Over-the-scope clip as a rescue treatment for massive bleeding due to Dieulafoy lesion at the colorectal anastomosis: A case report.

RATIONALE: The bleeding of Dieulafoy lesion predominantly involves the proximal stomach and leads to severe gastrointestinal bleeding. However, these lesions have also been reported in the whole gastrointestinal tract. Bleeding of Dieulafoy lesions at the anastomosis was seldomly reported and was very easy to be ignored clinically. PATIENT CONCERNS: We describe a 72-year-old woman with a past history of surgery for rectal carcinoma hospitalized with chief complaint of massive rectal bleeding. No gross bleeding lesion was found during the first emergency colonoscopy. Despite multiple blood transfusions, her hemoglobin rapidly dropped to 5.8 g/dL. DIAGNOSIS: She was diagnosed with Dieulafoy lesion at the colorectal anastomosis during the second emergency colonoscopy. INTERVENTIONS: Primary hemostasis was achieved by endoscopic hemostatic clipping. However, she experienced another large volume hematochezia 3 days later, and then received another endoscopic hemostatic clipping. She was improved and discharged. However, this patient underwent hematochezia again 1 month later. Bleeding was arrested successfully after the over-the-scope clip (OTSC) was placed during the fourth emergency colonoscopy. OUTCOMES: This patient underwent 4 endoscopic examinations and treatments during 2 hospitalizations. The lesion was overlooked during the first emergency colonoscopy. The second and third endoscopes revealed Dieulafoy lesion at the colorectal anastomosis and performed endoscopic hemostatic clippings, but delayed rebleeding occurred. The bleeding was stopped after the fourth emergency colonoscopy using OTSC. There was no further rebleeding during hospitalization and after 2-year of follow-up. LESSONS: As far as we know, there is no reported case of lower gastrointestinal bleeding caused by Dieulafoy lesion at the colorectal anastomosis, OTSC is a safe and effective rescue treatment for Dieulafoy lesions.

Effects of the Chinese herbal formula San-Huang Gu-Ben Zhi-Ke treatment on stable chronic obstructive pulmonary disease: a randomized, double-blind, placebo-controlled trial.

Objective: The aim of this study was to evaluate the efficacy and safety of the Chinese herbal formula San-Huang Gu-Ben Zhi-Ke (SHGBZK) as a treatment for patients with stable chronic obstructive pulmonary disease (COPD) diagnosed with lung-spleen Qi deficiency. Method: A randomized, double-blind, placebo-controlled trial was designed. 98 adults aged between 40 and 80 years with stable COPD diagnosed with lung-spleen Qi deficiency were included. All participants received basic treatment for COPD. Patients in the experimental group took SHGBZK, while the control group took placebo. The primary outcome was the frequency of acute exacerbation. The secondary outcomes were lung function, symptom score, exercise capacity and quality of life. Results: Of 98 patients who underwent randomization, 50 patients in the SHGBZK group and 48 in the placebo group were included in the full analysis set. After 24-week therapy and 28-week follow-up, patients in treatment group had significant improvements in symptom, exercise capacity and quality of life. After Subgroup analysis, the frequency of acute exacerbation in patients with a COPD Assessment Test (CAT) score of at least 10 or a modified Medical Research Council (mMRC) score of at least 2 was significantly lower in the SHGBZK group than in the placebo group. Lung function in patients with frequent exacerbation was significantly higher in the SHGBZK group than in the placebo group. The incidence of adverse events was generally similar in the two groups. Conclusion: SHGBZK had beneficial effects on symptom, exercise capacity and quality of life in stable COPD patients. SHGBZK also had the potential to reduce the frequency of exacerbation and improve lung function in specific groups of COPD patients. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=26933, identifier ChiCTR1800016349.

Characterization of copper binding to different molecular weight fractions of dissolved organic matter in surface water.

Dissolved organic matter (DOM) is a kind of substance with complex compositions and wide molecular weight distribution, which can strongly combine with various pollutants. Therefore, the binding characteristics of DOM and heavy metal pollutants can be studied specifically according to the binding characteristics of DOM and pollutants. In this study, DOM in surface water bodies was divided into three levels (MW < 1 kDa, 1 kDa < MW < 5 kDa, MW > 5 kDa) according to different molecular weights (MW). The binding properties were investigated by fluorescence spectrum analysis and complex model. Four components (C1-C4) were identified by PARAFAC. Among them, the contribution rate of protein-like components C1, C2 and C4 to the total fluorescence intensity reached more than 78%, and the log Ka values of low molecular weight components were the highest, which were 3.28, 3.14 and 3.47, respectively, indicating higher binding ability with Cu2+.With the decrease of molecular weight, the log Kb value increases, indicating that the complexation is more stable. The humic component C3 in high molecular weight has stronger binding stability with Cu2+, but the number of binding sites for C3 is 0.36, while that for C2 is 1.51, indicating that its binding sites and binding ability are relatively low. The results showed that the DOM ligand of Cu2+ in surface water showed a certain molecular weight dependence. In addition, different MW DOM lead to different pollution forms. Different properties of DOM ligand combined with Cu2+ were studied in order to control the migration, transformation, bioavailability, morphology and stability of heavy metal pollutants, and to provide theoretical support for the practical application management of surface water pollution control.

The enhance mechanism of DOM on tetracyclines degradation by electrochemical technology: A improvement of treatment processes.

Tetracyclines (TC) is a typical broad-spectrum antimicrobial agent, and excessive use of TC can lead to a large accumulation of residual tetracycline in water. DOM is organic substances that can pass through the 0.45 µm filter. While dissolved organic matter (DOM) is one of the most significant substances in water, which has an important effect on water treatment. In this study, ultraviolet and visible spectrophotometry (UV-Vis) is applied to explore DOM to the effect of the electrochemical degradation. Three-dimension excitation emission matrix fluorescence spectroscopy (3D-EEM) is used to identify the component variation of DOM after the electrochemical oxidation (EO). Liquid chromatograph mass spectrometer (LC-MS) is used to confirm the degradation pathway of TC whether spontaneous or electrochemical oxidation. High performance liquid chromatography (HPLC) suggests the ROS production by DOM in the electrochemical oxidation under different conditions. Results show that DOM can promote the degradation of TC in the electrochemical oxidation. Tailwater DOM containssubstances can produce persistent free radicals, which can promote the degradation under light and dark conditions, natural source DOM can produce more free radicals under light. Therefore, TC wastewater should be added tailwater to promote the degradation of TC before the further water treatment. Otherwise, TC can be degraded to differentpathways (light, electricity, and degrade spontaneously). This study provides a significant idea for practical water treatment of tetracyclines, and promotes the practical application of electrochemical technology.

Spatiotemporal effects of meteorological conditions on global influenza peaks.

BACKGROUND: Numerous studies have suggested that meteorological conditions such as temperature and absolute humidity are highly indicative of influenza outbreaks. However, the explanatory power of meteorological factors on the seasonal influenza peaks varied widely between countries at different latitudes. OBJECTIVES: We aimed to explore the modification effects of meteorological factors on the seasonal influenza peaks in multi-countries. METHODS: Data on influenza positive rate (IPR) were collected across 57 countries and data on meteorological factors were collected from ECMWF Reanalysis v5 (ERA5). We used linear regression and generalized additive models to investigate the spatiotemporal associations between meteorological conditions and influenza peaks in cold and warm seasons. RESULTS: Influenza peaks were significantly correlated with months with both lower and higher temperatures. In temperate countries, the average intensity of cold season peaks was stronger than that of warm season peaks. However, the average intensity of warm season peaks was stronfger than of cold season peaks in tropical countries. Temperature and specific humidity had synergistic effects on influenza peaks at different latitudes, stronger in temperate countries (cold season: R2=0.90; warm season: R2=0.84) and weaker in tropical countries (cold season: R2=0.64; warm season: R2=0.03). Furthermore, the effects could be divided into cold-dry and warm-humid modes. The temperature transition threshold between the two modes was 16.5-19.5 °C. During the transition from cold-dry mode to warm-humid mode, the average 2 m specific humidity increased by 2.15 times, illustrating that transporting a large amount of water vapor may compensate for the negative effect of rising temperatures on the spread of the influenza virus. CONCLUSION: Differences in the global influenza peaks were related to the synergistic influence of temperature and specific humidity. The global influenza peaks could be divided into cold-dry and warm-humid modes, and specific thresholds of meteorological conditions were needed for the transition of the two modes.

Better response to Tanreqing injection in frequent acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients-Real-world evidence from a nationwide registry (ACURE) study.

Objective: Our aim was to systematically investigate the efficacy of Tanreqing (TRQ) injection on in-hospital outcomes among inpatients with frequent or infrequent AECOPD. Methods: In this ongoing, nationwide multicenter registry designed to investigate clinical characteristics, management, and prognoses of Chinese patients admitted for AECOPD in real-world settings, we collected characteristics, comorbidities, in-hospital prognoses, and information on the COPD assessment test (CAT) questionnaire, PEACE questionnaire, and modified British Medical Research Council (mMRC) questionnaire from each enrolled patient. Frequent AECOPD was determined as being admitted to the hospital ≥1 time or visiting the emergency room (ER) ≥ 2 times due to AECOPD within a year. A propensity match method and univariable and multivariable regression models were performed to analyze the efficacy of TRQ on clinical outcomes for inpatients with frequent AECOPD. Results: A total of 4135 inpatients were involved in the analysis, including 868 administered with TRQ and 3267 not administered with TRQ. After propensity score match, among those administered with TRQ, 493 had frequent AECOPD and 358 had infrequent AECOPD. A significant reduction of CAT score at discharge (TRQ median 12, IQR 8.0-16.0; non-TRQ median 13, IQR 9.0-18.0, p = 0.0297), a lower rate of ICU admission (TRQ 0.8% vs. non-TRQ 2.6%, p = 0.0191), and a shorter length of stay (LOS) (TRQ median 11, IQR 9.0-14.0; non-TRQ median 11, IQR 8.0-14.0, p = 0.004) were observed in the TRQ group, compared with the non-TRQ group among frequent AECOPD patients. In the subgroup analysis, for those with a PEACE score >7 on admission, TRQ contributed to a significantly lower CAT score at discharge (p = 0.0084) and a numerically lower ICU admission rate with a marginal statistical significance. Among those with phlegm-heat symptom complex on admission ≥2, a lower CAT score at discharge and a lower ICU admission were also observed in the TRQ group. Conclusion: TRQ injection had better efficacy in patients with frequent AECOPD in reducing ICU admission and alleviating respiratory symptoms, especially for those with higher severity on admission or more phlegm-heat symptoms.

Plant-Derived Biomaterials and Their Potential in Cardiac Tissue Repair.

Cardiovascular disease remains the leading cause of mortality worldwide. The inability of cardiac tissue to regenerate after an infarction results in scar tissue formation, leading to cardiac dysfunction. Therefore, cardiac repair has always been a popular research topic. Recent advances in tissue engineering and regenerative medicine offer promising solutions combining stem cells and biomaterials to construct tissue substitutes that could have functions similar to healthy cardiac tissue. Among these biomaterials, plant-derived biomaterials show great promise in supporting cell growth due to their inherent biocompatibility, biodegradability, and mechanical stability. More importantly, plant-derived materials have reduced immunogenic properties compared to popular animal-derived materials (e.g., collagen and gelatin). In addition, they also offer improved wettability compared to synthetic materials. To date, limited literature is available to systemically summarize the progression of plant-derived biomaterials in cardiac tissue repair. Herein, this paper highlights the most common plant-derived biomaterials from both land and marine plants. The beneficial properties of these materials for tissue repair are further discussed. More importantly, the applications of plant-derived biomaterials in cardiac tissue engineering, including tissue-engineered scaffolds, bioink in 3D biofabrication, delivery vehicles, and bioactive molecules, are also summarized using the latest preclinical and clinical examples.

Idebenone attenuates ferroptosis by inhibiting excessive autophagy via the ROS-AMPK-mTOR pathway to preserve cardiac function after myocardial infarction.

Cardiovascular diseases (CVDs) are the leading causes of mortality worldwide. As a type of CVDs, myocardial infarction (MI) induces ischemia hypoxia, which leads to excessive reactive oxygen species (ROS), resulting in multiple cell deaths and contributing to the subsequent development of heart failure or premature death. Recent evidence indicates that ROS-induced lipid peroxidation promotes autophagy and ferroptosis, leading to the loss of healthy myocardium and resulting in the dysfunction of cardiac tissue. Theoretically, cardiac function would be preserved after MI by inhibiting autophagy and ferroptosis. As an analog of coenzyme Q10 (CoQ10) and a clinically approved drug, idebenone would be used to inhibit ferroptosis and preserve cardiac function due to its capacity to improve mitochondrial physiology with antioxidant and anti-inflammatory properties. Here, we confirmed that the addition of idebenone inhibited H2O2-induced and RSL3-induced ferroptosis. Furthermore, the ROS-AMPK-mTOR pathway axis was identified as the signaling pathway that idebenone stimulated to prevent excessive autophagy and consequent ferroptosis. In the MI animal model, idebenone demonstrated a cardioprotective role by regulating ROS-dependent autophagy and inhibiting ferroptosis, which paves the way for the future clinical translation of idebenone in MI management.

Soil ammonium (NH4+) toxicity thresholds for restoration grass species.

Ionic rare earth mining has resulted in large amounts of bare soils, and revegetation success plays an important role in mine site rehabilitation and environmental management. However, the mining soils still maintain high NH4+ concentrations that inhibit plant growth and NH4+ toxicity thresholds for restoration plants have not been established. Here we investigated the NH4+ toxicological effects and provided toxicity thresholds for grasses (Lolium perenne L. and Medicago sativa L.) commonly used in restoration. The results show that high NH4+ concentration not only reduces the plant biomass and soluble sugars in leaves but also increases the H2O2 and MDA content, and SOD, POD, and GPX activities in roots. The SOD activities and root biomass can be adopted as the most NH4+ sensitive biomarkers. Six ecotoxicological endpoints (root biomass, soluble sugars, proline, H2O2, MDA, and GSH) of ryegrass, eight ecotoxicological endpoints (root biomass, soluble sugars, proline, MDA, SOD, POD, GPX, and GSH) of alfalfa were selected to determine the threshold concentrations. The toxicity thresholds of NH4+ concentrations were proposed as 171.9 (EC5), 207.8 (EC10), 286.6 (EC25), 382.3 (EC50) mg kg-1 for ryegrass and 171.9 (EC5), 193.2 (EC10), 234.7 (EC25), 289.6 (EC50) mg kg-1 for alfalfa. The toxicity thresholds and the relation between plant physiological indicators and NH4+ concentrations can be used to assess the suitability of the investigated plants for ecological restoration strategies.

[Advancements in virtual screening techniques for study of enzyme inhibitor compounds].

Enzymes are closely associated with the onset and progression of numerous diseases, making enzymes a primary target in innovative drug development. However, the challenge remains in identifying compounds that exhibit potent inhibitory effects on the target enzymes. With the continuous expansion of the total number of natural products and increasing difficulty in isolating and enriching new compounds, traditional high-throughput screening methods are finding it increasingly challenging to meet the demands of new drug development. Virtual screening, characterized by its high efficiency and low cost, has gradually become an indispensable technology in drug development. It represents a prominent example of the integration of artificial intelligence with biopharmaceuticals and is an inevitable trend in the rapid development of innovative drug screening in the future. Therefore, this article primarily focused on systematically reviewing the recent applications of virtual screening technology in the development of enzyme inhibitors and explored the prospects and advantages of using this technology in developing new drugs, aiming to provide essential theoretical insights and references for the application of related technologies in the field of new drug development.

The Efficacy and Safety of Xinjia Xuanbai Chengqi Granules in Acute Exacerbation of COPD: A Multicentre, Randomised, Double-Blind, Controlled Trial.

Purpose: The study aimed to explore the efficacy and safety of Xinjia Xuanbai Chengqi granules (XJXBCQ) combined with conventional medicine in the treatment of acute exacerbation of chronic pulmonary disease (AECOPD). Patients and Methods. This multicentre, double-blind, parallel, placebo-controlled, randomised clinical trial conducted in China from January 2019 to February 2021 recruited 330 participants who were allocated into three groups. All participants underwent conventional basic treatment with oxygen therapy, antibiotics, and a bronchodilator. Besides, group A received XJXBCQ granules and budesonide suspension for inhalation; group B received XJXBCQ granules and half dosage of budesonide suspension; and group C received budesonide suspension and a placebo. All therapies lasted for 5 days, and participants were followed up for 30 days after discharge. The primary outcomes were efficacy, traditional Chinese medicine (TCM) syndrome score, and clinical symptom score. Secondary outcomes included the blood gas analysis, serum inflammatory markers, adverse events, mortality, theoretical discharge time, actual hospitalisation time, proportion of patients requiring invasive mechanical ventilation, proportion of patients transferred to an intensive care unit (ICU), and readmission rate within 30 days after discharge. Results: XJXBCQ adjunct with conventional treatment could significantly improve the total efficacy (P < 0.05). Meanwhile, group A showed significantly better results than group C in the TCM syndrome score, phlegm score, and Wexner constipation score (P < 0.05). For modified British medical research council (mMRC), on day 3 (-0.17, 95% confidence interval [CI]: -0.33--0.01) and day 4 (-0.20, 95% CI: -0.39--0.02), group A performed statistically better than group C. No significant differences in other secondary outcomes were detected. Conclusion: XJXBCQ is beneficial and safe for AECOPD treatment and could be considered an adjunctive therapy for promoting the relief of clinical symptoms. This trial is registered with ChiCTR1800016915.

Advanced oxidation processes and selection of industrial water source: A new sight from natural organic matter.

Natural organic matter (NOM) refers to the dissolved organic matter in natural water that can pass through 0.45 µm filter membrane. As a pivotal role in the surface water body, it has a significant effect on the efficiency of AOPs. In this study, Excitation emission matrix - parallel factor (EEM-PARAFAC) analysis is used to elucidate the changes of NOM fluorescence peaks after electrochemical oxidation process, two-dimensional correlation spectroscopy (2D-FTIR-COS) and Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) are utilized to clarify the molecular characteristics of NOM in surface water and the effects of electrochemical oxidation on NOM molecules. The results indicate that parts of NOM molecules are mineralized into simple compounds and precursors of refractory organic matters produced by some NOM molecules after AOPs. It is concluded that the precursors of these refractory organic matters may belong to terrestrial humus (C2). Therefore, for the purpose of avoiding more refractory organic pollutants produced by NOM which can reduce the performance of AOPs in the water treatment process, factories should choose water sources with less humus as industrial water supply, or degrade humus by physical or chemical methods before industrial water supply.

Surgical treatment of type A acute aortic dissection with cerebral malperfusion: a systematic review.

OBJECTIVES: Type A acute aortic dissection (TAAAD) complicated with cerebral malperfusion (CM) is a life-threatening condition associated with high mortality, poor outcomes, and the optimal surgical management remains controversial. The aim of this review was to report the current results of surgical interventions of these patients. METHODS: A systematic review was performed using PubMed and MEDLINE search for cases underwent surgical repair for TAAAD with CM. Demographics, neurological symptom, the time from onset of symptoms to operation, operation data, mortality, neurological outcome, and follow-up were reviewed. RESULTS: A total of 363 patients with mean age of 65.7 ± 13 years underwent surgical repair for TAAAD with CM were identified in 12 retrospective studies. In-hospital mortality was 20.1%. Mean duration of follow-up was 40.1 ± 37.6 months. The involved supra-aortic branch vessels were RCCA (n = 99), LCCA (n = 25), B-CCA (n = 52), CCA (n = 131), IA (n = 19), and LSA (n = 8). Time from onset of neurological symptoms to surgery was 13.3 h. Antegrade and/or retrograde cerebral perfusion were applied. Postoperatively, improved, unchanged and worsened neurological status was occurred in 54.3%, 27.1%, and 8.5%, respectively in 199 patients. CONCLUSION: The outcomes of surgical treatment of TAAAD complicated with CM indicate acceptable early mortality and morbidity. It is reasonable to perform lifesaving surgery on these patients. Early central surgical repair and reperfusion of brain may improve the outcomes.

Retrosplenial Cortex Effects Contextual Fear Formation Relying on Dysgranular Constituent in Rats.

Animal contextual fear conditioning (CFC) models are the most-studied forms used to explore the neural substances of posttraumatic stress disorder (PTSD). In addition to the well-recognized hippocampal-amygdalar system, the retrosplenial cortex (RSC) is getting more and more attention due to substantial involvement in CFC, but with a poor understanding of the specific roles of its two major constituents-dysgranular (RSCd) and granular (RSCg). The current study sought to identify their roles and underlying brain network mechanisms during the encoding processing of the rat CFC model. Rats with pharmacologically inactivated RSCd, RSCg, and corresponding controls underwent contextual fear conditioning. [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scanning was performed for each animal. The 5-h and 24-h retrieval were followed to test the formation of contextual memory. Graph theoretic tools were used to identify the brain metabolic network involved in encoding phase, and changes of nodal (brain region) properties linked, respectively, to disturbed RSCd and RSCg were analyzed. Impaired retrieval occurred in disturbed RSCd animals, not in RSCg ones. The RSC, hippocampus (Hip), amygdala (Amy), piriform cortex (Pir), and visual cortex (VC) are hub nodes of the brain-wide network for contextual fear memory encoding in rats. Nodal degree and efficiency of hippocampus and its connectivity with amygdala, Pir, and VC were decreased in rats with disturbed RSCd, while not in those with suppressed RSCg. The RSC plays its role in contextual fear memory encoding mainly relying on its RSCd part, whose condition would influence the activity of the hippocampal-amygdalar system.

Growth factors: avenues for the treatment of myocardial infarction and potential delivery strategies.

Acute myocardial infarction (AMI) is one of the leading causes of death worldwide. Despite recent advances in clinical management, reoccurence of heart failure after AMI remains high, in part because of the limited capacity of cardiac tissue to repair after AMI-induced cell death. Growth factor-based therapy has emerged as an alternative AMI treatment strategy. Understanding the underlying mechanisms of growth factor cardioprotective and regenerative actions is important. This review focuses on the function of different growth factors at each stage of the cardiac repair process. Recent evidence for growth factor therapy in preclinical and clinical trials is included. Finally, different delivery strategies are reviewed with a view to providing workable strategies for clinical translation.

Acute myocardial infarction is a serious, life-threatening disease. Current treatments for acute myocardial infarction are unsatisfactory, and new treatments are required. Growth factors are promising treatments for myocardial infarction. It is intriguing to understand how growth factors provide cardioprotective benefits. This article describes the various growth factors used to treat myocardial infarction and how they are delivered to the infarcted heart.

Suhuang Antitussive Capsule Ameliorates Corticosteroid Insensitivity in Cough Variant Asthma Guinea Pigs by Inhibiting p38 MAPK Signal Pathway.

Methods: The CVA guinea pig model was successfully established by use of ovalbumin (OVA) sensitization and cigarette smoke (CS) exposure. The guinea pigs were divided into 6 groups: a control group, an OVA model group, an OVA + CS model group, a Suhuang treatment group, a BUD treatment group, and a combination (Suhuang and BUD) treatment group. The effects of the treatment were determined by measuring lung function (RI/Cydn) and cough symptoms (coughs number/cough latency) as outcome criteria. The levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were determined by ELISA. Lung tissues were stained by hematoxylin and eosin (H&E). The expressions of GR/total p38 MAPK/p-p38 MAPK were detected by Western blot. The MKP-1 mRNA levels were detected by RT-PCR. Results: Combination treatment significantly decreased RI/coughs numbers and increased Cydn/cough latency. Significantly, the results indicated that combination treatment decreased injury to pulmonary tissues. Results also revealed that levels of inflammatory cytokines were reduced in all treatment groups but most markedly in the combination treatment group. Moreover, Suhuang treatment significantly ameliorated corticosteroid insensitivity by improving the expression of glucocorticoid receptors (GR). The expressions of total p38 MAPK and p-p38 MAPK in lung tissue were significantly inhibited in the Suhuang and combination treatment groups. The MKP-1 mRNA levels in Suhuang and combination treatment groups were also increased significantly. Conclusion: Suhuang was effective for reversing corticosteroid insensitivity by regulating the p38 MAPK signal pathway, and combining BUD and Suhuang treatment showed synergistic interactions in CVA guinea pigs. Our findings showed that this combination therapy might be a promising therapeutic agent for CVA and also clarified its underlying mechanism of action, providing a theoretical basis for clinical combination treatment with Suhuang and BUD in CVA patients.

Bone metastasis of esophageal carcinoma diagnosed as a first primary tumor: a population-based study.

Background: This study aimed to explore predictors of bone metastasis (BM) of esophageal carcinoma (EC) and factors affecting the prognosis of EC with BM (ECBM). Methods: We retrospectively studied the data of EC patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. Logistic regression analysis was used to analyze the risk factors of BM. Cox regression and Fine and Gray's competing risk regression were performed to identify prognostic factors associated with all-cause and cancer-specific death, respectively. The Kaplan-Meier method was used to assess survival. Results: After exclusion, 8,916 patients were eligible, of whom 462 (5.2%) had ECBM. Independent risk factors of BM were age <65 years, male sex, stage T1, advanced N stage, and non-bone organ metastases. For EC, the median survival time (MST) was 17 months, and the 3- and 5-year survival rates were 31.6% and 23.3%, respectively; meanwhile, for BM, the MST was 5 months, and the 3- and 5-year survival rates were 2% and 1%, respectively. Adenocarcinoma, stage T2, the absence of non-bone organ metastases, and combined radiotherapy and chemotherapy were associated with a reduced risk of all-cause death in ECBM patients. Stage T2, the absence of non-bone organ metastases, and combined radiotherapy and chemotherapy were associated with a decreased risk of cancer-specific death in ECBM patients. Conclusions: Although rare, BM severely impairs the prognosis of EC. BM predictors and factors influencing the prognosis of ECBM may help distinguish high-risk patients with BM and assess survival in ECBM patients.

Fluoride regulates chondrocyte proliferation and autophagy via PI3K/AKT/mTOR signaling pathway.

Fluorine is an essential trace element for human health. However, excessive fluoride intake causes skeletal fluorosis which affects cartilage development. Fluoride inhibited chondrocyte proliferation which is the initial and critical step of endochondral ossification, but the underlying mechanism has not been clearly illustrated. Mammalian target of rapamycin (mTOR) is an important protein kinase which modulates various cellular processes and is believed to be a central regulator of chondrocyte proliferation and autophagy. In this study, we explored the effect of fluoride on the proliferation and autophagy of chondrocytes and the regulatory role of mTOR signaling pathway. Our results suggested that NaF inhibited the protein expressions of proliferating cell nuclear antigen (PCNA) and pS6 in cultured fetal rat tibias. Furthermore, NaF significantly downregulated the expressions of mTOR signaling pathway-related genes, including PI3K, AKT, mTOR, 4EBP1 and S6K1 in mouse ATDC5 chondrogenic cell line. We also found that NaF increased autophagy in ATDC5 cells. The mRNA and protein levels of autophagy-related genes LC3, Beclin1 and p62 were significantly changed after NaF treatment. Further studies demonstrated that MHY1485, a small-molecular mTOR activator, totally reversed fluoride-induced promotion of autophagy. MHY1485 also recovered the downregulation of proliferative chondrocytes markers Sox9 and Type Ⅱ Collagen (Col2a1) induced by fluoride in ATDC5 cells. Taken together, our result demonstrate that fluoride suppressed proliferation and facilitated autophagy via PI3K/AKT/mTOR signaling pathway in chondrogenesis.

Dysregulation of miR-342-3p in plasma exosomes derived from convalescent AMI patients and its consequences on cardiac repair.

Plasma exosomes derived from healthy people have been shown to be beneficial in terms of protecting against ischemia-reperfusion injury or acute myocardial infarction (AMI). However, a pathological condition may severely affect the constitution and biological activity of exosomes. In our study, we isolated plasma exosomes from healthy volunteers and convalescent AMI patients (3-7 d after onset). Compared to exosomes from healthy controls (Nor-Exo), exosomes from convalescent AMI patients (AMI-Exo) exhibited an impaired ability to repair damaged cardiomyocytes both in vitro and in vivo. miRNA sequencing and PCR analysis indicated that miR-342-3p was significantly downregulated in AMI-Exo. Moreover, miR-342-3p alleviated H2O2-induced injury and reduced apoptosis and autophagy in H9c2 cardiomyocytes, while in vivo restoration of miR-342-3p expression enhanced the reparative function of AMI-Exo. Further mechanistic studies revealed that the SOX6 and TFEB genes were two direct and functional targets of miR-342-3p. Taken together, during the early convalescent phase after AMI, dysregulated miR-342-3p in plasma exosomes might be responsible for their impaired cardioprotective potential. miR-342-3p contributed to exosome-mediated heart repair by inhibiting cardiomyocyte apoptosis and autophagy through targeting SOX6 and TFEB, respectively. Our work provided novel insights on the role of plasma exosomes in the natural process of cardiac repair after AMI and suggestions for therapy development.