Urinary metabolic profiles during Helicobacter pylori eradication in chronic gastritis.

BACKGROUND: Helicobacter pylori (H. pylori) infection is a major risk factor for chronic gastritis, affecting approximately half of the global population. H. pylori eradication is a popular treatment method for H. pylori-positive chronic gastritis, but its mechanism remains unclear. Urinary metabolomics has been used to elucidate the mechanisms of gastric disease treatment. However, no clinical study has been conducted on urinary metabolomics of chronic gastritis. AIM: To elucidate the urinary metabolic profiles during H. pylori eradication in patients with chronic gastritis. METHODS: We applied LC-MS-based metabolomics and network pharmacology to investigate the relationships between urinary metabolites and H. pylori-positive chronic gastritis via a clinical follow-up study. RESULTS: Our study revealed the different urinary metabolic profiles of H. pylori-positive chronic gastritis before and after H. pylori eradication. The metabolites regulated by H. pylori eradication therapy include cis-aconitic acid, isocitric acid, citric acid, L-tyrosine, L-phenylalanine, L-tryptophan, and hippuric acid, which were involved in four metabolic pathways: (1) Phenylalanine metabolism; (2) phenylalanine, tyrosine, and tryptophan biosynthesis; (3) citrate cycle; and (4) glyoxylate and dicarboxylate metabolism. Integrated metabolomics and network pharmacology revealed that MPO, COMT, TPO, TH, EPX, CMA1, DDC, TPH1, and LPO were the key proteins involved in the biological progress of H. pylori eradication in chronic gastritis. CONCLUSION: Our research provides a new perspective for exploring the significance of urinary metabolites in evaluating the treatment and prognosis of H. pylori-positive chronic gastritis patients.

Factors Associated with Intention to Use Telerehabilitation for Children with Special Needs: A Cross-Sectional Study.

Background: Children with special health care needs (CSHCN) require long-term and ongoing rehabilitation interventions supporting their development. Telerehabilitation can provide continuous rehabilitation services for CSHCN. However, few studies have explored the intention of CSHCN and their caregivers to use telerehabilitation and its impact on them. Objective: The objective of this study was to identify factors that influence the intention to use telerehabilitation among CSHCN and their caregivers. Methods: This study was a cross-sectional study. Based on the unified theory of acceptance and use of technology, extended with additional predictors (trust and perceived risk [PR]), this study developed a research model and proposed 10 hypotheses. A structured questionnaire was distributed to 176 caregivers. Data were analyzed and research hypotheses were tested using partial least squares structural equation modeling to better understand the factors influencing the use of telerehabilitation. Results: A total of 164 valid questionnaires were collected. CSHCN and their caregivers were overall satisfied with this telerehabilitation medical service. The results of the structural model analysis indicated that social influence (SI), facilitating conditions (FC), and trust had significant effects on behavioral intention (BI) to use telerehabilitation, while the paths between performance expectancy (PE), effort expectancy (EE), and PR and BI were not significant. PE, EE, and SI had a significant effect on trust. Moreover, EE and SI had indirect effects on BI, with trust as the mediator. Conclusions: The results indicated that SI, FC, and trust are significant factors influencing CSHCN and their caregivers' use of telerehabilitation. Trust is also an important mediator for the intention and highly influenced by PE, EE, and SI.

Eudesmane sesquiterpenoids with inhibitory effects on NO production from Artemisia princeps.

Five undescribed eudesmane methyl esters (1-5), three undescribed eudesmane-12,6-olides (6-8), and 21 known analogues (9-29) were isolated from the aerial part of Artemisia princeps Pamp. Their structures were established by detailed analysis of the NMR and HRESIMS data. The absolute configurations of 1-8 were determined based on single-crystal X-ray diffraction analysis and ECD calculations. Moreover, the inhibitory effects on LPS-induced NO production in BV-2 microglial cells of all the isolated compounds were assessed. Except for compounds 2, 4, 10, and 11, the others showed significant inhibitory activities, with IC50 values of 0.73-18.66 µM, wherein the potential structure-activity relationship was also discussed.

Hysterolides A-I, dimeric or monomeric sesquiterpene lactones from Parthenium hysterophorus L.

Nine undescribed sesquiterpene lactones, including two pseudoguaianolide dimers (1 and 2), a pseudoguaiac dilactone (3), and six pseudoguaianolides (4-9), along with 13 known analogues (10-22) were isolated from Parthenium hysterophorus. Among them, hysterolide A (1) possesses an unusual carbon skeleton with a unique cyclobutane ring connecting two pseudoguaianolides. Hysterolide C (3) is a sesquiterpene dilactone incorporating a bicyclo[5.1.0]octane core. Spectroscopic analyses, 13C NMR and ECD calculations, and X-ray diffraction elucidated their structures and absolute configurations. Moreover, all the isolates were assayed for their anti-inflammatory activities by inhibiting LPS-induced nitric oxide production in BV-2 microglia cells, wherein, nine compounds displayed significant inhibitory activities with IC50 of 0.52-6.32 µM. Furthermore, the preliminary structure-activity relationship was also established.

Malignant peripheral nerve sheath tumor with hemophilic syndrome and bone marrow fibrosis: A rare case report.

BACKGROUND: Malignant schwannoma is a rare tumor in the peripheral nervous system, accounting for approximately 5% to 10% of systemic soft tissue sarcomas. Especially, malignant schwannoma occurring in the broad ligament of the uterus with hemophilic syndrome and bone marrow fibrosis is extremely rare in clinical practice. Here, we report the first case of an patient diagnosed with malignant peripheral nerve sheath tumor (MPNST) of the broad ligament of the uterus with hemophilic syndrome and bone marrow fibrosis, and share our reference clinical diagnosis and treatment experience. CASE SUMMARY: A patient was diagnosed with MPNST of the uterus harboring hemophilic syndrome and bone marrow fibrosis. She received combination, and repeated imaging revealed further encountered rare complications (hemophilia syndrome and bone marrow fibrosis) after two cycles of chemotherapy. Thereafter, combined treatment with pazopanib, gemcitabine, and dacarbazine was initiated. Unfortunately, the patient succumbed to death at hospital after two weeks. CONCLUSION: This report firstly provided reference clinical practice for a patient with MPNST of the uterus harboring hemophilic syndrome and bone marrow fibrosis. Our case raises a reminder about the tolerance and safety of combination therapy, especially in young women.

[Ion Torrent PGM sequencing for detection of Y chromosome microdeletion in 87 cases of azoospermia].

OBJECTIVE: To explore the feasibility of Ion Torrent PGM sequencing in detection of Y chromosome microdeletion. METHODS: We enrolled 87 infertility patients with non-obstructive azoospermia (NOA) in this study and analyzed their routine semen parameters, reproductive hormone levels and chromosomal karyotypes. We detected Y chromosome microdeletion in the patients by Ion Torrent PGM sequencing and multiplex PCR, and compared the detection rates between the two methods. RESULTS: Ion Torrent PGM sequencing achieved a significantly higher detection rate of Y chromosome microdeletion than multiplex PCR (49.4% vs 12.6%, P < 0.05). The cases of AZF deletion detected by Ion Torrent PGM sequencing included all those detected by multiplex PCR, and the deletion sites were completely consistent. In addition, 14 male infertility-related gene mutations were detected in 24 of the 87 patients, with a total positive rate of 27.59%. CONCLUSION: Ion Torrent PGM sequencing can significantly improve the detection rate of Y chromosome microdeletion in infertility patients with NOA, detect a variety of male infertility-related gene mutations, and therefore contribute to the diagnosis of azoospermia.

Visible-Light-Induced Annulation of Iodonium Ylides and 2-Isocyanobiaryls to Access 6-Arylated Phenanthridines.

A 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4-CzIPN)-photocatalyzed cascade arylation/cyclization reaction of 2-isocyanobiaryls and iodonium ylides was established for the synthesis of 6-arylated phenanthridines. This is the first example of employing iodonium ylides as aryl radical sources in a visible-light-induced radical cascade cyclization reaction.

Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace.

OBJECTIVE: This study investigated trends in the study of phytochemical treatment of post-traumatic stress disorder (PTSD). METHODS: The Web of Science database (2007-2022) was searched using the search terms "phytochemicals" and "PTSD," and relevant literature was compiled. Network clustering co-occurrence analysis and qualitative narrative review were conducted. RESULTS: Three hundred and one articles were included in the analysis of published research, which has surged since 2015 with nearly half of all relevant articles coming from North America. The category is dominated by neuroscience and neurology, with two journals, Addictive Behaviors and Drug and Alcohol Dependence, publishing the greatest number of papers on these topics. Most studies focused on psychedelic intervention for PTSD. Three timelines show an "ebb and flow" phenomenon between "substance use/marijuana abuse" and "psychedelic medicine/medicinal cannabis." Other phytochemicals account for a small proportion of the research and focus on topics like neurosteroid turnover, serotonin levels, and brain-derived neurotrophic factor expression. CONCLUSION: Research on phytochemicals and PTSD is unevenly distributed across countries/regions, disciplines, and journals. Since 2015, the research paradigm shifted to constitute the mainstream of psychedelic research thus far, leading to the exploration of botanical active ingredients and molecular mechanisms. Other studies focus on anti-oxidative stress and anti-inflammation. Please cite this article as: Gao B, Qu YC, Cai MY, Zhang YY, Lu HT, Li HX, Tang YX, Shen H. Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace. J Integr Med. 2023; 21(4):385-396.

The clinicopathological characteristics of gastric cancer and precancerous conditions in gastric DLBCL and MALT lymphoma patients: a multi-center retrospective study.

OBJECTIVE: The objective of this study is to explore the clinicopathological characteristics of gastric cancer and precancerous conditions in patients with primary gastric lymphoma. METHODS: We analyzed 474 cases of primary gastric lymphoma, mainly DLBCL and MALT, from three clinical centres retrospectively, and compared the clinicopathological parameters of primary gastric lymphoma patients complicated with gastric cancer, precancerous conditions, or with no complications. RESULTS: A total of 5.1% of the patients with primary gastric lymphoma were diagnosed with gastric cancer, including metachronous gastric adenocarcinoma (3.2%) and synchronous gastric adenocarcinoma (1.9%). Of the patients with gastric lymphoma, 14.6% had precancerous conditions including atrophy (14.6%), intestinal metaplasia (8.9%), and low-grade intraepithelial neoplasia (1.9%). Primary gastric lymphoma patients with an ulcerative type (p = 0.009) and Lugano classification stage IIE + IV (p < 0.001) lymphoma had a higher risk of complicating with gastric cancers or precancerous conditions. The rate of infection of Helicobacter pylori (Hp) was 68.4% in patients with primary gastric lymphoma, which was higher in patients with MALT lymphoma (p < 0.001), Lugano classification stage I + II (p < 0.001), and patients complicated with precancerous conditions and gastric cancer (p < 0.001), especially gastric cancer of the intestinal type (p = 0.04). Gastric cancer (95.8%) and precancerous conditions (91.3%) occurred mostly in Hp-infected primary gastric lymphoma patients, with a minor subset of Hp-eradicated patients. Primary gastric lymphoma patients had a higher detection rate of early gastric cancer (25.0%) and a five-year survival rate (40.0%) than the general Chinese population. CONCLUSIONS: Patients with primary gastric lymphoma have a high risk of developing gastric cancer and precancerous conditions, and this risk may be related to Helicobacter pylori infection. Follow-up of primary gastric lymphoma provides an opportunity for the detection of early gastric cancer.Key messages5.1% of the patients with primary gastric lymphoma were diagnosed with gastric cancer.14.6% of the patients with gastric lymphoma had premalignant lesions including atrophy (14.6%), intestinal metaplasia (8.9%), and low-grade intraepithelial neoplasia (1.9%).Primary gastric lymphoma patients complicating with gastric cancer had a higher infection rate of Helicobacter pylori (100.0%), a detection rate of early gastric cancer (25.0%) and a five-year survival rate (40.0%) than the general Chinese population.

Neurobehavioral disorders induced by environmental zinc in female zebrafish (Danio rerio): Insights from brain and intestine transcriptional and metabolic signatures.

Human activities can cause zinc (Zn) contamination of aquatic environments. Zn is an essential trace metal, but effects of environmentally relevant Zn exposure on the brain-intestine axis in fish are poorly understood. Here, six-month-old female zebrafish (Danio rerio) were exposed to environmentally relevant Zn concentrations for six weeks. Zn significantly accumulated in the brain and intestine, causing anxiety-like behaviors and altered social behaviors. Zn accumulation altered levels of neurotransmitters, including serotonin, glutamate, and γ-aminobutyric acid, in the brain and intestine, and these changes were directly associated with changes in behavior. Zn caused oxidative damage and mitochondrial dysfunction, and impaired NADH dehydrogenase, thereby dysregulating the energy supply in brain. Zn exposure resulted in nucleotide imbalance and dysregulation of DNA replication and the cell cycle, potentially impairing the self-renewal of intestinal cells. Zn also disturbed carbohydrate and peptide metabolism in the intestine. These results indicate that chronic exposure to Zn at environmentally relevant concentrations dysregulates the bidirectional interaction of the brain-intestine axis with respect to neurotransmitters, nutrients, and nucleotide metabolites, thereby causing neurological disorder-like behaviors. Our study highlights the necessity to evaluate the negative impacts of chronic environmentally relevant Zn exposure on the health of humans and aquatic animals.

Choline and trimethylamine N-oxide supplementation in normal chow diet and western diet promotes the development of atherosclerosis in Apoe -/- mice through different mechanisms.

Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite, has been shown to aggravate cardiovascular disease. However, the mechanisms of TMAO in the setting of cardiovascular disease progress remain unclear. Here, we aim to investigate the effects of TMAO on atherosclerosis (AS) development and the underlying mechanisms. Apoe -/- mice received choline or TMAO supplementation in a normal diet and a western diet for 12 weeks. Choline or TMAO supplementation in both normal diet and western diet significantly promoted plaque progression in Apoe-/- mice. Besides, serum lipids levels and inflammation response in the aortic root were enhanced by choline or TMAO supplementation. In particular, choline or TMAO supplementation in the western diet changed intestinal microbiota composition and bile acid metabolism. Therefore, choline or TMAO supplementation may promote AS by modulating gut microbiota in mice fed with a western diet and by other mechanisms in mice given a normal diet, even choline or TMAO supplementation in a normal diet can promote AS.

Improving the Accuracy and Efficiency of Abnormal Cervical Squamous Cell Detection With Cytologist-in-the-Loop Artificial Intelligence.

Population-based cervical cytology screening techniques are demanding and laborious and have relatively poor diagnostic accuracy. In this study, we present a cytologist-in-the-loop artificial intelligence (CITL-AI) system to improve the accuracy and efficiency of abnormal cervical squamous cell detection in cervical cancer screening. The artificial intelligence (AI) system was developed using 8000 digitalized whole slide images, including 5713 negative and 2287 positive cases. External validation was performed using an independent, multicenter, real-world data set of 3514 women, who were screened for cervical cancer between 2021 and 2022. Each slide was assessed using the AI system, which generated risk scores. These scores were then used to optimize the triaging of true negative cases. The remaining slides were interpreted by cytologists who had varying degrees of experience and were categorized as either junior or senior specialists. Stand-alone AI had a sensitivity of 89.4% and a specificity of 66.4%. These data points were used to establish the lowest AI-based risk score (ie, 0.35) to optimize the triage configuration. A total of 1319 slides were triaged without missing any abnormal squamous cases. This also reduced the cytology workload by 37.5%. Reader analysis found CITL-AI had superior sensitivity and specificity compared with junior cytologists (81.6% vs 53.1% and 78.9% vs 66.2%, respectively; both with P < .001). For senior cytologists, CITL-AI specificity increased slightly from 89.9% to 91.5% (P = .029); however, sensitivity did not significantly increase (P = .450). Therefore, CITL-AI could reduce cytologists' workload by more than one-third while simultaneously improving diagnostic accuracy, especially compared with less experienced cytologists. This approach could improve the accuracy and efficiency of abnormal cervical squamous cell detection in cervical cancer screening programs worldwide.

[Systematic Evaluation of Low-carbon Operation of Typical A2O Processes in Municipal Sewage Plant].

Under the "Carbon Peak, Carbon Neutral" goal, the systematic evaluation of the carbon emission equivalent (CO2eq) and its compositions of the typical A2O process has important guiding significance for the low-carbon operation of most municipal sewage plants in China. Based on the operational data on the first municipal sewage plant of Jiaozuo in 2020 and the methods presented in "2019 Refinement to the 2006 IPCC Guidelines for National Greenhouse Gas Inventories, " a systematic evaluation of the CO2eq of the typical A2O process was established, including direct emissions that were built on the Arrhenius model introducing the water temperature factor and indirect emissions from the three aspects of electricity consumption, agent addition, and sludge transportation. The results showed that the daily emission intensities of CH4 and N2O were (115±56) kg·d-1 and (30±18) kg·d-1, respectively. Additionally, indirect carbon emissions from electricity consumption and agent addition accounted for 48.4% and 51.3% in the biochemical treatment section, respectively. In 2020, CO2eq amounts of total research plant and per unit sewage were 2.17×104 t and (0.63±0.07) kg·m-3, respectively. The magnitude of the proportion of different carbon emission compositions was as follows:sewage electricity (36.5%)>sewage agent (26.6%)>N2O direct (15.4%)>sludge agent (9.6%)>sludge electricity (6.7%)>CH4 direct (4.9%)>sludge transportation (0.3%). System import/export fluxes of carbon and nitrogen elements were calculated, followed by the carbon to nitrogen mass ratio in the sewage plant. Direct carbon emission characteristics of CH4 and N2O and their influencing factors were discussed, respectively. Based on the balance theory of carbon and nitrogen elements in the system, it is proposed that the selective introduction of industrial wastewater may become an important reference measure for the low-carbon operation of municipal sewage plants in the future.

Trends in prevalence and all-cause mortality of metabolic dysfunction-associated fatty liver disease among adults in the past three decades: Results from the NHANES study.

BACKGROUND: Given the escalating epidemic of obesity and diabetes coupled with redefined diagnostic criteria, it is critical to identify the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD). We sought to determine the prevalence and mortality outcomes of MAFLD subtypes based on diagnostic criteria in the USA over the past three decades. METHODS: Eleven cycles of the National Health and Nutrition Examination Surveys (NHANES; 1988-1994 and 1999-2020) were used, and 72,224 participants were included. MAFLD was defined according to the 2020 International Expert Consensus. Based on diagnostic criteria and risk factors, MAFLD was categorized into seven subtypes: type 1 (obesity subtype), 2 (metabolic unhealthy subtype), 3 (diabetes subtype), 4 (metabolic unhealthy non-diabetes subtype), 5 (obesity and diabetes subtype), 6 (metabolic unhealthy non-obesity subtype), and 7 (mixed subtype). RESULTS: Over the study period, the estimated prevalence of MAFLD increased significantly from 22% in 1988-1994 to 36% in 2017-2020. The prevalence of Type 4 was the highest, followed by that of Type 7, whereas other types were low and almost unchanged over time. Individuals with MAFLD had 19% and 38% increased mortality risks from all causes and cardiovascular disease, respectively. Among them, the metabolically unhealthy participants with normal weight demonstrated a 116% higher risk for all-cause mortality [hazard ratio (HR): 2.16, 95% CI: 1.52-3.08] and a 222% higher risk for cardiovascular mortality (HR: 3.22, 95% CI: 1.72-6.04). Interestingly, stratification and interaction analyses demonstrated a significant impact of metabolic parameters on the relationship between MAFLD and all-cause mortality. CONCLUSIONS: In conclusion, our study identified an increase in MAFLD prevalence and a significant association between metabolic derangements in MAFLD and all-cause or cardiovascular mortality.

Effect of 3-Dimensional Interstitial High-Dose-Rate Brachytherapy With Regional Metastatic Lymph Node Intensity-Modulated Radiation Therapy in Locally Advanced Peripheral Non-Small Cell Lung Cancer: 5-Year Follow-up of a Phase 2 Clinical Trial.

PURPOSE: We aimed to reveal the 5-year clinical outcomes of 3-dimensional (3D) interstitial high-dose-rate (HDR) brachytherapy with regional metastatic lymph node intensity modulated radiation therapy (IMRT) for locally advanced peripheral non-small cell lung cancer (NSCLC), which has been shown to have low toxicity and improved 2-year survival rates in patients with this disease. METHODS AND MATERIALS: In this phase 2, single-arm, open-label clinical trial, 83 patients with locally advanced peripheral NSCLC were enrolled (median follow-up [range], 53.7 [4.3-120.4] months). All eligible patients received 3D interstitial HDR brachytherapy with regional metastatic lymph node IMRT. The primary endpoint was overall survival (OS). Secondary endpoints were local recurrence-free survival, regional recurrence-free survival, progression-free survival, distant metastasis-free survival, toxicities, and quality of life. RESULTS: The final analysis included 75 patients (19 [25.3%] females, 56 [74.7%] males; median [range] age, 64 [44-80] years; stage IIIA, 34 [45.3%]; stage IIIB, 41 [54.7%]). At the latest follow-up, 32 (42.7%) patients had survived. The median OS was 38.0 months (5-year OS, 44.5%; 95% confidence interval [CI], 33.8%-58.6%). Local recurrence-free survival, recurrence-free survival, and distant metastasis-free survival at 5 years were 79.2% (95% CI, 68.5%-91.5%), 73.6% (95% CI, 61.5%-88.1%), and 50.3% (95% CI, 38.3%-66.1%), respectively. The dominant failure pattern was distant disease, corresponding to 40% (30 of 75) of patients and 65.2% (30 of 46) of all failures. Two (2.7%) patients developed grade 1 acute pneumonitis. Grade 2 and 3 acute esophagitis occurred in 11 (14.7%) and 4 (5.3%) patients, respectively. No late radiation-related grade ≥2 late adverse events were observed. CONCLUSIONS: 3D interstitial HDR brachytherapy with regional metastatic lymph node IMRT for locally advanced peripheral NSCLC shows significant OS and has a low toxicity rate. Additional evaluation in a phase 3 trial is recommended to substantiate these findings.

[Gonadoblastoma: Clinicopathological study and literature review of 3 cases].

OBJECTIVE: To investigate the clinical feature, pathological morphology, special histopathological subtype and immunohistochemical characteristic of gonadoblastoma. METHODS: Three patients of gonadoblastoma treated from 2014 to 2020 were enrolled, and the clinical characteristics, histological morphology and immunophenotype were analyzed, and the literatures were also reviewed. RESULT: Three phenotypical females were 14,17 and 27 years old. Case 1 was 46,XX with normal gonadal development. Case 2 was 46,XY and case 3 was chromosomal chimeric type (46, XY 90%/45,X 10%), both with dysgenetic gonads. Microscopically, the morphology of classic type was observed in all cases more or less, manifesting small nests of primitive germ cells and surrounding clustered sex cord-like cells, usually with Call-Exner like bodies and calcification. In additon, the morphology of special subtype can be seen in case 1,exhibiting cord-like tumor cells, which was segmentated by cellular fibrous stroma. Cases 2 and 3 were accompanied by dysgerminoma components. Immunohistochemically,all the primal germ cells were positive for OCT3/4, PLAP and CDll7 , and sexcord-like cells were positive for inhibin, SF-1, SOX9 and FOXL2 . Patients were followed up for 10 years, 6 years and 4 years respectively without recurrence. CONCLUSION: Gonadoblastoma is a rare germ cell-sex cord stromal tumor, which is usually accompanied by gonadal hypoplasia. As a special subtype, dissecting gonadoblastoma will be easily confused with dysgerminoma/seminoma, but the prognosis is better. So we should improve the understanding of this subtype and avoid overdiagnosis.

Three-target treatment combined with surgery for BRAF V600E-mutant colon cancer with peritoneal metastasis: a case report.

Background: BRAF V600E-mutant advanced colon cancer with peritoneal metastasis is associated with a poor prognosis. Surgery is not recommended by current guidelines, and there are few cases demonstrating the efficacy of targeted therapy combined with surgery in such patients. In the era of precision medicine, we apply aggressive surgery after successful conversion of triple-targeted drugs to prolong survival and provide a clinical basis for the treatment of such patients. Case Description: A 72-year-old male patient presented with abdominal distension and changes in bowel habits was admitted to the Department of Oncology, Shanxi Provincial People's Hospital. The patient was diagnosed with advanced ascending colon adenocarcinoma with peritoneal metastasis after relevant examinations such as abdominal enhanced computed tomography and tests of tumor markers. Later, further genetic testing was performed suggesting BRAF V600E mutation. We treated the patient with first-line three-target therapy (dabrafenib + trametinib + cetuximab). Repeat abdominal enhanced computed tomography after 6 weeks of three-target therapy revealed the disappearance of peritoneal metastases. Subsequently, after 3 months, the patient underwent resection of the primary lesion and removal of greater omental metastases. Three-target therapy continued after surgery until 4 months post-operation. However, carbohydrate antigen 199 was significantly increased at 9 months after medication discontinuation, and returned to normal after 4 months of re-initiation of three-target therapy. The three-target therapy was further adjusted to two-target therapy (dabrafenib + cetuximab) based on the results of circulating tumor cells, and the tumor markers are now normal. Conclusions: Patients with BRAF V600E colon cancer combined with peritoneal metastases are treated with targeted drug conversion therapy, and aggressive surgery may prolong survival depending on the conversion effect. Continued maintenance therapy after surgery may play a role in preventing recurrence.

Identification of DAPK1 as an autophagy-related biomarker for myotonic dystrophy type 1.

Myotonic dystrophy type I (DM1), a CTG repeat expansion hereditary disorder, is primarily characterized by myotonia. Several studies have reported that abnormal autophagy pathway has a close relationship with DM1. However, the underlying key regulatory molecules dictating autophagy disturbance still remains elusive. Previous studies mainly focused on finding targeted therapies for DM1, but the clinical heterogeneity of the DM1 is rarely addressed. Herein, to identify potential regulator genes related to autophagy and cross-correlation among clinical symptoms, we performed weighted gene co-expression network analysis (WGCNA) to construct the co-expression network and screened out 7 core autophagy-related genes (DAPK1, KLHL4, ERBB3, SESN3, ATF4, MEG3, and COL1A1) by overlapping within differentially expressed genes (DEG), cytoHubba, gene significance (GS) and module membership (MM) score. Meanwhile, we here analyzed autophagy-related molecular subtypes of DM1 in relation to the clinical phenotype. Our results show that three genes (DAPK1, SESN3, and MEG3) contribute to distinguish these two molecular subtypes of DM1. We then develop an analysis of RNA-seq data from six human skin fibroblasts (3 DM1, 3 healthy donors). Intriguingly, of the 7 hallmark genes obtained, DAPK1 is the only confirmed gene, and finally identified in vitro by RT-PCR. Furthermore, we assessed the DAPK1 accuracy diagnosis of DM1 by plotting a receiver operating characteristic curve (ROC) (AUC = 0.965). In this study, we first validated autophagy status of DM1 individuals exhibits a clearly heterogeneity. Our study identified and validated DAPK1 serve as a novel autophagy-related biomarker that correlate with the progression of DM1.

Amentoflavone inhibits colorectal cancer epithelial-mesenchymal transition via the miR-16-5p/HMGA2/ß-catenin pathway.

Background: Amentoflavone is a type of bioflavonoid that exists in many Chinese medicines and has anti-inflammatory, antioxidant, antiviral, and anticancer effects. However, the effect of amentoflavone on epithelial to mesenchymal transition (EMT) in human colorectal cancer (CRC) has not been studied. In this study, we aim to explore the effect of amentoflavone on EMT in CRC. Methods: The effects of long noncoding RNA (lncRNA) miR-16-5p on proliferation, migration, and invasion were determined by in vitro and in vivo experiments. A luciferase reporter assay was carried out to reveal the interaction between miR-16-5p and targeted genes. Reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate the expression of miR-16-5p. A western blot assay was used to detect the expression of targeted genes in CRC cells. Results: The results showed that amentoflavone significantly inhibited CRC migration, invasion, and EMT by increasing miR-16-5p expression. Mechanistically, amentoflavone induced inactivation of the Wnt/ß-catenin pathway via miR-16-5p, directly targeting 3'-UTR of HMGA2 to suppress HMGA2 expression in CRC. Clinically, combined miR-16-5p and HMGA2 levels may serve as a predictor for poor prognosis in patients with CRC. Furthermore, an in vivo PDX model suggested that amentoflavone exhibited antitumor effects in vivo via the miR-16-5p/HMGA2/ß-catenin pathway. Conclusions: This is the first study to show that amentoflavone inhibits CRC EMT via the miR-16/HMGA2/ß-catenin pathway. Amentoflavone may be beneficial in treating CRC patients in the clinic.