Pitavastatin induces autophagy-dependent ferroptosis in MDA-MB-231 cells via the mevalonate pathway.

Triple-negative breast cancer (TNBC) is more prone to recurrence and metastasis relative to other subtypes of breast cancer, leading to an extremely poor prognosis. The increasing potential chemoresistance of TNBC patients is mainly due to that tumor cells escape from apoptosis. In recent years, statins have demonstrated extensive anti-tumor effects. It is worth noting that statins have more effective anti-tumor effects on TNBC cells and drug-resistant breast cancer cells. Therefore, this study examines the superior cytotoxic effects of statins on TNBC cell lines and further explores their potential therapeutic mechanisms. We detected different cell phenotypes and found that statins significantly reduced the cell viability of TNBC cells. Specifically, pitavastatin showed an obvious induction in cell death, cell cycle arrest and oxidative stress in TNBC MDA-MB-231 cells. The reversal effect of iron chelator desferrioxamine (DFO) on the morphological and molecular biological changes induced by pitavastatin has revealed a new mode of cell death induced by pitavastatin: ferroptosis. This ferroptotic effect was strengthened by the decreased expression of glutathione peroxidase 4 (GPx4) as well as newly discovered ferroptosis suppressor protein 1 (FSP1). The data showed that ferroptotic death of MDA-MB-231 cells is autophagy-dependent and mediated by the mevalonate pathway. Finally, we found that therapeutic oral doses of statins can inhibit the growth of transplanted tumors, which establishes statins as a potential treatment for TNBC patients. In conclusion, we found pitavastatin could induce autophagy-dependent ferroptosis in TNBC cells via the mevalonate pathway which may become a potential adjuvant treatment option for TNBC patients.

[Isolation and identification of chemical constituents from aerial parts of Glycyrrhiza uralensis].

The present study investigated the chemical constituents from the aerial parts of Glycyrrhiza uralensis. The ethanol extract of the aerial parts of G. uralensis was separated and purified by different column chromatographies such as macroporous resin, silica gel, and Sephadex LH-20, and through preparative HPLC and recrystallization. Thirteen compounds were isolated and identified as(2S)-6-[(Z)-3-hydroxymethyl-2-butenyl]-5,7,3'-trihydroxy-4'-methoxy-dihydroflavanone(1),(2S)-8-[(E)-3-hydroxymethyl-2-butenyl]-5,7,3',5'-tetrahydroxy-dihydroflavanone(2), α,α'-dihydro-5,4'-dihydroxy-3-acetoxy-2-isopentenylstilbene(3), 6-prenylquercetin(4), 6-prenylquercetin-3-methyl ether(5), formononetin(6), 3,3'-dimethylquercetin(7), chrysoeriol(8), diosmetin(9),(10E,12Z,14E)-9,16-dioxooctadec-10,12,14-trienoic acid(10), 5,7,3',4'-tetrahydroxy-6-prenyl-dihydroflavanone(11), naringenin(12), dibutylphthalate(13). Compounds 1-3 are new compounds, and compounds 10 and 13 are isolated from aerial parts of this plant for the first time.

[Effects of pH value on stachydrine biosynthesis of hydroponic Leonurus japonicus and its physiological mechanism].

The present study explored the physiological mechanism of the effects of different pH treatments on the growth, physiological characteristics, and stachydrine biosynthesis of Leonurus japonicus to provide references for the cultivation and quality control of L. japonicus. Under hydroponic conditions, different pH treatments(pH 5,6,7,8) were set up. The growth, physiology, and the content of stachydrine and total alkaloids of L. japonicus, as well as the content of key intermediate products in stachydrine biosynthesis pathway(i.e., pyruvic acid, α-ketoglutaric acid, glutamic acid, and ornithine) were monitored to explore the physiological mechanism of the effects of pH on the growth and active components of L. japonicus. The results showed that L. japonicus. could grow normally in the pH 5-8 solution. The pH treatment of neutral acidity was more conducive to the accumulation of photosynthetic pigments and the increase in soluble protein in leaves of L. japonicus. to promote its growth and yield. However, since stachydrine is a nitrogen-containing pyrrolidine alkaloid, its synthesis involves the two key rate-limiting steps of nitrogen addition: reductive ammoniation reaction and Schiff base formation reaction. High pH treatments promote the synthesis and accumulation of substrates and products of the above two reactions, indicating that the alkaline environment can promote the nitrogen addition reaction, thereby promoting the biosynthesis and accumulation of stachydrine.

Effectiveness of Comprehensive Nursing in Hemodialysis of Patients with Chronic Renal Failure and the Impact on Their Quality of Life.

Objective: To assess the effectiveness of comprehensive nursing in patients with chronic renal failure undergoing hemodialysis and the impact on their quality of life. Methods: The present study included 86 patients undergoing hemodialysis for chronic renal failure from January 2020 to October 2021 and randomly assigned them to receive either normal nursing or comprehensive nursing, with 43 cases in each group. Outcome measures included psychological status, treatment compliance, quality of life, and complications of the eligible patients. Results: After the intervention, comprehensive nursing resulted in lower Self-Rating Anxiety Scale (SAS) scores and Self-Rating Depression Scale (SDS) scores and higher quality of life scores for patients versus routine nursing (P < 0.05). Comprehensive nursing was associated with a significantly higher overall patient compliance rate versus routine nursing (P < 0.05). Patients receiving comprehensive nursing had a lower risk of developing complications versus those given routine nursing (P < 0.05). Conclusion: Comprehensive care increases treatment compliance and self-care capacity of patients undergoing hemodialysis for chronic renal failure, improves their quality of life, and lowers the risk of complications, indicating a high potential for clinical advancement.

Comprehensive chemical profiling of the flowers of Citrus aurantium L. var. amara Engl. and uncovering the active ingredients of lipid lowering.

The flowers of Citrus aurantium L. var. amara Engl. (FCAVA) is popularly consumed as an edible tea for anti-hyperlipidemia. But the active ingredients are not fully clear. In this study, ultra-high performance liquid chromatography coupled to quadrupole time of flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) with diagnostic product ions and neutral loss filtering strategy were successfully used for comprehensive characterization of chemical components in FCAVA. A total of 228 constituents, including 46 organic acids, 12 coumarins and 170 flavonoids, were tentatively characterized (30 confirmed with reference standards). Among them, nineteen flavonoids in 70 batches of FCAVA from different geographical origins were quantified by UHPLC tandem triple quadrupole mass spectrometry (QQQ-MS), which displayed satisfactory linearity, sensitivity, precision, accuracy, and stability. According to analytical results, the distribution of nineteen flavonoids in different geographical origins of FCAVA was clarified. In addition, the effect on LDL uptake of twenty-five flavonoids was investigated in HepG2 cell. It was found that the acacetin, diosmetin and rutin dose-dependently enhanced LDL uptake in HepG2 cells comparing to control. Furthermore, in a hyperlipidemia C57BL/6J mice model, administration of acacetin, diosmetin and rutin (30 mg/kg/d, intragastric, for three weeks) significantly decreased the levels of total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) in plasma, respectively. Overall, these findings indicated the potential of FCAVA in the development of functional food or medicine for the prevention and treatment of hyperlipidemia, which could be considered for the improvement of quality standardization of FCAVA.

Ten directions for improving clinical therapeutic effect of pancreatic cancer in the future / 中华外科杂志

Pancreatic cancer is one of the most malignant digestive system tumors. In the recent decade, the effect of diagnosis and treatment of pancreatic cancer has improved due to the renewal of treatment concept and the popularization of effective treatment. However, the overall efficacy of pancreatic cancer is still dismal and the 5-year survival rate is only about 10%. Further improving the diagnosis and treatment of pancreatic cancer is the top priority of oncology research and clinical practice. Based on past clinical and scientific research experience, the authors have proposed ten hot spots and future directions for a reference, which focusing on early prevention, early diagnosis, and early treatment of pancreatic cancer, molecular typing and precise treatment, new drug development and regimen combination, surgical technology and strategy change, model establishment and database development, as well as innovation of traditional Chinese medicine and breakthrough of treatment concept. A breakthrough in the diagnosis and treatment of pancreatic cancer in the next ten years is raising hope, when doctors can truly prevent and control pancreatic cancer.

External treatment of traditional Chinese medicine for constipation after thoracolumbar compression fractures: A protocol for systematic review and meta-analysis.

BACKGROUND: Constipation is one of the common complications of thoracolumbar compression fractures, which seriously affects the quality of life and increases pain of patients. External treatment of traditional Chinese medicine (TCM) has been widely used clinically for constipation after thoracolumbar compression fractures, but there are no systematic review and meta-analysis of its efficacy. Therefore, we will conduct this study to systematically evaluate the clinical effects of external treatment of TCM for patients with constipation after thoracolumbar compression fractures. METHODS: We will search the following electronic databases: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infastructure, Chinese Biomedical Literatures Database, Chinese Scientific Journal Database, and Wanfang Database. Randomized controlled trials on the treatment of constipation after thoracolumbar compression fractures with external treatment of TCM published from inception to May 2021 will be included in the search scope. The observation group was treated with Simple external treatment of TCM (such as external application of Chinese medicine, Chinese drugs at the acupoint, acupuncture, moxibustion, etc) or external treatment of TCM combined with conventional treatment/nursing of Western medicine, while the control group only was treated by conventional treatment/nursing of Western medicine. After screening literatures, extracting data, and assessing the risk of bias in the included studies, meta-analysis will be performed by Revman 5.3 software. RESULTS: This study is expected to provide an evidence of the efficacy of external treatment of TCM for constipation after thoracolumbar compression fractures. CONCLUSION: The results of this meta-analysis may help provide evidence to determine whether external treatment of TCM can be effective interventions for thoracolumbar compression fractures patients with constipation. TRIAL REGISTRATION NUMBER: INPLASY202150005.

Quassinoids from Brucea javanica and attenuates lipopolysaccharide-induced acute lung injury by inhibiting PI3K/Akt/NF-κB pathways.

Four new quassinoids (1-4) and twenty known analogues (5-24) were isolated from the seeds of Brucea javanica. All the compounds belong to tetracyclic quassinoids. The structures of the new compounds were elucidated by comprehensive spectroscopic analysis, including HRESIMS and 1D, 2D NMR. In in vitro bioassays, (5-9, 17-19 and 23) showed inhibitory activities for nitric oxide (NO) release in LPS-activated MH-S macrophages and IC50 values of 0.11-45.56 µM. Among them, bruceoside B significantly decreased LPS-induced NO, secretion of inflammatory factor cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß). Western Blot was used to verify the expression of p-IκB-α, IκB-α, p-NF-κB, NF-κB, Bax, Bcl-2, Caspase-3, p-PI3K, PI3K, p-Akt, and Akt proteins in PI3K/Akt/NF-κB signal pathway. Bruceoside B inhibited the activity of Akt and its downstream pathways and reduced the activation of apoptotic. In vivo, it was found that bruceoside B had obvious therapeutic effect on LPS-induced acute lung injury (ALI) in mice, and the effect of tissue section was obvious. The regulatory signal pathway of bruceoside B on inflammation was consistent with the anti-inflammatory pathway in vitro. Therefore, the results implied that bruceoside B has a certain therapeutic effect on inflammation and has a certainly effect on acute lung injury.

[Main chemical constituents in aerial parts of Glycyrrhiza uralensis by UPLC-Q-Exactive Orbitrap-MS].

Chemical constituents from aerial parts of Glycyrrhiza uralensis were analyzed and identified using ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS). The chromatographic column of Waters Acquity UPLC BEH-C_(18)(2.1 mm×100 mm, 1.7 µm) was adopted, with acetonitrile-water(0.5% formic acid) as mobile phase at a flow rate of 0.2 mL·min~(-1). Data was collected in positive and negative modes of electrospray ionization(ESI). A total of 55 compounds, including 42 flavonoids, 9 stilbenes, 2 coumarins, 1 lignin and 1 phenolic acid, which were characterized in the aerial parts of G. uralensis based on accurate molecular mass information of molecular and product ions provided by UPLC-Q-Exactive Orbitrap-MS based on comparison with standard substances and references. It is an effective and accurate method to provide chemical information of constituents in aerial parts of G. uralensis, and can provide a reference for further study on pharmacodynamic material basis and resources development and utilization.

Comprehensive chemical and metabolic profiling of anti-hyperglycemic active fraction from Clerodendranthi Spicati Herba.

Extensive pharmacological research has demonstrated that Clerodendranthi Spicati Herba has an obvious anti-hyperglycemic effect via α-glucosidase inhibitory activity. However, the anti-hyperglycemic active fraction and its metabolic behavior in vivo have not been elaborated clearly. In this study, ultra-high-performance liquid chromatography coupled to quadrupole time of flight tandem mass spectrometry with data filtering strategy, including mass defect screening, diagnostic product ions and neutral loss identification, was established for chemical and metabolic profiling of anti-hyperglycemic active fraction from Clerodendranthi Spicati Herba. A total of 28 methoxylated flavonoids and 61 diterpenoids were rapidly identified. Four main known methoxylated flavonoids were purified and unambiguously identified by nuclear magnetic resonance analysis. Thirty-one absorbed diterpenoids, 12 absorbed methoxylated flavonoids, and 56 methoxylated flavonoids metabolites were identified in rat plasma, urine, bile, and feces after oral administration of anti-hyperglycemic active fraction. The methoxylated flavonoids were predominantly metabolized by demethylation, sulfation, and glucuronidation. Glucuronidation metabolites found in bile and urine after demethylation were dominant metabolites. Diterpenoids were absorbed into the blood mainly in the form of prototypes and excreted through bile and urine. These results indicated that methoxylated flavonoids and diterpenoids were responsible for α-glucosidase inhibitory activity, which might provide novel drug candidates for the management of diabetes mellitus.

Acupuncture for diabetic neurogenic bladder: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic neurogenic bladder (DNB) is one of the common complications of diabetes mellitus, which has a high prevalence rate. Some research suggested that acupuncture can improve the clinical symptoms of diabetic neurogenic bladder patients, but there is no systematic review or meta-analysis to assess this therapy. Therefore, this study aims to explore the effectiveness and safety of acupuncture for patients with DNB. METHODS: In this study, we will search for electronic databases including the Cochrane Library, Web of Science, PubMed, MEDLINE, EMBASE,China National Knowledge Infrastructure (CNKI), Wan-Fang, and Baidu Scholar Database from inception to December 2020. We will select randomized controlled trials that have been published in English or Chinese related to acupuncture for DNB. Selection of study, extraction of data, and assessment of study quality will be performed independently by 2 researchers, and we will use Revman 5.3 software which is provided by Cochrane assistance network, to perform the data analysis. RESULTS: This study will provide evidence of the effectiveness and safety of acupuncture for DNB. CONCLUSION: This study will clarify whether acupuncture is an effective treatment for DNB, and will also provide a reference for clinical practice and guidelines development.

Gramicidin-S-Inspired Cyclopeptidomimetics as Potent Membrane-Active Bactericidal Agents with Therapeutic Potential.

Antimicrobial peptides (AMPs) are promising antibacterial agents often hindered by their undesired hemolytic activity. Inspired by gramicidin S (GS), a well-known cyclodecapeptide, we synthesized a panel of antibacterial cyclopeptidomimetics using ß,γ-diamino acids (ß,γ-DiAAs). We observed that peptidomimetic CP-2 displays a bactericidal activity similar to that of GS while possessing lower side-effects. Moreover, extensive studies revealed that CP-2 likely kills bacteria through membrane disruption. Altogether, CP-2 is a promising membrane-active antibiotic with therapeutic potential.

Main chemical constituents in aerial parts of Glycyrrhiza uralensis by UPLC-Q-Exactive Orbitrap-MS / 中国中药杂志

Chemical constituents from aerial parts of Glycyrrhiza uralensis were analyzed and identified using ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS). The chromatographic column of Waters Acquity UPLC BEH-C_(18)(2.1 mm×100 mm, 1.7 μm) was adopted, with acetonitrile-water(0.5% formic acid) as mobile phase at a flow rate of 0.2 mL·min~(-1). Data was collected in positive and negative modes of electrospray ionization(ESI). A total of 55 compounds, including 42 flavonoids, 9 stilbenes, 2 coumarins, 1 lignin and 1 phenolic acid, which were characterized in the aerial parts of G. uralensis based on accurate molecular mass information of molecular and product ions provided by UPLC-Q-Exactive Orbitrap-MS based on comparison with standard substances and references. It is an effective and accurate method to provide chemical information of constituents in aerial parts of G. uralensis, and can provide a reference for further study on pharmacodynamic material basis and resources development and utilization.

[Restoration of River Sediment by Calcium Peroxide(CaO2) Combined with Biochar].

The internal source pollution of sediment is the main factor leading to the repetition of black-odorous river channels. In order to prevent this situation, a river channel in the Binhu District of Wuxi City was used as an experimental site. In-situ CaO2 combined with a biochar covering technology was used to repair the black odorous river sediment in this channel. The effects of this technology on the quality of mud water, sedimentary volatile sulfide (AVS) and phosphorus forms, microorganisms, and restoration of black odorous sediment were investigated. The results showed that CaO2 combined with biochar coverage could significantly increase the dissolved oxygen (DO) concentration and redox potential (ORP) of the muddy water system. The DO concentration and ORP in the overlying water were maintained above 2 mg·L-1 and 50 mV, respectively. The removal rates of interstitial water ammonia-nitrogen (NH4+-N), chemical oxygen demand (COD), and total phosphorus (TP) reached 43.40%, 41.18%, and 50.97%, respectively. The removal rate of AVS in the sediment reached 37.03%. The high-throughput sequencing showed that the relative abundance of anaerobic microorganisms in the sediment was significantly reduced, and that nitrogen and sulfur removal microorganisms appeared (e.g., Thermomonas, Dechloromonas, Proteus hauser, Desulfomicrobium, and Thiobacillus). Phosphorus in the sediment was converted into Fe/Al-P and Ca-P. Therefore, in-situ CaO2 combined with biochar coverage had a good repairing effect on black odorous sediment.

PL-S2, a homogeneous polysaccharide from Radix Puerariae lobatae, attenuates hyperlipidemia via farnesoid X receptor (FXR) pathway-modulated bile acid metabolism.

Polysaccharides are important active constituents of Radix Puerariae lobatae (RPL). In this study, a novel homogeneous polysaccharide from RPL was successfully obtained by HP-20 macroporous resin and purified by Sepharose G-100 column chromatography. Nuclear magnetic resonance (NMR) analysis showed that the main glycosidic bonds were composed of α-1,3-linked and α-1,4-linked glucose. The molecular weight of PL-S2 was 18.73 kDa. The hypolipidemic effect of PL-S2 on hyperlipidemic rats was evaluated in histopathology and metabolomics analyses. PL-S2 significantly reduced plasma lipid levels and inhibited bile acid metabolism. We also demonstrated that treatment with PL-S2 activated FXR, CYP7A1, BESP, and MRP2 in rat liver. Our findings first indicate that PL-S2 decreases plasma lipid levels in hyperlipidemic rats by activating the FXR signaling pathway and promoting bile acid excretion. Therefore, PL-S2 derived from RPL is implicated as a functional food factor with lipid-regulating activity, and highlighted as a potential food supplement for the treatment of hyperlipidemia.

Active surveillance in metastatic pancreatic neuroendocrine tumors: A 20-year single-institutional experience.

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) are heterogeneous and indolent; systemic therapy is not essential for every patient with metastatic PanNET. The National Comprehensive Cancer Network guidelines state that delaying treatment is an option for PanNET with distant metastasis, if the patient has stable disease. However, specific factors that influence surveillance were not mentioned. In addition, data regarding the period of active surveillance in patients with metastatic PanNET are lacking. AIM: To specifically determine factors influencing active surveillance in patients with liver metastatic nonfunctioning PanNETs (NF-PanNETs). METHODS: Seventy-six patients with liver metastatic NF-PanNETs who received active surveillance from a high-volume institution were enrolled. Time to disease progression (TTP) and time to initiation of systemic therapy were determined. RESULTS: Thirty-one (40.8%) patients had recurrent liver disease after R0 resection; 45 (59.2%) were diagnosed with liver metastasis. The median follow-up period was 42 mo and 90.7% patients were observed to have disease progression. The median TTP (mTTP) was 10 mo. Multivariate analysis showed that the largest axis of the liver metastasis > 5 mm (P = 0.04), non-resection of the primary tumor (P = 0.024), and T3-4 stage (P = 0.028) were associated with a shorter TTP. The mTTP in patients with no risk factors was 24 mo, which was significantly longer than that in patients with one (10 mo) or more (6 mo) risk factors (P < 0.001). A nomogram with three risk factors showed reasonable calibration, with a C-index of 0.603 (95% confidence interval: 0.47-0.74). CONCLUSION: Active surveillance may only be safe for metastatic NF-PanNET patients with favorable risk factors, and other patients progressed rapidly without treatment. Further studies with a larger sample size and a control group are needed.

Structural characterization of a homopolysaccharide with hypoglycemic activity from the roots of Pueraria lobata.

A water-soluble neutral homopolysaccharide (PLP-1) was obtained from the roots of Pueraria lobata by DEAE cellulose and Sephadex G-200 gel chromatography purification. The average molecular weight of PLP-1 was 16.2 kDa. Monosaccharide composition analysis showed that PLP-1 was composed of glucose as a glucan. The structure of PLP-1 was characterized on the basis of extensive physical and chemical analysis, which indicated that the backbone of PLP-1 was mainly composed of →3)-α-d-Glcp(1→ and →4)-ß-d-Glcp(1→ with a molar ratio of 7.0 : 1.0. Moreover, the hypoglycemic activity of PLP-1 was investigated by palmitic acid and high glucose induced insulin resistant HepG2 cells. The results elucidated that PLP-1 could decrease the glucose concentration by up-regulating the expression of PI3K and AKT, and down-regulating the expression of FoxO1, PCK2, and G6Pase in insulin resistant cells. Therefore, PLP-1 could serve as a dietary supplement to ameliorate insulin resistance for diabetic patients.

[Study advances of microwave processing technology in traditional Chinese medicine].

The iterative innovation of processing technology is one of the important tasks in studies on processing of traditional Chinese medicine(TCM). It is also the prerequisite for modern, refined, automatic and intelligent manufacturing of TCM pieces. Microwave processing is a new fire processing technique developed in the recent 30 years, with a unique thermodynamic form, and energy transfer and transformation laws. Moreover, it owns the advantages of a high processing efficiency, good product properties and low production energy consumption, with great application prospects. This paper introduced the study overview of microwave expansion technology in the food industry, reviewed the origin of microwave processing technology of TCM, and expounded the basic concept, principle and main purpose of microwave processing technology used in TCM. Then, the impacts of drug factors and microwave factors on the microwave processing effect were summarized, the industrial equipment that could be used for microwave processing was listed, and the impacts of microwave heating on starch, polysaccharide, protein and other components in Chinese herbal medicines were analyzed. Furthermore, the study advance of microwave processing of 14 herbs was investigated, including Aconiti Lateralis Radix Praeparaia, Galli Gigerii Endothelium Corneum and Asini Corii Colla; and the appearance and components of herbs processed by traditional processing method and microwave processing method were compared, so as to reveal the opportunities and challenges of microwave processing technology in the industrial transformation. We hoped that the systematic study of microwave processing technology could provide new ideas and techniques for the high-quality and high-level development of the TCM pieces industry in the new era, and promote its inheritance, innovation and transformation.

Colonic transendoscopic tube-delivered enteral therapy (with video): a prospective study.

BACKGROUND: Colonic transendoscopic enteral tubing (TET) refers to colonic transendoscopic tube-delivered enteral therapy. Colonic TET has been successfully used for frequent colonic administration of drugs or multiple fecal microbiota transplantations (FMTs). This prospective observational study aimed to evaluate possible factors affecting methodology, feasibility and safety of colonic TET. METHODS: Patients who underwent colonic TET at our center from October 2014 to November 2018 were included. The feasibility, efficacy, and safety of TET were evaluated. RESULTS: In total, 224 patients were analyzed. The success rate of TET was 100%. The median retention time of TET tube within the colonic lumen was 8.5 (IQR 7-11) days in 158 patients with tube falling out spontaneously, and the maximum retention time was up to 28 days. These patients were divided into the short-retention group (≤ 8.5 days) and the long-retention group (> 8.5 days). Univariate and multivariate analysis demonstrated that the type of endoscopic clip (p = 0.001) was an independent factor for the retention time. The larger clips as well as a greater number of clips significantly affected the retention time (p = 0.013). No severe adverse event was observed during and after TET. CONCLUSIONS: Colonic TET is a feasible, practical, and safe colon-targeted drug delivery technique with a high degree of patients' satisfaction. Two to four large endoscopic clips are recommended to maintain stability of the TET tube within the colon for over 7 days.

A randomized, multicenter and noninferiority study of amoxicillin plus berberine vs tetracycline plus furazolidone in quadruple therapy for Helicobacter pylori rescue treatment.

OBJECTIVE: Helicobacter pylori (H. pylori) infection is closely associated with gastric ulcers and gastric adenocarcinomas. We aimed to assess the efficacy and safety of a quadruple regimen with amoxicillin plus berberine vs tetracycline plus furazolidone in rescue therapy for H. pylori eradication. METHODS: We conducted a randomized, open-label, multicenter, noninferiority trial. Patients with previous treatment failures recruited from five centers were randomized (1:1) to receive a regimen with esomeprazole and bismuth plus either berberine and amoxicillin (the BA group) or tetracycline and furazolidone (the TF group) for 14 days. Their H. pylori infection status was confirmed 4-8 weeks after treatment. The primary outcome was the eradication rate. The secondary outcomes included the rates of symptom improvement, compliance, and adverse events. This study was registered at ClinicalTrials.gov (NCT03609892). RESULTS: Altogether 658 participants were consecutively enrolled. An intention-to-treat analysis demonstrated that the two regimens achieved a similar eradication rate (76.3% vs 77.5%; P = 0.781). The per-protocol analysis reached a similar result (81.5% vs 85.0%; P = 0.278). The eradication rate reached in the BA group was greater than the pre-established margin of noninferiority, at -10% (the lower bounds of the 95% CI were -7.66% and -9.43%, respectively). The rate of adverse events was lower for the BA group than the TF group (18.5% vs 26.1%, P = 0.024). Rates of compliance and symptom improvement were similar for the two therapies. CONCLUSION: The efficacy of both regimens in rescue treatment for H. pylori eradication was satisfactory, 14-day BA-based quadruple therapy is noninferior to the TF-based therapy.