Preliminary investigation on the causes of red tides in Qinhuangdao coastal areas in 2022.

To explore the causes of red tides in Qinhuangdao coastal water, we conducted surveys on both water quality and red tides during April to September of 2022 and analyzed the relationships between main environmental factors and red tide organisms through the factor analysis and canonical correspondence analysis. The results showed that there were eight red tides along the coast of Qinhuangdao in 2022, with a cumulative blooming area of 716.1 km2. The red tides could be divided into three kinds based on the major blooming organisms and occurrence time, Noctiluca scintillans bloom, diatom-euglena (Skeletonema costatum, Eutreptiella gymnastica, Pseudo-nitzschia spp.) bloom, and dinoflagellate (Scrippsiella trochoidea and Ceratium furca) bloom. Seasonal factor played roles mainly during July to September, while inorganic nutrients including nitrogen and phosphorus influenced the blooms mainly in April and July. The canonical correspondence analysis suggested that N. scintillans preferred low temperature, and often bloomed with high concentrations of ammonium nitrogen and dissolved inorganic phosphorus. S. costatum, E. gymnastica, and Pseudo-nitzschia spp. could tolerate broad ranges of various environmental factors, but favored high temperature and nitrogen-rich seawater. C. furca and S. trochoidea had higher survival rate and competitiveness in phosphate-poor waters. Combined the results from both analyses, we concluded that the causes for the three kinds of red tide processes in Qinhuangdao coastal areas in 2022 were different. Adequate diet algae and appropriate water temperature were important factors triggering and maintaining the N. scintillans bloom. Suitable temperature, salinity and eutrophication were the main reasons for the diatom-euglena bloom. The abundant nutrients and seawater disturbance promoted the germination of S. trochoidea cysts, while phosphorus limitation caused the blooming organism switched to C. furca and maintained the bloom hereafter.

[Mechanism of n-butanol fraction of Wenxia Formula combining with gefitinib in treating non-small cell lung cancer based on network pharmacology and in vitro experiment].

This study combined network pharmacology, molecular docking, and in vitro experiments to explore the potential mechanism of the active components of the n-butanol fraction of Wenxia Formula(NWXF) combined with gefitinib(GEF) in treating non-small cell lung cancer(NSCLC). Ultra-performance liquid chromatography-quadrupole Orbitrap mass spectrometry(UPLC-Q-Orbitrap MS) was employed to detect the main chemical components of NWXF. The active components of NWXF were retrieved from SwissADME, and the candidate targets of these active components were retrieved from SwissTargetPrediction. Online Mendelian Inheritance in Man(OMIM) and GeneCards were searched for the targets of NSCLC. Cytoscape 3.9.0 and STRING were employed to build the protein-protein interaction(PPI) network with the common targets shared by NWXF and NSCLC. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment were performed in DAVID to predict the potential mechanisms. Finally, molecular docking between the main active ingredients and key targets was conducted in SYBYL-X 2.0. The methyl thiazolyl tetrazolium(MTT) assay was employed to evaluate the inhibitory effects of NWXF and/or GEF on the proliferation of human non-small cell lung cancer cells(A549 and PC-9). Additionally, the impact of NWXF on human embryonic lung fibroblast cells(MRC-5) was assessed. The effectiveness of the drug combination was evaluated based on the Q value. The terminal-deoxynucleoitidyl transferase mediated nick-end labeling(TUNEL) assay was employed to examine the apoptosis of A549 and PC-9 cells treated with NWXF and/or GEF. Quantitative real-time PCR(qRT-PCR) was employed to measure the mRNA levels of epidermal growth factor receptor(EGFR), c-Jun N-terminal kinase(JNK), and Bcl2-associated X protein(Bax) in the A549 and PC-9 cells treated with NWXF and/or GEF. Western blot was employed to determine the protein levels of EGFR, p-EGFR, JNK, p-JNK, and Bax in the A549 and PC-9 cells treated with NWXF and/or GEF. A total of 77 active components, 488 potential targets, and 49 key targets involved in the treatment of NSCLC with NWXF were predicted. The results of GO annotation showed that NWXF may treat NSCLC by regulating the biological processes such as cell proliferation, apoptosis, and protein phosphorylation. KEGG enrichment revealed that the key targets of NWXF in treating NSCLC were enriched in the mitogen-activated protein kinase(MAPK), phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT), hypoxia-inducible factor-1(HIF-1), and microRNA-related signaling pathways. Molecular docking results showed that 91.9% of the docking scores were greater than 5, indicating the strong binding capability between main active components and key targets. The cell experiments demonstrated that NWXF combined with GEF synergistically inhibited the proliferation, promoted the apoptosis, decreased p-EGFR/EGFR and p-JNK/JNK values, down-regulated the mRNA levels of EGFR and JNK, and up-regulated the mRNA and protein levels of Bax in A549 and PC-9 cells. In conclusion, NWXF combined with GEF can regulate the EGFR/JNK pathway to promote the apoptosis of NSCLC cells, thus treating NSCLC.

Synergistic ultrasound pulsed electric field extraction of litchi peel polyphenols and determination of their properties.

The effects of pulsed electric field combined with ultrasound (PEF-US) on the recovery of polyphenols from litchi peels were investigated. In addition, the optimal purification parameters for polyphenol extracts and their biological activities were also explored in this study. Single-factor and orthogonal experiments were used to optimize the extraction conditions of polyphenols. After optimization, the total phenol content (TPC) of the sample extracted by PEF-US was 2.30 times higher than that of the sample extracted by traditional hot-water extraction. The mechanism of PEF-US enhancing polyphenol recovery was also revealed by morphological analysis of the powder surface. LX-7 was the best resin by comparing the purification effect of nine macroporous resins. The optimum conditions for purification of litchi peel polyphenols by LX-7 resin were also optimized through adsorption and desorption experiments. UHPLC-MS and HPLC results revealed that gentisic acid, catechin, procyanidin A2 and procyanidin B1 are four main substances in purified samples. The results of bioactivity experiments showed that the purified polyphenol samples had strong antioxidant and antibacterial activity. Overall, PEF-US is an efficient method for recovering polyphenols from litchi peels. Our study also provides a strategy for the comprehensive utilization of fruit processing waste.

Lysidrhodosides A-I, acylphloroglucinol glucosides with anti-inflammatory activities from the leaves of Lysidice rhodostegia.

Lysidrhodosides A-I (1-9), nine acylphloroglucinol glucoside derivatives along with three known analogues (10-12) were isolated from the leaves of Lysidice rhodostegia. Their structures and absolute configuration were elucidated by spectroscopic data analysis (NMR, UV, IR, HR-ESI-MS), single-crystal X-ray diffraction, and acid hydrolysis with HPLC analysis. Notably, compounds 7-9 represent the first examples of 3-methylbutyryl phloroglucinol glucoside dimers isolated from this plant. Additionally, compounds 1-12 were assessed for their inhibitory effects on nitric oxide (NO) in the LPS-induced BV-2 cells. The results showed that compounds 6 and 12 significantly inhibited the production of the inflammatory mediator NO, with an inhibitory rate of 95.96 and 91.13% at a concentration of 50 µM, respectively.

The Psychosomatic Traits of "People with the Five Elements in Traditional Chinese Medicine": A Qualitative Study.

Objective: To identify the representative attributes of the five elements of a person with a qualitative methodology and provide the basis for the clinical diagnosis and treatment of "people with the five elements in traditional Chinese medicine (TCM)." Methods: Data collected from the literature review, two sessions of brainstorming of experts with related experience in "people with the five elements in TCM" from October 2020 to December 2020, and six rounds of in-depth interviews with 30 participants who had various attributes of the five elements from March 2021 to October 2021 were analyzed. Triangulation was used in this study, and theming and synthesizing were used to analyze the data. Results: A total of 31 experts and 30 interviewees participated in this study. The median age of the experts and interviewees were 48.0 and 38.5 years, respectively; 51.66% and 54.8% of experts and interviewees, respectively, were men. The descriptors of facial diagrams of "people with the five elements in TCM" were complexion, shape, distribution state of facial bones, convergence trend of facial muscles, and facial expression. A theoretical model of "people with the five elements in TCM" was shaped based on these findings. Conclusion: The study suggests a possibility for bridging the gap between personality and bodily state, identifying an avenue for personality research from the perspective of TCM.

Influence of different heat transfer models on therapeutic temperature prediction and heat-induced damage during magnetic hyperthermia.

Magnetic hyperthermia regulates the therapeutic temperature within a specific range to damage malignant cells after exposing the magnetic nanoparticles inside tumor tissue to an alternating magnetic field. The therapeutic temperature of living tissues can be generally predicted using Pennes' bio-heat equation after ignoring both the inhomogeneity of biological structure and the microstructural responses. Although various of the bio-heat transfer models proposed in literature fix these shortages, there is still a lack of a comprehensive report on investigating the discrepancy for different models when applied in the magnetic hyperthermia context. This study compares four different bio-heat equations in terms of the therapeutic temperature distribution and the heat-induced damage situation for a proposed geometric model, which is established based on computed tomography images of a tumor bearing mouse. The therapeutic temperature is also used as an index to evaluate the effect of two key relaxation times for the phase lag behavior on bio-heat transfer. Moreover, this work evaluates the effects of two blood perfusion rates on both the treatment temperature and the cumulative equivalent heating minutes at 43 °C. Numerical analysis results reveal that relaxation times for phase-lag behavior as well as the porosity for living tissues directly affect the therapeutic temperature variation and ultimately the thermal damage for the malignant tissue during magnetic hyperthermia. The dual-phase-lag equation can be converted into Pennes' equation and simple-phase-lag equation when relaxation times meet specific conditions during the process of heat transfer. In addition, different blood perfusion rates can result in an amplitude discrepancy for treatment temperature, but this parameter does not change the characteristics of thermal propagation during therapy.

Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9.

OBJECTIVE: To explore whether the ethanol extract of Herpetospermum caudigerum Wall (EHC), a Xizang medicinal plant traditionally used for treating liver diseases, can improve imiquimod-induced psoriasis-like skin inflammation. METHODS: Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice. The protein levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-17A (IL-17A) in mouse skin samples were examined using immunohistochemical staining. In vitro, IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1 (ICAM-1) and chemokine CXC ligand 9 (CXCL9) using Western blotting and reverse transcription-quantitative polymerase chain reaction. The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9. RESULTS: EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ, TNF-α, and IL-17A in psoriatic lesions. Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes. Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin-proteasome-mediated protein degradation rather than transcriptional repression. Seven primary compounds including ehletianol C, dehydrodiconiferyl alcohol, herpetrione, herpetin, herpetotriol, herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry. CONCLUSION: Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites. Please cite this article as: Zhong Y, Zhang BW, Li JT, Zeng X, Pei JX, Zhang YM, Yang YX, Li FL, Deng Y, Zhao Q. Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9. J Integr Med. 2023; 21(6): 584-592.

Efficacy of five-step shoulder manipulation for rotator cuff-related shoulder pain: protocol for a multicenter randomized controlled trial.

BACKGROUND: Rotator cuff-related shoulder pain (RCRSP) is the most common cause of shoulder disorders. In China, manipulation has been used extensively for the treatment of patients with RCRSP. However, high-quality clinical evidence to support the therapeutic effect of manipulation is still limited. METHODS: A multicenter, participant-, outcome assessor-, and data analyst-blinded, randomized, placebo-controlled trial will be conducted. A total of 280 participants with RCRSP will be recruited from three hospitals and randomly assigned to a five-step shoulder manipulation (FSM) group or a sham manipulation (SM) group. Each group will receive four weekly treatment sessions, with all participants performing exercises at home for 12 weeks. Assessments, namely the Constant-Murley score, visual analog scale, range of motion, and 36-Item Short Form Survey, will be made at baseline, 4, 12, 18, and 24 weeks. Adverse events during the study will also be recorded. DISCUSSION: This is a pragmatic clinical trial to evaluate the efficacy and safety of FSM in patients with RCRSP. The findings of this study will provide worthy clinical evidence for manual therapy for RCRSP. TRIAL REGISTRATION: China Registered Clinical Trial Registration Center ChiCTR2000037577. Registered on 29 August 2020.

Network meta-analysis of the treatment safety and efficacy of different energy systems in prostate vaporization.

Many clinical trials and meta-analyses have examined vaporization with different energy instruments has been recognized by the American Urological Association (AUA) and the European Association of Urology (EAU) as a promising treatment for benign prostate hyperplasia. However, there is still a lack of evidence for a network comparison between different vaporization devices. The PubMed, Embase, Cochrane and Web of Science databases were searched to identify randomized controlled trials (RCTs) of different energy systems for prostate vaporization. Pairwise and network meta-analyses (NMA) were performed to analyze the outcome regarding surgery time, complications, short-term maximum urine flow rate (Qmax), and long-term Qmax. The Stata software was used for paired meta-analysis. A Bayesian NMA model with ADDIS software was applied to achieve the indirect comparison of different energy systems. Node-splitting analysis and inconsistency factors were used to test inconsistency for closed-loop indirect comparison. Fifteen studies were included in this study, involving three types of energy systems used in prostate vaporization: diode laser (wavelength: 980 nm, power: 200-300 W, mode: continuous), green-light laser (wavelength: 532 nm, power: 80-180 W, mode: continuous), and bipolar plasma vaporization (bipolar electrode, power: 270-280 W, mode: pulsed). In the conventional paired meta-analysis, significantly better short-term efficacy was found in green light laser vaporization, while no significant difference was detected in other parameters. According to the results of the NMA, a greenlight laser is recommended for prostate vaporization rather than the other two systems. When considering operation time, overall complications, short-term Qmax, and long-term Qmax, there were no significant differences among green-light laser vaporization, diode laser vaporization, and bipolar vaporization in BPH treatment. However, according to the probability ranking and benefit-risk analysis results, the green-light laser might be the best energy system for prostate vaporization in BPH treatment.

Metabolic profiles in plasma of patients with herpes labialis based on GC-MS.

OBJECTIVE: This study aims to compare the plasma metabolic profiles of patients with herpes labialis with healthy controls and identify the biomarkers of herpes labialis. SUBJECTS AND METHODS: We collected 18 patients with herpes labialis and 20 healthy individuals. Plasma samples from both groups were analyzed using gas chromatography-mass spectrometry (GC-MS). RESULTS: According to the principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), we found that metabolic profiles had changed in patients with herpes labialis compared to the controls. By further selecting the different metabolites according to the variable importance in the projection (VIP) and p valve of t-tests, we found that acetic acid, pyroglutamic acid, alanine, ethanedioic acid, cyclohexaneacetic acid, pyruvic acid, d-mannose, phosphoric acid, l-amphetamine, and citric acid were decreased in patients with herpes labialis, while sedoheptulose and ethylamine were increased. Pathway analysis showed that herpes labialis may affect the amino acid and energy metabolism. CONCLUSIONS: Our findings may contribute to elucidating the metabolic basis of herpes labialis and provide a new perspective for further research on the "Shang-Huo" state in traditional Chinese medicine (TCM).

Non-thermal plasma-treated melatonin inhibits the biological activity of HCC cells by increasing intracellular ROS levels and reducing RRM2 expression.

Non-thermal plasma (NTP) is thought to have a cytotoxic effect on tumor cells. Although its application in cancer therapy has shown considerable promise, the current understanding of its mechanism of action and cellular responses remains incomplete. Furthermore, the use of melatonin (MEL) as an adjuvant anticancer drug remains unexplored. In this study, we found that NTP assists MEL in promoting apoptosis, delaying cell cycle progression, and inhibiting cell invasion and migration in hepatocellular carcinoma (HCC) cells. This mechanism may be associated with the regulation of intracellular reactive oxygen species levels and ribonucleotide reductase regulatory subunit M2 expression. Our findings confirm the pharmacological role of MEL and the adjuvant value of NTP, emphasizing their potential in combination therapy for HCC. Our study may have important implications for the development of new approaches for HCC treatment.

Synthesis and biological evaluation of ruthenium complexes containing phenylseleny against Gram-positive bacterial infection by damage membrane integrity and avoid drug-resistance.

Compounds modified with selenium atom as potential antibacterial agents have been exploited to combat the nondrug-resistant bacterial infection. In this study, we designed and synthesized four ruthenium complexes retouching of selenium-ether. Fortunately, those four ruthenium complexes shown excellent antibacterial bioactive (MIC: 1.56-6.25 µg/mL) against Staphylococcus aureus (S. aureus), and the most active complex Ru(II)-4 could kill S. aureus by targeting the membrane integrity and avoid the bacteria to evolve drug resistance. Moreover, Ru(II)-4 was found to significantly inhibit the formation of biofilms and biofilm eradicate capacity. In toxicity experiments, Ru(II)-4 exhibited poor hemolysis and low mammalian toxicity. To illustrate the antibacterial mechanism: we conducted scanning electron microscope (SEM), fluorescent staining, membrane rupture and DNA leakage assays. Those results demonstrated that Ru(II)-4 could destroy the integrity of bacterial cell membrane. Furthermore, both G. mellonella wax worms infection model and mouse skin infection model were established to evaluate the antibacterial activity of Ru(II)-4 in vivo, the results indicated that Ru(II)-4 was a potential candidate for combating S. aureus infections, and almost non-toxic to mouse tissue. Thus, all the results indicated that introducing selenium-atom into ruthenium compounds were a promising strategy for developing interesting antibacterial agents.

T-2 toxin-induced intestinal damage with dysregulation of metabolism, redox homeostasis, inflammation, and apoptosis in chicks.

T-2 toxin is a worldwide problem for feed and food safety, leading to livestock and human health risks. The objective of this study was to explore the mechanism of T-2 toxin-induced small intestine injury in broilers by integrating the advanced microbiomic, metabolomic and transcriptomic technologies. Four groups of 1-day-old male broilers (n = 4 cages/group, 6 birds/cage) were fed a control diet and control diet supplemented with T-2 toxin at 1.0, 3.0, and 6.0 mg/kg, respectively, for 2 weeks. Compared with the control, dietary T-2 toxin reduced feed intake, body weight gain, feed conversion ratio, and the apparent metabolic rates and induced histopathological lesions in the small intestine to varying degrees by different doses. Furthermore, the T-2 toxin decreased the activities of glutathione peroxidase, thioredoxin reductase and total antioxidant capacity but increased the concentrations of protein carbonyl and malondialdehyde in the duodenum in a dose-dependent manner. Moreover, the integrated microbiomic, metabolomic and transcriptomic analysis results revealed that the microbes, metabolites, and transcripts were primarily involved in the regulation of nucleotide and glycerophospholipid metabolism, redox homeostasis, inflammation, and apoptosis were related to the T-2 toxin-induced intestinal damage. In summary, the present study systematically elucidated the intestinal toxic mechanisms of T-2 toxin, which provides novel ideas to develop a detoxification strategy for T-2 toxin in animals.

AGI grade-guided chaiqin chengqi decoction treatment for predicted moderately severe and severe acute pancreatitis (CAP trial): study protocol of a randomised, double-blind, placebo-controlled, parallel-group, pragmatic clinical trial.

BACKGROUND: Acute pancreatitis (AP) is a common digestive disease with increased incidence globally but without internationally licenced pharmacological therapy. Moderately severe and severe acute pancreatitis (MSAP/SAP) contributes predominately for its morbidities and mortality and has been managed in West China Hospital for decades using the traditional Chinese medicinal formula chaiqin chengqi decoction (CQCQD). The current study tests whether the early administration of CQCQD will result in improved clinical outcomes in predicted MSAP/SAP patients. METHODS: This is a single-centre, randomised, controlled, double-blind pragmatic clinical trial. AP patients aged 18-75 admitted within 72 h of onset will be assessed at admission for enrolment. We excluded the predicted mild acute pancreatitis (Harmless Acute Pancreatitis Score > 2 at admission) and severe organ failure (Sequential Organ Failure Assessment [SOFA] score of respiratory, cardiovascular, or renal systems > 3) at admission. Eligible patients will be randomly allocated on a 1:1 basis to CQCQD or placebo control administration based on conventional therapy. The administration of CQCQD and placebo is guided by the Acute Gastrointestinal Injury grade-based algorithm. The primary outcome measure will be the duration of respiratory failure (SOFA score of respiratory system ≥ 2) within 28 days after onset. Secondary outcome measures include occurrence of new-onset any organ failure (SOFA score of respiratory, cardiovascular, or renal system ≥ 2) and new-onset persistent organ failure (organ failure lasts > 48 h), dynamic surrogate biochemical markers and clinical severity scores, gut-centred treatment modalities, local complications status, intensive care need and duration, surgical interventions, mortality, and length of hospital stay. Follow-up will be scheduled on 6, 12, and 26 weeks after enrolment to assess AP recurrence, local complications, the requirement for surgical interventions, all-cause mortality, and patient-reported outcomes. DISCUSSION: The results of this study will provide high-quality evidence to appraise the efficacy of CQCQD for the early management of AP patients. TRIAL REGISTRATION: Chictr.org.cn Registry ( ChiCTR2000034325 ). Registered on 2 July, 2020.

[GAO Wei-bin's clinical experience in treatment of medulla oblongata paralysis with nape acupuncture].

This paper introduces GAO Wei-bin's academic thought in treatment of medulla oblongata paralysis with acupuncture. Through analyzing the etiologies and locations of medulla oblongata paralysis, in accordance with "selecting the nearby acupoints of the affected area", the acupoints are selected from the nape region, the nape acupuncture therapy and the corresponding new points are developed. Based on the human anatomy of the nape region, the anatomic structures of new points (e.g. Gongxue, Tunyan-1, Tunyan-2, Fayin, Zhiqiang and Tiyan) and their effect mechanism are explained. The treatment principle, "distinguishing the symptoms from the root causes, mutual treatment for both symptoms and root causes", is proposed, and the importance of electric stimulation of nape acupuncture is suggested in treatment of medulla oblongata paralysis.

Chemical constituents from mushroom Geoglossum fallax and their bioactive activities.

Chemical investigation on the fruiting bodies of the mushroom Geoglossum fallax led to the isolation of two carboxamides, geoglamides A and B (1 and 2), one meroterpenoid, geoglol A (3), together with seven known metabolites (4-10). Their structures were identified by spectroscopic analyses as well as ECD calculations. Compounds 1 and 2 are rare long chain fatty amides containing a 4-oxo-1,4-dihydropyridine moiety, while compound 3 is a rare C6-C5 type meroterpenoid. Compound 1 displayed cytotoxic activity against human MCF-7 cells with an IC50 value of 25.9 ± 0.51 µM. compounds 2 and 8 showed weak pancreatic lipase inhibition activity. To our best knowledge, this is the first report of the chemical constituents in the genera Geoglossum and their bioactive activity.

Comparative Study on the Clinical Effects of Different Surgical Methods in the Treatment of Gastrointestinal Stromal Tumors.

Objective: The objective is to compare the clinical efficacy of laparoscopic resection (LAP), endoscopic full-thickness resection (EFR), and endoscopic submucosal dissection (ESD) in the treatment of gastrointestinal stromal tumors. Methods: The clinical data of 105 patients who were treated in our hospital and diagnosed with GIST by pathology after surgery from March 2019 to March 2021 were collected. Patients were divided into the LAP group, EFR group, and ESD group according to different surgical methods. The clinical data, surgical conditions, complications, and postoperative conditions of the patients were recorded retrospectively. Patients were followed up closely after surgery. Results: The operation time of the EFR group and ESD group was shorter than that of the LAP group, and the operation time of the EFR group was shorter than that of the ESD group (P < 0.05). The amount of intraoperative blood loss in the EFR group and ESD group was lower than that in the LAP group (P < 0.05). There was no significant difference in the complete resection rate among the three groups (P > 0.05). There was no significant difference in the total incidence of complications among the three groups (P > 0.05). The postoperative abdominal pain time, postoperative hospital stay, and total hospitalization costs of the EFR group and ESD group were lower than those of the LAP group (P < 0.05). No recurrence or metastasis cases were found in the three groups during the follow-up period, and there were no GIST-related deaths in the three groups. Conclusion: LAP, EFR, and ESD have good curative effect, good safety, and good prognosis in the treatment of GIST. But compared with LAP, EFR and ESD have the advantages of less trauma, faster recovery, shorter hospitalization time, and lower hospitalization cost.

miR-214-3p Protects and Restores the Myocardial Tissue of Rat Myocardial Infarction Model by Targeting PTEN.

Myocardial infarction (MI), which results in myocardial cell dysfunction and irreversible loss, is one of the most serious health threats today. This study was started with rats, by which the consequence of miRNA expression dysregulation to the occurrence and progression of cardiovascular diseases was explored. We first conducted miRNA sequencing on the myocardial tissues separately from myocardial infarction treatment and sham operation treatment to clarify those differently expressed miRNAs; then, our experiment of functional verification of those key miRNAs was initiated so as to dig out the molecular mechanism behind the miRNA's regulation in myocardial infarction. And it turned out that there were 32 upregulated miRNAs and 16 downregulated miRNAs according to our comparison from the myocardial infarction model group to the sham operation group; of all those upregulated, alteration in miR-214-3p expression was the most conspicuous. Overexpression of miR-214-3p greatly alleviated myocardial infarct area and ameliorated myocardial tissue structure, even reducing myocardial fibrosis and the devastation in the tissues. On the molecular level, miR-214-3p overexpression brought down both the apoptosis rate and cleaved caspase 3 expression. Besides that, we verified that PTEN is the target gene of miR-214-3p through a dual-luciferase assay. A cotransfection of miR-214-3p and PTEN brought about an obvious elevation in the myocardial infarct area, tissue damage, and fibrosis, even in the aspect of cellular apoptosis than a mere transfection of miR-214-3p. All the results above verified miR-214-3p's effects in protecting myocardial tissues and reducing the infarct area, and it was reasonable to assume that those functions of miR-214-3p came into effect by targeting PTEN, which was then justified by the inversion to miR-214-3p's protection via PTEN overexpression.

Transcriptomics and Network Pharmacology Reveal the Protective Effect of Chaiqin Chengqi Decoction on Obesity-Related Alcohol-Induced Acute Pancreatitis via Oxidative Stress and PI3K/Akt Signaling Pathway.

Obesity-related acute pancreatitis (AP) is characterized by increasing prevalence worldwide and worse clinical outcomes compared to AP of other etiologies. Chaiqin chengqi decoction (CQCQD), a Chinese herbal formula, has long been used for the clinical management of AP but its therapeutic actions and the underlying mechanisms have not been fully elucidated. This study has investigated the pharmacological mechanisms of CQCQD in a novel mouse model of obesity-related alcohol-induced AP (OA-AP). The mouse OA-AP model was induced by a high-fat diet for 12 weeks and subsequently two intraperitoneal injections of ethanol, CQCQD was administered 2 h after the first injection of ethanol. The severity of OA-AP was assessed and correlated with changes in transcriptomic profiles and network pharmacology in the pancreatic and adipose tissues, and further docking analysis modeled the interactions between compounds of CQCQD and their key targets. The results showed that CQCQD significantly reduced pancreatic necrosis, alleviated systemic inflammation, and decreased the parameters associated with multi-organ dysfunction. Transcriptomics and network pharmacology analysis, as well as further experimental validation, have shown that CQCQD induced Nrf2/HO-1 antioxidant protein response and decreased Akt phosphorylation in the pancreatic and adipose tissues. In vitro, CQCQD protected freshly isolated pancreatic acinar cells from H2O2-elicited oxidative stress and necrotic cell death. The docking results of AKT1 and the active compounds related to AKT1 in CQCQD showed high binding affinity. In conclusion, CQCQD ameliorates the severity of OA-AP by activating of the antioxidant protein response and down-regulating of the PI3K/Akt signaling pathway in the pancreas and visceral adipose tissue.

Dietary folate drives methionine metabolism to promote cancer development by stabilizing MAT IIA.

Folic acid, served as dietary supplement, is closely linked to one-carbon metabolism and methionine metabolism. Previous clinical evidence indicated that folic acid supplementation displays dual effect on cancer development, promoting or suppressing tumor formation and progression. However, the underlying mechanism remains to be uncovered. Here, we report that high-folate diet significantly promotes cancer development in mice with hepatocellular carcinoma (HCC) induced by DEN/high-fat diet (HFD), simultaneously with increased expression of methionine adenosyltransferase 2A (gene name, MAT2A; protein name, MATIIα), the key enzyme in methionine metabolism, and acceleration of methionine cycle in cancer tissues. In contrast, folate-free diet reduces MATIIα expression and impedes HFD-induced HCC development. Notably, methionine metabolism is dynamically reprogrammed with valosin-containing protein p97/p47 complex-interacting protein (VCIP135) which functions as a deubiquitylating enzyme to bind and stabilize MATIIα in response to folic acid signal. Consistently, upregulation of MATIIα expression is positively correlated with increased VCIP135 protein level in human HCC tissues compared to adjacent tissues. Furthermore, liver-specific knockout of Mat2a remarkably abolishes the advocating effect of folic acid on HFD-induced HCC, demonstrating that the effect of high or free folate-diet on HFD-induced HCC relies on Mat2a. Moreover, folate and multiple intermediate metabolites in one-carbon metabolism are significantly decreased in vivo and in vitro upon Mat2a deletion. Together, folate promotes the integration of methionine and one-carbon metabolism, contributing to HCC development via hijacking MATIIα metabolic pathway. This study provides insight into folate-promoted cancer development, strongly recommending the tailor-made folate supplement guideline for both sub-healthy populations and patients with cancer expressing high level of MATIIα expression.