Historical Review of Acute Pancreatitis Research Over the Last 80 Years.

OBJECTIVES: Research on acute pancreatitis (AP) has been ongoing for a long time. It is necessary to summarize and investigate the history of AP research. METHODS: Publications related to AP research were retrieved from PubMed. Medical Subject Headings (MeSH) terms, countries, journals, and publication dates were analyzed. Co-occurrence analysis was conducted to illustrate the holistic trend in AP research. A dynamic bar graph, heat maps, and line charts were created to illustrate change trends of MeSH terms. RESULTS: In total, 28,222 publications with 8558 MeSH terms were retrieved from 1941 to 2020. Among these, 16,575 publications with 7228 MeSH terms were from 2001 to 2020. The top 10 MeSH terms showed a considerable change from 1941 to 1970 but remained stable since the 1970s. Four clusters obtained from the co-occurrence analysis were "experiments on animals," "diagnosis and treatment," "prognosis and expectation," and "protein and enzyme." From 1941 to 2020, 33 MeSH terms with increasing trends (MH-I) and 15 MeSH terms with decreasing trends (MH-D) were selected to create a heat map (every decade). Meanwhile, 16 MH-I and 41 MH-D were selected to create the heat map from 2001 to 2020 (every 2 years). CONCLUSION: Over the past 80 years, the pathogenesis, treatment, risk management, and experimental model were the main research highlights. Optimal supportive management, minimally invasive treatment, and prediction of prognosis are subjects of interest for clinical practitioners; signal transduction to identify a target for precise treatment is the focus of experimental research in AP.

Alterations in the Gut Microbiota and Metabolomics of Seafarers after a Six-Month Sea Voyage.

Maintaining the health of seafarers is a difficult task during long-term voyages. Little is known about the corresponding changes in the gut microbiome-host interaction. This study recruited 30 seafarers undertaking a 6-month voyage and analyzed their gut microbiota using 16S rRNA gene sequencing. Fecal untargeted metabolomics analysis was performed using liquid chromatography-mass spectrometry. Significant changes in the composition of the gut microbiota and an increased ratio of Firmicutes/Bacteroidetes at the end (day 180) of the 6-month voyage, relative to the start (day 0), were observed. At the genus level, the abundances of Holdemanella and Plesiomonas were significantly increased, while the abundance of Bacteroides was decreased. Predicted microbial functional analysis revealed significant decreases in folate biosynthesis and biotin metabolism. Furthermore, 20 differential metabolites within six differentially enriched human metabolic pathways (including arginine biosynthesis, lysine degradation, phenylalanine metabolism, sphingolipid metabolism, pentose and glucuronate interconversions, and glycine, serine, and threonine metabolism) were identified by comparing the fecal metabolites at day 0 and day 180. Spearman correlation analysis revealed close relationships between the 14 differential microbiota members and the six differential fecal metabolites that might affect specific human metabolic pathways. This study adopted a multi-omics approach and provides potential targets for maintaining the health of seafarers during long-term voyages. These findings are worthy of more in-depth exploration in future studies. IMPORTANCE Maintaining the health of seafarers undertaking long-term voyages is a difficult task. Apart from the alterations in the gut microbiome and fecal metabolites after a long-term voyage, our study also revealed that 20 differential metabolites within six differentially enriched human metabolic pathways are worthy of attention. Moreover, we found close relationships between the 14 differential microbiota members and the six differential fecal metabolites that might impact specific human metabolic pathways. Accordingly, preventative measures, such as adjusting the gut microbiota by decreasing potential pathobionts or increasing potential probiotics as well as offsetting the decrease in B vitamins and beneficial metabolites (e.g., d-glucuronic acid and citrulline) via dietary adjustment or nutritional supplements, might improve the health of seafarers during long-term sea voyages. These findings provide valuable clues about gut microbiome-host interactions and propose potential targets for maintaining the health of seafarers engaged in long-term sea voyages.

Ziyin Bushen Decoction Alleviates Perimenopausal Syndrome in Rats by Enhancing Estradiol Production.

Perimenopausal syndrome (PMS) has a high incidence rate and affects the physical and mental health of middle-aged and elderly women. The blockage of PMS is significant in improving the health of perimenopausal women. Currently, for PMS prevention and treatment, traditional Chinese medicine (TCM) has become an ideal choice because of its safety and effectiveness. This study aimed to explore the anti-PMS effects of Ziyin Bushen Decoction (DKTP) and the underlying mechanism. Thirty female Wistar rats were divided into 5 groups (n = 6): control group, low-dose DKTP group, medium-dose DKTP group, high-dose DKTP group, and nilestriol group. The estradiol (E2) level in rat peripheral blood was analyzed using an E2 Radioimmunoassay Kit, and uterine morphologic changes were examined by hematoxylin-eosin staining. Learning and memory ability of rats was assessed by Morris water maze (MWM) and novel object recognition (NOR) task. E2 synthesis, metabolism, and transport associated estrogen receptor-alpha (ERα), GnRHR, CYP17, CYP11A1, CYP19, 17ßHSD, STS, and SHGB were assessed to explore the E2-promoting mechanism of DKTP during PMS treatment. The loss of learning and memory, the decreased estrous and uterine coefficient, and the presence of histopathological changes suggests a successful establishment of rat PMS model. Following DKTP or nilestriol treatment, the above results were reversed. E2 level in serum, uterine, and ovarian tissues was upregulated upon different concentrations of DKTP treatment, indicating that DKTP promotes the E2 level in a dose-dependent manner. DKTP also increased the expression of ERα, CYP17, CYP11A1, CYP19, 17ßHSD, STS, and SHGB while decreased the GnRHR expression in uterine and ovarian tissues, revealing that these key molecules involved in estrogen synthesis, metabolism, and transport in PMS rats. We confirmed the anti-PMS effect of DKTP through enhancing E2 production. Exploring a novel drug based on improving E2 synthesis, metabolism, and transport may represent a novel strategy for PMS prevention and treatment.

Effect of Shenfu Injection on Porcine Renal Function after Cardiopulmonary Resuscitation.

OBJECTIVE: To comprehensively evaluate the protective effect of Shenfu injection (SFI) on renal ischaemia/reperfusion injury (IRI) after cardiopulmonary resuscitation (CPR) through neutrophil gelatinase-associated lipocalin (NGAL) and to explore effective monitoring of early renal injuries after CPR. METHODS: Thirty healthy minipigs were randomly divided into 3 groups: sham operation (SO) (n = 6), control (n = 12), and SFI (n = 12). The SO group underwent only catheterization, whereas the control and SFI groups were subjected to program-controlled electrical stimulation to establish a cardiac arrest (CA) model due to ventricular fibrillation. After CPR, the return of spontaneous circulation was achieved. Each animal in the SFI group was intravenously injected with SFI after resuscitation. Haemodynamic parameters were monitored at baseline and 2, 6, 12, and 24 hr after CPR. At each time point, venous blood samples were collected for NGAL, creatinine, and ATPase screening. RESULTS: After CA, the MAP, CPP, and CO of the animals in the control and SFI groups decreased significantly. However, at 6 hr after CPR, the MAP, CPP, and CO of the animals in the SFI group began to recover gradually; the differences between the control and SFI groups were significant (P < 0.005). The renal damage immediately after CPR appeared to be significant in the pathological examinations. However, the degree of renal injury in the SFI group improved significantly, and the apoptosis index was also notably reduced. The blood and urine NGAL levels were clearly elevated after CPR. The greatest increase in NGAL was found in the control group, which was significantly different from that of the SFI group (P < 0.001). SFI can significantly increase the ATPase activity of kidney tissues after CPR and improve abnormal caspase-3 protein expression. CONCLUSION: SFI can effectively prevent acute kidney injuries caused by CPR through improving energy metabolism and inhibiting apoptosis.

Impact of Buckwheat Fermented Milk Combined with High-Fat Diet on Rats' Gut Microbiota and Short-Chain Fatty Acids.

The aim of this study was to evaluate the effect of buckwheat fermented milk on intestinal flora and short-chain fatty acids (SCFAs) of rats fed a high-fat diet (HFD). Buckwheat fermented milk was made with Lactobacillus plantarum ST-Ⅲ, Lactobacillus bulgaricus, and Streptococcus thermophilus. Thirty-six males C57BL/6 rats (aged 3 weeks and with 9 to 12 g weight) were subjected to a 2-week adaptive period on a normal diet. After a week of acclimatization, the rats were randomly divided into three groups with 12 rats in each group. The high-fat diet with fermented milk (HFDFM) group received HFD supplemented with fermented milk, and the high-fat diet supplemented with buckwheat fermented milk (HFDBFM) group received HFD plus buckwheat fermented milk. Besides, the gavage dose was 0.4 mL/day. After the feedings, colon levels of cytokines and antioxidant indices of the liver, colon, and duodenum tissues were measured. The composition of intestinal flora of rats and the content of SCFAs were determined by gas chromatography-mass spectrometry and Illumina high-throughput sequencing technology. Supplementation with buckwheat fermented milk significantly inhibited the increases in lipopolysaccharide levels in colon and antioxidant indexes in the HFD-fed rats. In addition, buckwheat fermented milk could significantly enhance Firmicutes and decrease Bacteroidetes compared to HFDFM. In addition, SCFA concentrations in HFDBFM were higher than other groups. In conclusion, buckwheat fermented milk can alleviate the damage of HFD to intestinal flora of rats. It modulates microbiota composition and SCFA concentrations to balance the intestinal environment, which will benefit to rats' intestinal health. PRACTICAL APPLICATION: This study explored the effect of buckwheat fermented milk on the regulation of intestinal microflora and SCFAs in rats fed a high-fat diet. It provides new ideas for the development of buckwheat fermented food.

Regulatory Function of Buckwheat-Resistant Starch Supplementation on Lipid Profile and Gut Microbiota in Mice Fed with a High-Fat Diet.

Buckwheat-resistant starch (BRS) has shown to be a nutrient capable of lowering cholesterol and reducing obesity. In this study, the regulatory effects of tartary buckwheat starch on blood lipid level and gut microbiota (Lactobacillus, Bifidobacterium, Enterococcus, and Escherichia coli) in mice fed with a high-fat diet was investigated. Male C57BL/6 mice were separately fed with a normal diet (CON), a high-fat diet (HFD), and high-fat diet supplemented with buckwheat-resistant starch (HFD+BRS) for 6 weeks. After the feedings, lipid profile, blood glucose, plasma levels of cytokines, short-chain fatty acid content in the colon and intestinal flora of fecal were measured. Furthermore, the antioxidant indices of the liver and duodenum tissues were measured to evaluate the antioxidant capacity of mice. Significantly reduced plasma levels of total cholesterol (TC), triglyceride (TG), glucose, and cytokines were observed in the HFD+BRS group, accompanied by an increased antioxidant capacity in the liver and duodenum. In addition, supplementation with BRS significantly inhibited the increase in plasma lipopolysaccharide, tumor necrosis factor-α, and interleukin-6 levels. Gut microbiota composition was regulated by the supplement of BRS, which promoted the growth of Lactobacillus, Bifidobacterium, and Enterococcus, as well as inhibited the growth of Escherichia coli. In contrast to the HFD group, the content of short-chain fatty acids in mice colon increased in the BRS group. In conclusion, BRS benefited the cholesterol and glucose metabolism, as well as optimized gut microbiota composition in mice fed with a high-fat diet. PRACTICAL APPLICATION: This study identified the beneficial effects of tartary buckwheat-resistant starch on the regulation of blood lipids and intestinal flora in mice fed a high-fat diet. The result of this study will provide a basis for the development of probiotic products supplemented with tartary buckwheat-resistant starch and direction for further research.

Toxicological analysis of roast duck flavor components.

The aim of the study was to investigate toxicity of the synthesized roast duck flavor through animal experiment (mice feeding with the flavor for 35 days), and the major toxic compounds (acrylamide and 3,4-benzopyrene) were detected by high performance liquid chromatography. Compared with the control group, the blood biochemical indexes including protein content, bilirubin content, activity of alkaline phosphatase, activity of aspartate transaminase (AST) and alanine transaminase (ALT), cholesterol content, high density lipoprotein (HDL) and low density lipoprotein (LDL) content, triglycerides content, activity of creatine kinase (CK) and CK-MB, activity of cholinesterase (CHE) and lactate dehydrogenase (LDH), total bile acid (TBA) in high dose feeding group were significantly different. And body weight of mice fed by the flavor was decreased distinctly, and the heart weight was also decreased, while the liver weight was increased obviously. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver and heart were significantly decreased, while methane dicarboxylic aldehyde (MDA) contents were increased evidently. Acrylamide was detected by high performance liquid-mass spectrum (HPLC-MS), and the content was 5.21 mg/kg 3,4-benzoapryene was calculated by HPLC with fluorescence detector, and the content was 21.13 µg/kg. Thus, the roast duck flavor was considered to be potential toxicity to human being.

Anti-proliferation effects of ethanolic extracts from Sophora moorcroftiana seeds on human hepatocarcinoma HepG2 cell line.

Previous studies have shown that the ethanolic extracts from Sophora moorcroftiana seeds (ee-Sms) have in vitro anticancer properties. The anti-proliferation effects of ee-Sms on HepG2 cells were assessed by MTT assay and cell cycle analysis. Total cell proteins were separated by two-dimensional electrophoresis (2-DE), and protein spots with more than two-fold difference were analysed by MALDI-TOF/TOF-MS. MTT assay showed that the anti-proliferation of ee-Sms demonstrates dose- and time dependently. HepG2 cells were treated with ee-Sms at 1.30 mg/mL for 48 h induced cell cycle arrest in S phase. The differentially-expressed proteins were involved in DNA repair, cell proliferation, cell metabolism and immunoreaction. This study sheds new insights into the molecular mechanisms underlying the anti-proliferation properties of ee-Sms in HepG2 cells.

Exploring brusatol as a new anti-pancreatic cancer adjuvant: biological evaluation and mechanistic studies.

Pancreatic cancer is highly resistant to chemotherapeutic agents and is known to have a poor prognosis. The development of new therapeutic entities is badly needed for this deadly malignancy. In this study, we demonstrated for the first time that brusatol, a natural quassinoid isolated from a Chinese herbal medicine named Bruceae Fructus, possessed potent cytotoxic effect against different pancreatic adenocarcinoma cell lines. Its anti-pancreatic cancer effect was comparable to that of the first-line chemotherapeutic agents such as gemcitabine and 5-fluorouracil, with a more favorable safety profile. In addition, brusatol showed a synergistic anti-proliferative effect toward PANC-1 and Capan-2 cell lines when combined with gemcitabine or 5-fluorouracil. The results of flow cytometry suggested that brusatol combination treatment with gemcitabine or 5-fluorouracil was able to cause cell cycle arrest at G2/M phase, and accentuate apoptosis in PANC-1 cells. Moreover, brusatol deactivated gemcitabine/5-fluorouracil-induced NF-κB activation. Western blot analysis and qRT-PCR results showed that brusatol significantly down-regulated the expression of vimentin and Twist, and markedly stimulated the expression of E-cadherin, the key regulatory factors of the epithelial-mesenchymal transition process. Furthermore, treatment with combination of brusatol and gemcitabine or 5-fluorouracil significantly reduced in vivo tumor growth when compared with treatment of either brusatol or gemcitabine/5-fluorouracil alone. Taken together, these results have amply demonstrated that brusatol is a potent anti-pancreatic cancer natural compound, and the synergistic anti-pancreatic cancer effects of brusatol and gemcitabine/5-fluorouracil observed both in vitro and in vivo are associated with the suppression of epithelial-mesenchymal transition process, indicating that brusatol is a promising adjunct to the current chemotherapeutic regimen.

Comparison of efficacy and safety of hyoscine butylbromide versus anisodamine for acute gastric or intestinal spasm-like pain: A randomized, double-blinded, multicenter Phase III trial.

OBJECTIVE: Acute gastric or intestinal spasm-like pain is common in clinical setting. Hyoscine butylbromide (HBB), an anti-cholinergic agent, relieves pain in stomach and bowel cramps by inhibiting smooth muscle contractility. In this study, we aimed to compare the efficacy and safety of parenteral HBB and anisodamine for treating acute gastric or intestinal pain. METHODS: In this randomized, controlled, double-blind, parallel-group, multicenter non-inferiority trial, 299 Chinese patients were randomly assigned to HBB or anisodamine in a ratio of 1:1. They were administrated a single dose of either HBB 20 mg or anisodamine 10 mg, and a second dose was given when needed. The primary end-point was the difference in pain intensity (PID) from the pre-dose baseline at 20 min after the first injection. RESULTS: Altogether 295 patients completed the protocol (153 in the HBB and 142 in the anisodamine group). For the primary end-point, the PID was -4.09 (95% confidence interval [CI]: -4.41, -3.76) for the HBB group and -3.66 (95% CI: -4.02, -3.31) for the anisodamine group (P < 0.0001 for non-inferiority). The percentage of patients with at least one adverse event was lower in the HBB group than in the anisodamine group (13.1% vs 17.6%), but there was no statistical significance (P = 0.279). The most frequent adverse events were thirst (7.8%) and dry mouth (2.6%) in the HBB group, and thirst (7.0%), dry mouth (3.5%) and nodal arrhythmia (2.1%) in the anisodamine group. CONCLUSIONS: HBB 20 mg was not inferior to anisodamine 10 mg in pain relief of patients with acute gastric or intestinal spasm-like pain. Both drugs were safe and well tolerated.

Non-thermal plasma treatment of Radix aconiti wastewater generated by traditional Chinese medicine processing.

The wastewater effluent from Radix aconiti processing, an important step in the production processes of traditional Chinese medicine (TCM), is a type of toxic wastewater and difficult to treat. Plasma oxidation methods have emerged as feasible techniques for effective decomposition of toxic organic pollutants. This study examined the performance of a plasma reactor operated in a dielectric barrier discharge (DBD) to degrade the effluent from R. aconiti processing. The effects of treatment time, discharge voltage, initial pH value and the feeding gas for the reactor on the degradation of this TCM wastewater were investigated. A bacterium bioluminescence assay was adopted in this study to test the toxicity of the TCM wastewater after non-thermal plasma treatment. The degradation ratio of the main toxic component was 87.77% after 60min treatment with oxygen used as feed gas and it was 99.59% when the initial pH value was 8.0. High discharge voltage and alkaline solution environment were beneficial for improving the degradation ratio. The treatment process was found to be capable of reducing the toxicity of the wastewater to a low level or even render it non-toxic. These experimental results suggested that the DBD plasma method may be a competitive technology for primary decomposition of biologically undegradable toxic organic pollutants in TCM wastewater.

Intravenous Esomeprazole for Prevention of Peptic Ulcer Rebleeding: A Randomized Trial in Chinese Patients.

INTRODUCTION: High-dose intravenous esomeprazole is the only approved pharmacological treatment for the prevention of peptic ulcer rebleeding (currently approved in over 100 countries worldwide), but has not yet been approved in China. This study aimed to evaluate a high-dose esomeprazole intravenous regimen vs. an active control (cimetidine) for the prevention of rebleeding in Chinese patients with a high risk of peptic ulcer rebleeding who had undergone primary endoscopic hemostatic treatment. METHODS: This was a parallel-group study conducted at 20 centers in China. The study comprised a randomized, double-blind, intravenous treatment phase of 72 h in which 215 patients received either high-dose esomeprazole (80 mg + 8 mg/h) or cimetidine (200 mg + 60 mg/h), followed by an open-label oral treatment phase in which all patients received esomeprazole 40 mg tablets once daily for 27 days. The primary outcome was the rate of clinically significant rebleeding within the first 72 h after initial endoscopic hemostatic therapy. Secondary outcomes included the rates of clinically significant rebleeding within 7 and 30 days; proportions of patients who had endoscopic retreatment and other surgery due to rebleeding; and number of blood units transfused. RESULTS: The rate of clinically significant rebleeding within 72 h was low overall (3.3%) and numerically lower in patients treated with esomeprazole compared with cimetidine (0.9% vs. 5.6%). Overall, the results of the secondary outcomes also showed a numerical trend towards superiority of esomeprazole over cimetidine. All treatments were well tolerated. CONCLUSION: In this phase 3, multicenter, randomized trial conducted in China, esomeprazole showed a numerical trend towards superior clinical benefit over cimetidine in the prevention of rebleeding in patients who had successfully undergone initial hemostatic therapy of a bleeding peptic ulcer, with a similar safety and tolerability profile. These findings suggest that esomeprazole may be an alternative treatment option to cimetidine for this indication in China. FUNDING: AstraZeneca. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01757275.

The efficacy of Combizym in the treatment of Chinese patients with dyspepsia: a multicenter, randomized, placebo-controlled and cross-over study: Shanghai Combizym Clinical Cooperative Group.

OBJECTIVE: To evaluate the efficacy and safety of Combizym treatment in Chinese patients with dyspepsia. METHODS: In this multicenter, randomized, placebo-controlled cross-over study, a total of 151 patients (76 men and 75 women, mean age: 44.67 +/- 6.46 years, range: 22-67 years) with dyspepsia whose symptoms were not relieved by placebos were recruited. They were randomly divided into group A (79 patients, 2 weeks of Combizym treatment, two tablets post-meal, t.i.d.; then 1 week of wash-out, followed by 2 weeks of placebo treatment, two tablets post-meal, t.i.d.) or group B (72 patients, 2 weeks of placebo treatment, two tablets post-meal, t.i.d. then one week of wash-out, followed by 2 weeks of Combizym treatment, 2 tablets post-meal, t.i.d.). The index of severity of the dyspepsia symptoms was evaluated before and after each treatment phase with Combizym or the placebo. RESULTS: Compared with the placebo, 2 weeks of Combizym treatment decreased the severity index of dyspepsia symptoms significantly (27.64 +/- 1.77 to 9.72 +/- 1.33 vs 23.99 +/- 1.28 to 22.03 +/- 1.40, P < 0.01). The efficacy rates of Combizym and the placebo on dyspepsia were 89.63% and 21.68%, respectively (P < 0.01). According to the improvement of symptoms index, individual dyspepsia symptoms that could be attenuated by Combizym therapy were anepithymia, abdominal distension, belching, diarrhea, abdominal pain, epigastric burning. None of patients reported adverse events during the study. CONCLUSION: Combizym treatment effectively ameliorates dyspepsia symptoms in Chinese patients, with satisfactory safety and compliance.

[Red peony root decoction in treatment of severe acute pancreatitis: a randomized controlled trial].

OBJECTIVE: To compare the therapeutic effects of red peony root decoction, a compound traditional Chinese herbal medicine, and rhubarb in treating severe acute pancreatitis (SAP). METHODS: A total of 96 consecutive patients with objectively-graded SAP were randomly divided into treatment and control groups. There were 48 cases in each group. The patients in the treatment and control groups were assigned to receive red peony root decoction and rhubarb treatment 1-2 times a day via a gastric tube respectively. Comparisons in the time needed for the disappearance of abdominal tenderness, fever and abdominal distension were made between the two groups. The total days of using antibiotics, enzyme inhibitor, protease inhibitor, and nasojejunal feeding start, nasojejunal feeding, gastrointestinal decompression, fasting diet were also compared. And comparison also included hospital stays and hospitalization costs. RESULTS: The durations of abdominal tenderness, fever and abdominal distension in the treatment group were less than those in the control group (P<0.05). Compared with the control group, the time length for antibiotics (including anti-bacteria drug and antifungal agent) use, nasojejunal feeding start, nasojejunal feeding, gastrointestinal decompression, fasting diet, hospital stays and hospitalization costs were decreased in the treatment group (P<0.05). There were no significant differences between the two groups in enzyme inhibitor and protease inhibitor requirement, mortality and adverse reactions. CONCLUSION: Red peony root decoction is more effective than rhubarb alone for SAP patients.