Efficacy of real-time artificial intelligence-aid endoscopic ultrasonography diagnostic system in discriminating gastrointestinal stromal tumors and leiomyomas: a multicenter diagnostic study.

Background: Gastrointestinal stromal tumors (GISTs) represent the most prevalent type of subepithelial lesions (SELs) with malignant potential. Current imaging tools struggle to differentiate GISTs from leiomyomas. This study aimed to create and assess a real-time artificial intelligence (AI) system using endoscopic ultrasonography (EUS) images to differentiate between GISTs and leiomyomas. Methods: The AI system underwent development and evaluation using EUS images from 5 endoscopic centers in China between January 2020 and August 2023. EUS images of 1101 participants with SELs were retrospectively collected for AI system development. A cohort of 241 participants with SELs was recruited for external AI system evaluation. Another cohort of 59 participants with SELs was prospectively enrolled to assess the real-time clinical application of the AI system. The AI system's performance was compared to that of endoscopists. This study is registered with Chictr.org.cn, Number ChiCT2000035787. Findings: The AI system displayed an area under the curve (AUC) of 0.948 (95% CI: 0.921-0.969) for discriminating GISTs and leiomyomas. The AI system's accuracy (ACC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) reached 91.7% (95% CI 87.5%-94.6%), 90.3% (95% CI 83.4%-94.5%), 93.0% (95% CI 87.2%-96.3%), 91.9% (95% CI 85.3%-95.7%), and 91.5% (95% CI 85.5%-95.2%), respectively. Moreover, the AI system exhibited excellent performance in diagnosing ≤20 mm SELs (ACC 93.5%, 95% CI 0.900-0.969). In a prospective real-time clinical application trial, the AI system achieved an AUC of 0.865 (95% CI 0.764-0.966) and 0.864 (95% CI 0.762-0.966) for GISTs and leiomyomas diagnosis, respectively, markedly surpassing endoscopists [AUC 0.698 (95% CI 0.562-0.834) for GISTs and AUC 0.695 (95% CI 0.546-0.825) for leiomyomas]. Interpretation: We successfully developed a real-time AI-assisted EUS diagnostic system. The incorporation of the real-time AI system during EUS examinations can assist endoscopists in rapidly and accurately differentiating various types of SELs in clinical practice, facilitating improved diagnostic and therapeutic decision-making. Funding: Science and Technology Commission Foundation of Shanghai Municipality, Science and Technology Commission Foundation of the Xuhui District, the Interdisciplinary Program of Shanghai Jiao Tong University and the Research Funds of Shanghai Sixth people's Hospital.

Expression and significance of pin1 in the wound healing.

The aim of this study is to delineate the expression patterns of prolyl cis-trans isomerase NIMA-interacting protein 1 (Pin1), Glial cell-derived neurotrophic factor (GDNF), and Angiotensin II (ANG II) during the process of wound repair, and to ascertain the effects of Pin1, GDNF, and ANG II on the healing of wounds in a rat model. A total of 18 rats were allocated into three groups-sham (control), DMSO (vehicle control), and Pin1 inhibitor (treatment with juglone)-with six animals in each group. An animal model of wound healing was established, followed by the intraperitoneal administration of juglone. Tissue samples from the wounds were subsequently collected for histopathological evaluation. Expression levels of Pin1, GDNF, and Ang II were quantified. In addition, an in vitro model of wound healing was created using human umbilical vein endothelial cells (HUVEC), to assess cell proliferation, migration, and tube formation under conditions of juglone pre-treatment. The expression levels of Pin1, GDNF, and ANG II were notably elevated on 7-, and 10- days post-wound compared to those measured on 3-day. Contrastingly, pre-treatment with juglone significantly inhibited the expression of these molecules. Histological analyses, including HE (Hematoxylin and Eosin), Masson's trichrome, and EVG (Elastic van Gieson) staining, demonstrated that vascular angiogenesis, as well as collagen and elastin deposition, were substantially reduced in the juglone pre-treated group when compared to the normal group. Further, immunohistochemical analysis revealed a considerable decrease in CD31 expression in the juglone pre-treatment group relative to the normal control group. Pin1 serves as a pivotal facilitator of wound repair. The findings indicate that the modulation of Pin1, GDNF, and ANG II expression impacts the wound healing process in rats, suggesting potential targets for therapeutic intervention in human wound repair.

[Effect and mechanism of free total rhubarb anthraquinones on pyroptosis of J774A.1 macrophages].

In this study, J774A.1 macrophages stimulated by lipopolysaccharide(LPS) and adenosine triphosphate(ATP) were used to establish an in vitro model of pyroptosis, and the intervention mechanism of free total rhubarb anthraquinones(FTRAs) on pyroptosis was investigated. J774A.1 macrophages were cultured in vitro, and the experiment was assigned to the control group and groups with different concentrations of LPS(0.25, 0.5, and 1 µg·mL~(-1)) and ATP(1.25, 2.5, and 5 mmol·L~(-1)). An in vitro model of macrophage pyroptosis was established by detecting cell viability through CCK-8, propidium iodide(PI) apoptotic cell staining, lactate dehydrogenase(LDH), interleukin(IL)-18, and tumor necrosis factor(TNF)-α release. Then, J774A.1 macrophages were randomly divided into six groups: blank control group, LPS+ATP group, high-dose FTRA group, and low, medium, and high-dose FTRA pre-protection group. The phenotypic characteristics and key indicators of pyroptosis were detected as the basis for evaluating the effect of FTRAs on pyroptosis induced by LPS and ATP. Western blot and RT-PCR were used to detect the expression levels of protein and mRNA related to the pyroptosis pathway in caspase-1/11 and elucidate the molecular mechanism of the anti-pyroptosis effect. The results showed that the stimulation condition of 0.50 µg·mL~(-1) LPS+5.00 mmol·L~(-1) ATP was the most effective in the in vitro model of macrophage pyroptosis. FTRAs pre-protected cells for 24 h and then can increase cell viability under pyroptosis conditions, alleviate cell damage, lower the positive rate of PI staining, and reduce the release of LDH, IL-18, and TNF-α. FTRAs were able to significantly inhibit the activation of GSDMD proteins and significantly down-regulate the protein expression of the pyroptosis pathway signature molecules, TLR4, NLRP3, cleaved-caspase-1, and cleaved-caspase-11, but they had no significant effect on ASC proteins. FTRAs were also able to significantly inhibit the mRNA expression of caspase-1, caspase-11, and GSDMD. These results indicate that FTRAs have an inhibitory effect on the pyroptosis model induced by LPS and ATP and play an anti-pyroptosis effect by regulating classical and non-classical pyroptosis signaling pathways and reducing the production of inflammatory cytokines.

Free total rhubarb anthraquinones protect intestinal mucosal barrier of SAP rats via inhibiting the NLRP3/caspase-1/GSDMD pyroptotic pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhubarb is the peeled and dried roots of Rheum palmatum L. and Rheum tanguticum Maxim. ex Balf. or Rheum officinale Baill. Free total rhubarb anthraquinones (FTRAs) were isolated and extracted from rhubarb. Previous studies have revealed that the early administration of FTRAs protects the intestinal mucosal barrier in rats with severe acute pancreatitis (SAP), the mechanism of which is not yet clear. However, we observed an enhanced expression of intestinal pyroptotic factors in rats treated with SAP, which may be related to the mechanism of intestinal barrier protection by FTRAs. AIM OF THE STUDY: The main objective of this study was to investigate the mechanism by which FTRAs protect the intestinal mucosal barrier in SAP rats, focusing on the classical pyroptosis pathway. MATERIALS AND METHODS: SAP was induced in rats through retrograde injection of sodium taurocholate via the pancreaticobiliary duct. Subsequently, FTRAs (22.5, 45, and 90 mg/kg), rhubarb (900 mg/kg, positive control), and saline (control) were administered at 0 h (immediately), 12 h, and 24 h post-surgery. Pancreatic and intestinal tissue injury, positive PI staining rate, and expression levels of various factors in intestinal tissues were compared across different groups. These factors include diamine oxidase (DAO), lactate dehydrogenase (LDH), high mobility group box chromosomal protein 1(HMGB1) and pro-inflammatory factors in intestinal and serum, pyroptosis-associated factors, toll-like receptor 4 (TLR-4), nuclear factor kappa-B (NF-kB), apoptosis-associated speck-like protein (ASC), NOD-like receptor protein 3 (NLRP3), cysteine protease-1 (caspase-1) and Gasdermin (GSDMD). RESULTS: The findings indicated that FTRAs protected the damaged intestine and pancreas and restored the expression of intestinal epithelial junction proteins in SAP rats. Additionally, it reduced intestinal and serum levels of DAO, interleukin 1, interleukin 18, HMGB1, and LDH, attenuated intestinal Positive PI staining rate, and significantly decreased the expressions of TLR-4, NF-kB, ASC, NLRP3, caspase-1 and GSDMD in SAP rats. CONCLUSIONS: The results suggest that FTRAs inhibited pyroptosis through down-regulation of the NLRP3-Caspase-1-GSDMD and TLR-4- NF-kB signaling pathways of intestinal tissues., thereby protecting the intestinal barrier of SAP rats.

Micro-biological degradation and transformation of dissolved organic matter following continuous cropping of tobacco.

In recent years, the problems associated with continuous cropping (CC) that cause soil degradation have become increasingly serious. As a key soil quality property, dissolved organic matter (DOM) affects the circulation of carbon and nutrients and the composition of bacterial communities in soil. However, research on the changes in the molecular composition of DOM after CC is limited. In this study, the soil chemical properties, DOM chemical diversity, bacterial community structure, and their interactions are explored in the soil samples from different CC years (CC1Y, CC3Y, CC5Y, and CC7Y) of tobacco. With increasing CC year of tobacco, most of the soil chemical properties, such as total carbon, total nitrogen and organic matter, decreased significantly, while dissolved organic carbon first decreased and then increased. Likewise, the trends of DOM composition differed with changing duration of CC, such as the tannin compounds decreased from 18.13 to 13.95%, aliphatic/proteins increased from 2.73 to 8.85%. After 7 years of CC, the soil preferentially produced compounds with either high H/C ratios (H/C > 1.5), including carbohydrates, lipids, and aliphatic/proteins, or low O/C ratios (O/C < 0.1), such as unsaturated hydrocarbons. Furthermore, core microorganisms, including Nocardioides, wb1-P19, Aquabacterium, Methylobacter, and Thiobacillus, were identified. Network analysis further indicated that in response to CC, Methylobacter and Thiobacillus were correlated with the microbial degradation and transformation of DOM. These findings will improve our understanding of the interactions between microbial community and DOM in continuous cropping soil.

Active DHEA uptake in the prostate gland correlates with aggressive prostate cancer.

Strategies for patient stratification and early intervention are required to improve clinical benefits for patients with prostate cancer. Here, we found that active DHEA utilization in the prostate gland correlated with tumor aggressiveness at early disease stages, and 3ßHSD1 inhibitors were promising for early intervention. [3H]-labeled DHEA consumption was traced in fresh prostatic biopsies ex vivo. Active DHEA utilization was more frequently found in patients with metastatic disease or therapy-resistant disease. Genetic and transcriptomic features associated with the potency of prostatic DHEA utilization were analyzed to generate clinically accessible approaches for patient stratification. UBE3D, by regulating 3ßHSD1 homeostasis, was discovered to be a regulator of patient metabolic heterogeneity. Equilin suppressed DHEA utilization and inhibited tumor growth as a potent 3ßHSD1 antagonist, providing a promising strategy for the early treatment of aggressive prostate cancer. Overall, our findings indicate that patients with active prostatic DHEA utilization might benefit from 3ßHSD1 inhibitors as early intervention.

Two-year outcomes of anti-reflux mucosectomy in treating gastroesophageal reflux disease: A Chinese prospective cohort study.

OBJECTIVES: Anti-reflux mucosectomy (ARMS) is an emerging and promising endoscopic treatment for gastroesophageal reflux disease (GERD). In the current study we aimed to evaluate the safety and efficacy of ARMS in treating Chinese GERD patients. METHODS: This was a single-center prospective cohort study. ARMS was performed in GERD patients by an experienced endoscopist. The patients were required to undergo symptom assessment as well as endoscopic examination, high-resolution manometry (HRM), and impedance-pH monitoring before and after ARMS. RESULTS: Twelve patients were enrolled. Follow-up was completed by all patients at 3 and 6 months, 11 patients at 1 year, and 8 patients at 2 years after ARMS, respectively. Symptom improvement was achieved in 66.7%, 75.0%, 72.7%, and 50.0% of the patients at 3 months, 6 months, 1 year, and 2 years after ARMS, respectively. Postoperative dysphagia was reported by 25.0%, 25.0%, 27.3%, and 25.0% of patients at 3 months, 6 months, 1 year, and 2 years after surgery, none of whom required additional invasive treatment. All patients with preoperative esophagitis healed after ARMS. For impedance-pH monitoring parameters, number of acidic reflux episodes and the proportion of patients with acid exposure time (AET) >4.0% decreased significantly after ARMS. CONCLUSIONS: ARMS was safe and effective in Chinese GERD patients. The efficacy of ARMS was not short-term and remained evident throughout the 2-year follow-up. Further multicenter studies with larger sample sizes are needed to verify our findings.

Approach1es for evolutionary, biochemical, and structural analysis of bacterial steroid 5α-reductases.

Steroid 5α-reductases (SRD5As), also known as 3-oxo-5α-steroid 4-dehydrogenases, are essential membrane-bound enzymes involved in steroid metabolism. Belonging to the NADPH-dependent oxidoreductase family, 5α-reductases catalyze steroids with 3-oxo-Δ4 structure, such as testosterone or progesterone, to produce their corresponding 3-oxo-5α steroids, which are necessary for a variety of physiological and pathological activities. Despite their significance, SRD5A structures are still in short supply to date. Here we describe a protocol for expression, purification, crystallization, structural determination, and functional analysis of PbSRD5A, the 5α-reductase from Proteobacteria bacterium sharing high sequence identity with human SRD5A1 and SRD5A2 isozymes, which we have recently structurally characterized using a lipidic cubic phase approach. Application of similar methods to other 5α-reductase isozymes will lead to breakthroughs in the understanding of the structure, function, and mechanism of oxidoreductases implicated in steroid metabolism.

Patients at risk for further examination with conventional gastroscopy after undergoing magnetically controlled capsule endoscopy.

OBJECTIVE: In this study we aimed to compare the need for further examination with conventional gastroscopy within 1 year after magnetically assisted capsule endoscopy (MCCE) examination between patients with gastrointestinal (GI) symptoms and asymptomatic individuals. METHODS: After propensity score matching analysis, 372 patients with GI symptoms and 372 asymptomatic individuals who had undergone MCCE at the First Affiliated Hospital of Sun Yat-sen University from January 1, 2019 to December 30, 2020 were retrospectively enrolled. Demographic and clinical characteristics of the participants and their MCCE and gastroscopic findings (performed within 1 year after MCCE) were analyzed. RESULTS: Fifty-one (6.85%) patients underwent further examination with conventional gastroscopy within 1 year after MCCE. Those with GI symptoms were more likely to undergo conventional gastroscopy than those without (9.95% vs 3.76%, P < 0.001). Polyps were the most common finding of MCCE. The rate of conventional gastroscopy in patients with focal lesions was significantly higher than that in those without focal lesions (P < 0.05). However, such rate did not differ in the different age groups (P = 0.106). CONCLUSIONS: MCCE is an optimal alternative for gastric examination, especially for large-scale screening of asymptomatic individuals. Patients with GI symptoms or focal lesions detected by MCCE are more likely to seek further examination with conventional gastroscopy for biopsy or endoscopic treatment than those without.

Overexpression of RAB31 in gastric cancer is associated with released exosomes and increased tumor cell invasion and metastasis.

BACKGROUND: Gastric cancer (GC) is one of most common cancers worldwide. Several studies have suggested that Rab31 functions as a membrane vesicle transport regulator; however, the mechanism by which RAB31 regulates exosome secretion and promotes metastasis remains to be clarified. METHODS: We examined the expression of RAB31 protein and mRNA in GC tissue samples via immunohistochemistry and reverse transcription-polymerase chain reaction assays, respectively. We elucidated the function of RAB31 in GC cells by constructing a cell model and a pulmonary metastatic model of GC with overexpression of RAB31. Protein mass spectrometry was used to identify the exosomal protein. RESULTS: RAB31 expression increased at both the protein and mRNA levels with the development of GC. Cells overexpressing RAB31 showed an enhanced ability to migrate in both the in vitro cell model and the pulmonary metastatic model of GC. Exosome nanoparticle tracking analysis and electron microscopy revealed that the both the number and size of the exosomes secreted by GC cells were reduced when RAB31 expression was depleted. Injection of exosomes derived from RAB31 overexpressing cells promoted pulmonary metastasis in vivo. Analysis of the exosomal proteins revealed that PSMA1 was overexpressed in GC tissue in accordance with RAB31 expression. PSMA1 overexpression was highly associated with poor prognosis of GC patients. CONCLUSION: Our findings revealed a key role for RAB31 in GC metastasis through regulation of exosome secretion.

Optimal timing of free total rhubarb anthraquinones on immune regulation in rats with severe acute pancreatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhubarb is the peeled and dried root of Rheum palmatum L., Rheum tanguticum Maxim. ex Balf. or Rheum officinale Baill. Free total rhubarb anthraquinones (FTRAs) isolated and extracted from rhubarb display the beneficial effects of anti-inflammation and immunological modulation. The timing of immune regulation is a major problem in the immunotherapy for severe acute pancreatitis (SAP). several studies reported that FTRAs could reduce systemic inflammatory responses by inhibiting early immune overactivity in the gut in rats with SAP. But, the optimal timing of rhubarb and FTRAs administration is not clear in clinical practice. Therefore, the time window for the best efficacy of rhubarb and FTRAs in the treatment of SAP patients should be further elucidated. AIM OF THE STUDY: The main purpose of the present study was to evaluate the efficacy and optimal timing of immune modulation with FTRAs in the treatment of SAP in rats. MATERIALS AND METHODS: FTRAs (22.5, 45 and 90 mg/kg), Rhubarb (RHU) (900 mg/kg, positive control) or normal saline (vehicle control) were initiated at 0 (immediately), 48 and 72 h every 12 h for three times in total. The therapeutic effects of FTRAs and RHU on pancreas and intestinal tissues injury, secondary infection with pseudomonas aeruginosa (PA), amylase, lipase, D-lactic acid (DLA), endotoxin (ET), proinflammatory and anti-inflammatory cytokines, macrophages, dendritic cells and regulatory T cells (Tregs) in the blood, small intestine and/or mesenteric lymph node (MLN) were determined in rats with SAP after treatment. RESULTS: The results showed that administration of FTRAs at 0 h was superior to 48 h and 72 h, which significantly protected the injury of pancreas and intestinal tissues, reduced the mortality induced by secondary infection with PA, decreased the levels of amylase, lipase, DLA, ET, tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), IL-6, IL-8, IL-18 and Tregs, and increased the levels of IL-4, sTNF-αR, macrophages and dendritic cells, secretary immunoglobulin A (SIgA) in the blood and/or small intestinal tissues in rats with SAP. CONCLUSIONS: In conclusion, our studies indicate that the treatment window of FTRAs for SAP is within 48 h of development, administration of FTRAs at the early stage (0 h, immune overreaction period) was the optimal time and superior to that of 48 h and 72 h for its therapeutic efficacy. The earlier the administration of FTRAs, the better the therapeutic efficacy. Therefore, our data may provide a scientific rationale for the clinical application and optimal timing of FTRAs in the treatment of SAP.

Prospective role of 3ßHSD1 in prostate cancer precision medicine.

BACKGROUND: Prostate cancer is addicted to androgens. The steroidogenic enzyme 3ß-hydroxysteroid dehydrogenase 1 (3ßHSD1) recognizes pregnenolone, dehydroepiandrosterone (DHEA), and steroidal medicine abiraterone as substrates to accelerate disease progression. METHODS: References for this review were identified through searches of PubMed with the search terms "prostate cancer", "HSD3B1", and "3bHSD1" from 1990 until June, 2022. RESULTS: Genotype of 3ßHSD1 has been reported to correlate with tumor aggressiveness of advanced prostate cancer in multiple clinical scenarios. The ethnic differences and limitations of using 3ßHSD1 genotype as a prognostic biomarker have been discussed here. The activity of 3ßHSD1 increases in patients treated with abiraterone and enzalutamide, giving rise to treatment resistance. Further elucidation of 3ßHSD1 regulatory mechanisms will shed light on more approaches for disease intervention. We also review the recent advance on 3ßHSD1 inhibitors and targeting 3ßHSD1 for prostate cancer management. Novel 3ßHSD1 inhibitors will be needed to provide additional options for prostate cancer management. CONCLUSION: 3ßHSD1 is both a predictive biomarker and a promising therapeutic target for prostate cancer.

Management of prostate cancer by targeting 3ßHSD1 after enzalutamide and abiraterone treatment.

Novel strategies for prostate cancer therapy are required to overcome resistance to abiraterone and enzalutamide. Here, we show that increasing 3ßHSD1 after abiraterone and enzalutamide treatment is essential for drug resistance, and biochanin A (BCA), as an inhibitor of 3ßHSD1, overcomes drug resistance. 3ßHSD1 activity increases in cell lines, biopsy samples, and patients after long-term treatment with enzalutamide or abiraterone. Enhanced steroidogenesis, mediated by 3ßHSD1, is sufficient to impair enzalutamide function. In patients, accelerated abiraterone metabolism results in a decline of plasma abiraterone as disease progresses. BCA inhibits 3ßHSD1 and suppresses prostate cancer development alone or together with abiraterone and enzalutamide. Daidzein, a BCA analog of dietary origin, is associated with higher plasma abiraterone concentrations and prevented prostate-specific antigen (PSA) increases in abiraterone-resistant patients. Overall, our results show that 3ßHSD1 is a promising target to overcome drug resistance, and BCA suppresses disease progression as a 3ßHSD1 inhibitor even after abiraterone and enzalutamide resistance.

Inhibiting 3ßHSD1 to eliminate the oncogenic effects of progesterone in prostate cancer.

Prostate cancer continuously progresses following deprivation of circulating androgens originating from the testis and adrenal glands, indicating the existence of oncometabolites beyond androgens. In this study, mass-spectrometry-based screening of clinical specimens and a retrospective analysis on the clinical data of prostate cancer patients indicate the potential oncogenic effects of progesterone in patients. High doses of progesterone activate canonical and non-canonical androgen receptor (AR) target genes. Physiological levels of progesterone facilitate cell proliferation via GATA2. Inhibitors of 3ß-hydroxysteroid dehydrogenase 1 (3ßHSD1) has been discovered and shown to suppress the generation of progesterone, eliminating its transient and accumulating oncogenic effects. An increase in progesterone is associated with poor clinical outcomes in patients and may be used as a predictive biomarker. Overall, we demonstrate that progesterone acts as an oncogenic hormone in prostate cancer, and strategies to eliminate its oncogenic effects may benefit prostate cancer patients.

Gypenosides Prevent and Dissolve Cholesterol Gallstones by Modulating the Homeostasis of Cholesterol and Bile Acids.

Gypenosides (GPs), obtained from Gynostemma pentaphyllum (Thunb.) Makino, have been traditionally prescribed to treat metabolic disorders in Asians. This study assessed whether GPs could prevent lithogenic diet (LD)-induced cholesterol gallstone (CG) formation and enhance CG dissolution in mice. Gallstone-susceptible C57BL/6J mice were fed an LD or normal chow, with or without GPs. Bile acids (BAs) in gallbladder bile were analyzed by liquid chromatography-tandem mass spectrometry. Differentially expressed hepatic genes were identified by RNA sequencing, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. GPs were found to prevent LD-induced CG formation and to dissolve pre-existing LD-induced CGs. GPs reduced total cholesterol levels and increased BA levels in bile, as well as reducing the BA Hydrophobicity Index, ratio of 12α-hydroxylated (12α-OH) to non-12α-OH BAs, and Cholesterol Saturation Index in gallbladder bile. GO and KEGG pathway enrichment analyses indicated that GPs-induced genes were involved in BA biosynthesis and cholesterol metabolism. GPs increased the hepatic expression of genes encoding the cytochrome P450 (Cyp) enzymes Cyp7a1, Cyp7b1, and Cyp8b1, while decreasing the hepatic expression of genes encoding the adenosine triphosphate-binding cassette (Abc) transporters Abcg5 and Abcg8. GPs may be a promising strategy for preventing and dissolving CGs.

Clinical practice guideline for transurethral plasmakinetic resection of prostate for benign prostatic hyperplasia (2021 Edition).

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline "2018 Standard Edition". However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons' surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons' skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.

Disease burden of primary gallbladder and biliary tract cancers associated with body mass index in 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017.

OBJECTIVE: To investigate the incidence of primary gallbladder and biliary tract cancer, mortality and disability-adjusted life years (DALY) of the global burden from 1990 to 2017. METHODS: Data of 195 countries and territories from 1990 to 2017 were extracted from the Global Health Data Exchange. The age-standardized incidence rate (ASIR) and estimated annual percentage change (EAPC) were employed to quantify trends in the incidence of primary gallbladder and biliary tract cancer. The age-standardized death rate (ASDR), age-standardized DALY and their corresponding EAPC were used to evaluate mortality trends. RESULTS: The global incidence of primary gallbladder and biliary tract cancer rose by 75.9% from 119 900 cases in 1990 to 210 900 cases in 2017. The highest ASIR was observed in Chile (10.8 per 100 000 in 2017), followed by Japan and South Korea. Regions with the highest social development index (SDI) quintile also had the highest death cases associated with primary gallbladder and biliary tract cancer in 2017 (60 100, 95% UI 55 800-62 700). A high body mass index (BMI) was found to be closely related to age-standardized deaths and age-standardized DALY in most of the regions analyzed. CONCLUSIONS: Primary gallbladder and biliary tract cancer remains a serious threat to global public health, especially in high-SDI countries. The ASDR and age-standardized DALY decreased from 1990 to 2017. A high BMI may be associated with this cancer burden.

ILF3-AS1 promotes the aerobic glycolysis and proliferation of melanoma cells by regulating miR-493-5p/PDK1 pathway.

BACKGROUND: The aim of this study was to investigate the role of ILF3-AS1 in regulating the survival of melanoma and its molecular mechanism. METHODS: The relative expression level of ILF3-AS1 in melanoma was assessed by qPCR. The effect of ILF3-AS1 and PDK1 on the cell viability was tested by MTT assay. Glucose uptake colorimetric assay, lactate assay, the measurements of extracellular acidification rate (ECAR) and Oxygen consumption rate (OCR) were performed to test the effect of ILF3-AS1 and PDK1 on the cellular glycolysis. Luciferase assay was conducted to detect the interactions of ILF3-AS1, miR-493-5p and PDK1. RNA immunoprecipitation chip (RIP) assay was used to detect the enrichments of ILF3-AS1 and miR-493-5p in the complex. Protein level of PDK1 was detected by western blot analysis. RESULTS: qPCR revealed that ILF3-AS1 was upregulated in human melanoma cell lines. MTT assay showed that ILF3-AS1 knockdown blunted cell proliferation, which was rescued by the overexpression of PDK1. Glucose uptake colorimetric assay, lactate assay, the measurements of ECAR and OCR indicated that ILF3-AS1 promoted glycolysis through PDK1. Western blotting results showed that ILF3-AS1 overexpression promoted PDK1 expression, which was prevented by miR-493-5p overexpression in SK-MEL-1 cells. CONCLUSIONS: ILF3-AS1 promotes the aerobic glycolysis and survival of melanoma cells involving miR-493-5p/PDK1 pathway.

[Analysis of curative effect of ultrasonic hyperthermia combined with TPF chemotherapy on 19 elderly with advanced oral squamous cell carcinoma].

PURPOSE: To evaluate the efficacy and safety of ultrasound hyperthermia combined with TPF chemotherapy for advanced oral squamous cell carcinoma in the elderly. METHODS: Nineteen elderly patients who had definite pathological diagnosis were enrolled in this clinical trail from June 2017 to January 2020. Docetaxel (75 mg/m2) + cisplatin (75 mg/m2) were given on the 1st day , and 5,Fu (750 mg/m2) on the 1st to 5th day of the cycle. Five times of hyperthermia were performed in the course of chemotherapy, respectively on the l, 3, 5, 7 and 9 days after the beginning of chemotherapy. All patients received 2 cycles of thermo -chemotherapy. Statistical analysis was performed using SPSS 20.0 software package. Kaplan-Meire method was used to calculate survival rate. RESULTS: According to the efficacy evaluation standard for solid tumor (version 1.0), complete response (CR) was seen in 3 cases, partial response (PR) was seen in 10 cases, stable disease(SD) was seen in 5 cases，progressive disease(PD) was seen in 1 case. The overall responding rate was 68.4%. The median follow-up time was 36 months(8-48 months), and the 2-year overall survival rates were 63.2%. No serious adverse reactions were observed. CONCLUSIONS: Ultrasound hyperthermic therapy combined with chemotherapy has a synergistic anti-tumor effect on patients with advanced oral squamous cell carcinoma, which is safe and effective, and is worthy of becoming another choice of tumor treatment.

Magnetic sphincter augmentation in treating refractory gastroesophageal reflux disease: A systematic review and meta-analysis.

OBJECTIVE: In this systematic review and meta-analysis we aimed to determine the efficacy and safety of magnetic sphincter augmentation (MSA) in the management of refractory gastroesophageal reflux disease (rGERD). METHODS: Literature search was conducted in PubMed, the Cochrane Library, EMBASE, Web of Science, OpenGrey and ClincalTrials.gov for single-arm studies evaluating the efficacy and safety of MSA in rGERD or comparative studies with proton pump inhibitor (PPI) or laparoscopic Nissen fundoplication (LNF) serving as the control published until April 2020. Primary outcome was the rate of postoperative PPI use, and secondary outcomes included postoperative GERD-health-related quality of life (GERD-HRQL), normalization of acid exposure time (AET) and incidence of procedure-related adverse events (AE). RESULTS: Ten single-arm studies, one randomized controlled trial and three cohort studies involving 1138 participants were included. Post-MSA PPI withdrawal, significant GERD-HRQL improvement and AET normalization were achieved in 87.0%, 88.0% and 75.0% of the patients, respectively. The incidence of postoperative dysphagia was 29% and endoscopic dilation was required in 7.4% of patients undergoing MSA. MSA showed a better efficacy in symptom control than PPI (PPI cessation: 91% vs 0%; GERD-HRQL improvement: 81% vs 8%) and similar effectiveness but a lower risk of gas-bloat syndrome (risk ratio [RR] 0.69, 95% confidence interval [CI] 0.51-0.93, P = 0.01) and better reserved ability to belch (RR 1.48, 95% CI 0.76-2.86, P = 0.25) compared with LNF. CONCLUSIONS: MSA was an effective and safe therapy for rGERD. Well-designed randomized trials that compare the efficacy of MSA with other therapies are needed.