS can promote rat embryonic cortical NSC survival, self-renewal, proliferation, and differentiation through neurotrophic factors by autocrine or paracrine signaling.

Chinese herbs and their active ingredients for activating xue (blood) promote the proliferation and differentiation of neural stem cells and mesenchymal stem cells.

Some Chinese herbs are anti-thrombolysis, and anti-inflammatory, improves brain RNA content, promotes brain protein synthesis, enhances dopamine function, regulates brain hormones, and improves microcirculation in central nervous system that might improve, repair and rehabilitation from the stroke and brain injury. Specific Chinese herbs and their components, such as Acanthopanax, Angelica, could maintain the survival of neural stem cells, and Rhodiola, Ganoderma spore Polygala, Tetramethylpyrazine, Gardenia, Astragaloside and Ginsenoside Rg1 promoted proliferation of neural stem cells, and Rhodiola, Astragaloside promoted differentiation of neural stem cell into neuron and glia in vivo. Astragalus, Safflower, Musk, Baicalin, Geniposide, Ginkgolide B, Cili polysaccharide, Salidroside, Astragaloside, Antler polypeptides, Ginsenoside Rg1, Panax notoginseng saponins promoted proliferation and differentiation of neural stem cells in vitro. Salvia, Astragalus, Ginsenoside Rg1, P. notoginseng saponins, Musk polypeptide, Muscone and Ginkgolide B promoted neural-directed differentiation of MSCs into nerve cells. These findings are encouraging further research into the Chinese herbs for developing drugs in treating patients of stroke and brain injury.

[Treatment of nonalcoholic steatohepatitis by Jianpi Shugan Recipe: a multi-center, randomized, controlled clinical trial].

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine (CM) intervention in the treatment of nonalcoholic steatohepatitis (NASH) from liver enzyme (ALT), imaging (the liver/spleen CT ratio) and syndrome scores, and to establish standard methods for diagnosis and therapeutic efficacy evaluation with characteristics of CM. METHODS: A multi-center, stratified randomized, parallel controlled, blindness-method evaluated, superiority trial was performed. Totally 204 patients were randomly allocated into two groups, 102 patients in the experimental group (treated with CM) and 102 patients in the control group [treated with Western medicine (WM)]. The alanine aminotransferase (ALT), liver/spleen CT ratio, and clinical symptoms were observed in both groups. RESULTS: Of the randomly allocated 204 cases from 4 hospitals, 3 patients were rejected, and 25 were lost. Totally 176 cases con- formed to the plan with complete follow-ups. After 3 months of treatment, syndrome scores and the improvement of partial clinical symptoms (fatigue and sallow complexion) were superior in the experimental group to those in the control group (P < 0.05). After 3 months of follow-up, the syndrome scores and improvement of partial clinical symptoms (fatigue and sallow complexion) were superior in the experimental group to those in the control group (P < 0.05). There was no statistical difference in improving liver enzymes or the liver/spleen CT ratio between the two groups (P > 0.05). There were 4 adverse reactions/adverse events in the two groups in the process of treatment, mainly covering drug-induced liver injury, diarrhea, and epigastric distension. Adverse reactions had nothing to do with CM treatment. CONCLUSIONS: Jianpi Shugan Recipe had obvious efficacy in treatment of NASH. It could remove the liver fat and play a role in anti-inflammation and liver protection. It also could improve the indices of liver enzymes and the liver/spleen CT ratio effectively, which was superior to Polyene Phosphatidylcholine Capsule (PPC) in improving clinical symptoms, especially for such symptoms as fatigue and sallow complexion.

Effects of Panax notoginseng saponins on proliferation and differentiation of rat hippocampal neural stem cells.

We aimed to investigate the effects of Panax notoginseng saponins (PNS) on proliferation, differentiation and self-renewal of rat hippocampal neural stem cells (NSCs) in vitro. Rat hippocampal NSCs were isolated from post-natal day 1 (P1) rats and cultured in a serum-free medium. The neurospheres were identified by the expressions of nestin, class III ß-tublin (Tuj-1) and glial fibrillary acid protein (GFAP). The cells were given PNS and subjected to oxygen glucose deprivation (OGD) as an in vitro model of brain ischemia reperfusion. The proliferation of NSCs was determined by MTT colorimetry, nestin/BrdU immunofluorescent double-labeling and RT-PCR. Differentiation of NSCs was assessed by immunofluorescent double-labeling of nestin/BrdU, nestin/vimentin, and nestin/Tuj-1. The primary cells and the first two passages of cells formed certain amount of neurospheres, the cells derived from a single cell clone also formed neurospheres. Nestin, BrdU, GFAP and Tuj-1-positive cells appeared in those neurospheres. Compared to the control group, PNS significantly promoted NSC proliferation and the expression of nestin/BrdU, and also enhanced Tuj-1, vimentin, and nestin mRNA expressions in hippocampal NSCs. PNS significantly increased area density, optical density and numbers of nestin/BrdU, nestin/vimentin, and nestin/Tuj-1 positive cells following OGD. These results indicate that PNS can promote proliferation and differentiation of hippocampus NCSs in vitro after OGD, suggesting its potential benefits on neurogenesis and neuroregeneration in brain ischemic injury.