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Objective Coronavirus disease 2019 (COVID-19) is often accompanied by gastrointestinal symptoms, which are related to gut microbiota dysbiosis (GMD). Whether washed microbiota transplantation (WMT) is an effective treatment for COVID-19 patients suspected of having GMD by restoring the gut microbiota is unknown. This study is designed to explore the efficacy and safety of WMT in COVID-19 patients suspected of having GMD. Methods This is a randomized, multicenter, single-blind prospective study. COVID-19 patients suspected of having GMD will be randomly divided to receive routine treatment only or to receive routine treatment and WMT. The frequency of WMT will be once a day for three consecutive days. Laboratory and imaging examinations will be performed at admission, 1 and 2 weeks after treatment, and on the day of discharge. Then a telephone follow-up will be conducted at 1st week, 2nd week, and 6th month after discharge. The clinical efficacy and safety of WMT in COVD-19 patients suspected of having GMD and the effects of WMT on the organ function, homeostasis, inflammatory response, intestinal mucosal barrier function, and immunity of the patients will be evaluated. Results By following the proposed protocol, WMT is expected to be efficacious and safe for the treatment of COVID-19 patients suspected of having GMD, and the therapeutic effect is expected to be associated with improvement of the intestinal mucosal barrier function, inflammatory response, and immunity. Conclusion The findings from this study may offer a new approach for the prevention and treatment of COVID-19 patients suspected of having GMD. Electronic supplementary material The online version of this article (10.1007/s11596-021-2475-2) contains supplementary material, which is available to authorized users.

Purpose To investigate the dosimetric impact of deep learning-based auto-segmentation of organs at risk (OARs) on nasopharyngeal and rectal cancer. Methods and materials Twenty patients, including ten nasopharyngeal carcinoma (NPC) patients and ten rectal cancer patients, who received radiotherapy in our department were enrolled in this study. Two deep learning-based auto-segmentation systems, including an in-house developed system (FD) and a commercial product (UIH), were used to generate two auto-segmented OARs sets (OAR_FD and OAR_UIH). Treatment plans based on auto-segmented OARs and following our clinical requirements were generated for each patient on each OARs sets (Plan_FD and Plan_UIH). Geometric metrics (Hausdorff distance (HD), mean distance to agreement (MDA), the Dice similarity coefficient (DICE) and the Jaccard index) were calculated for geometric evaluation. The dosimetric impact was evaluated by comparing Plan_FD and Plan_UIH to original clinically approved plans (Plan_Manual) with dose-volume metrics and 3D gamma analysis. Spearman’s correlation analysis was performed to investigate the correlation between dosimetric difference and geometric metrics. Results FD and UIH could provide similar geometric performance in parotids, temporal lobes, lens, and eyes (DICE, p > 0.05). OAR_FD had better geometric performance in the optic nerves, oral cavity, larynx, and femoral heads (DICE, p p p = 0.05). Only one significant correlation was found between the mean dose of the femoral head and its HD index (R = 0.4, p = 0.01), there is no OARs showed strong correlation between its dosimetric difference and all of four geometric metrics. Conclusions Deep learning-based OARs auto-segmentation for NPC and rectal cancer has a nonsignificant impact on most PTV and OARs dose-volume metrics. Correlations between the auto-segmentation geometric metric and dosimetric difference were not observed for most OARs.

Objectives This study aimed to investigate whether plasma levels of adenosine, adenosine deaminase (ADA), and certain cytokines change in patients with chronic insomnia disorder (CID), and if so, whether these alterations are associated with poor sleep quality and cognitive dysfunction. Methods Fifty-five CID patients were selected for the study, along with fifty-five healthy controls (HC) matched to the patients according to their basic data. All subjects completed sleep, emotion, and cognition assessments, with some CID patients also completing an overnight polysomnography. The plasma level of adenosine was measured using liquid chromatography–tandem mass spectrometry, while ADA level was quantified using a quantitative sandwich enzyme-linked immunosorbent assay. Levels of cytokines, including IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, TNF-α, and IFN-γ, were measured using Luminex liquid chip technology. Results CID patients had a lower adenosine level, and higher levels of ADA and some of the cytokines (IL-1β, IL-2, IL-6, IL-10 and TNF-α) compared with controls. In the CID group, plasma concentrations of adenosine were negatively correlated with Pittsburgh Sleep Quality Index scores, while concentrations of IL-1β, IL-6 and TNF-α were positively correlated with these scores. Concentrations of IL-1β and TNF-α were negatively correlated with scores on the Chinese-Beijing Version of the Montreal Cognitive Assessment. Moreover, levels of IL-1β, TNF-α, IL-6, and IL-2 were positively correlated with memory test errors by CID patients after controlling for confounding factors. Conclusions The reduced adenosine and elevated cytokine levels of CID patients were associated with the severity of insomnia and/or cognitive dysfunction.

Displaced aggressive behaviour is associated with many negative outcomes. Although certain personality traits predict displaced aggressive behaviour, the uniquely longitudinal effect of indigenous interpersonal traits on displaced aggressive behaviour is ignored. To address this gap, we explored the longitudinal relationship among an indigenously interpersonal trait of China (interpersonal openness), hostile attribution bias, and self-reported displaced aggressive behaviour. Additionally, we tested whether hostile attribution bias mediated the relationship between interpersonal openness and self-reported displaced aggressive behaviour. The Interpersonal Self-Support Scale for Undergraduate Students, Word Sentence Association Paradigm for Hostility, Displaced Aggression Questionnaire, and the NEO Personality Inventory-3 were administered to 942 undergraduates on two occasions, 6 months apart. A cross-lagged model showed that, after controlling for the Big Five personality traits, interpersonal openness predicted subsequent hostile attribution bias, and hostile attribution bias predicted self-reported displaced aggressive behaviour 6 months later. Hostile attribution bias at time 2 mediated the relationship between interpersonal openness at time 1 and self-reported displaced aggressive behaviour at time 2. These results were consistent with the interpersonal self-support theory's appraisals of interpersonal openness, and they extended the social information processing and general aggression models to explain displaced aggressive behaviour.

Background The pathogenesis of gastroesophageal reflux disease (GERD) is closely associated with the intestinal bacteria composition and their metabolites. Aim To investigate whether washed microbiota transplantation (WMT) improves symptoms of nonerosive reflux disease (NERD) with proton pump inhibitor (PPI) dependency. Methods Patients with recurrent NERD and PPI dependency at the First Affiliated Hospital of Guangdong Pharmaceutical University from 2017 to 2018 were included and divided into a WMT or PPI group treated with PPI with/without WMT. The endpoint was NERD symptom frequency evaluated 1 mo after WMT using reflux disease questionnaire (RDQ) and GERD questionnaire (GERDQ) scores, remission time, PPI dose, and the examination of intestinal mucosal barrier function. Results In the WMT (n = 15) and PPI (n = 12) groups, the total remission rate at 1 mo after treatment was 93.3% vs 41.7%. Compared with the PPI group, the WMT group showed better results in GERDQ (P = 0.004) and RDQ (P = 0.003) and in remission months (8 vs 2, P = 0.002). The PPI dose was reduced to some extent for 80% of patients in the WMT group and 33.3% in the PPI group. In 24 patients, intestinal mucosal barrier function was examined before treatment, and changes in the degree of damage were observed in 13 of these patients after treatment. Only one of the 15 patients had minor side effects, including a mushy stool two or three times a day, which resolved on their own after 1 wk. Conclusion This study is the first to demonstrate that WMT may be safe and effective for relieving NERD symptoms and reducing PPI dependency and recurrence.

Improved methods are needed to predict outcomes in biliary tract cancers (BTCs). We aimed to build an immune-related signature and establish holistic models using machine learning. Samples were from 305 BTC patients treated with curative-intent resection, divided into derivation and validation cohorts in a two-to-one ratio. Spatial resolution of T cell infiltration and PD-1/PD-L1 expression was assessed by immunohistochemistry. An immune signature was constructed using classification and regression tree. Machine learning was applied to develop prediction models for disease-specific survival (DSS) and recurrence-free survival (RFS). The immune signature composed of CD3+, CD8+, and PD-1+ cell densities and PD-L1 expression within tumor epithelium significantly stratified patients into three clusters, with median DSS varying from 11.7 to 80.8 months and median RFS varying from 6.2 to 62.0 months. Gradient boosting machines (GBM) outperformed rival machine-learning algorithms and selected the same 11 covariates for DSS and RFS prediction: immune signature, tumor site, age, bilirubin, albumin, carcinoembryonic antigen, cancer antigen 19-9, tumor size, tumor differentiation, resection margin, and nodal metastasis. The clinical-immune GBM models accurately predicted DSS and RFS, with respective concordance index of 0.776–0.816 and 0.741–0.781. GBM models showed significantly improved performance compared with tumor-node-metastasis staging system. The immune signature promises to stratify prognosis and allocate treatment in resected BTC. The clinical-immune GBM models accurately predict recurrence and death from BTC following surgery.

Aim. The fecal microbiota transplantation by washed preparation was recently coined as washed microbiota transplantation (WMT). This pilot study is aimed at exploring the feasibility and efficacy of WMT on Helicobacter pylori eradication. Methods. Consecutive patients who had been treated with WMT for various indications and who were positive for H. pylori infection before WMT treatment but had never received eradication therapy for H. pylori infection were invited to take a follow-up 13C-urea breath test. The associations of demographic, clinical factors, and laboratory indicators for gastric function and intestinal barrier function with the therapeutic effect were determined. Results. A total of 32 eligible patients were included, and the overall H. pylori eradication rate was 40.6% (13/32). Patients with H. pylori eradication had a higher pepsinogen ratio (PGR) than those without ( 13.00 ± 6.97 vs. 8.31 ± 3.733 ; P = 0.02 ). Female patients had a higher, albeit not statistically significant, eradication rate than male patients (53.85% vs. 31.58%; P = 0.208 ). Compared with lower gastrointestinal tract delivery route, middle gastrointestinal tract delivery route seems to be a more suitable way for the treatment of H. pylori infection (58.33% vs 16.67%; P = 0.152 ). There was no significant difference in other demographic and clinical factors between patients with and without H. pylori eradication. Conclusion. H. pylori infection is eradicated in a proportion of patients who have received WMT. An increased pre-WMT PGR appears to be associated with the therapeutic effect. Further studies are required to confirm the efficacy of WMT, especially in combination with currently recommended regimens in randomized controlled trials.

Registration between the baseline and follow-up lung computed tomography (CT) volumes plays an important role in computer-aided diagnosis and following-up care during adaptive radiotherapy. Diffeom...

Aggression is a type of negative social behavior. Agreeableness and anger-related cognition are thought to be important factors that affect aggression. The longitudinal relations among agreeableness, anger-related cognition and aggression, and the affective cognitive path underlying the relationship between agreeableness and aggression are not clear, however. In this study, 942 college students were investigated twice at an interval of six months, using the Buss-Perry Aggression Questionnaire, Anger Rumination Scale, and agreeableness subscale of the NEO Five-Factor Inventory. The results indicate that: agreeableness negatively predicts anger rumination and aggression after six months; anger rumination positively predicts aggression over time; and anger rumination mediates the longitudinal association between agreeableness and aggression. These results suggest that the prosocial personality may withstand aggression through resisting anger-related cognition. This study deepens our understanding of the relationships between personality and aggression, allowing a development of the General Aggression Model, in terms of recognizing the cognitive pathway for personality to influence aggression, and provides theoretical guidance on reducing the generation of aggression in daily life.

Hypoxic tumor microenvironment(TME) is a universal feature in solid carcinoma and is associated with unfavorable prognosis. Tumor-derived exosomes are now significantly implicating in mediating cellular communication and interactions in TME. The aim of this study was to identify exosomal miR-301a-3p involved in gastric cancer(GC) progression and metastasis. Here, we found hypoxia promote GC exosomes release and miR-301a-3p expression in an HIF-1α-dependent manner. In hypoxic TME, enriched miR-301a-3p could be transmitted between GC cells via exosomes and then contributed to inhibit HIF-1α degradation through targeting PHD3, that were capable to hydroxylate HIF-1α subunits to ubiquitinate degradation. This synergistical positive feedback loop between HIF-1α and miR-301a-3p facilitated GC proliferation, invasion, migration, and epithelial-mesenchymal transition. In clinical samples, we further discovered circulating exosomal miR-301a-3p in serum was positively related with peritoneal metastasis. Collectively, these data indicate that GC cells could generate miR-301a-3p-rich exosomes in the hypoxic TME, which then help to HIF-1α accumulation and promote GC malignant behaviors and metastasis. Exosomal miR-301a-3p/HIF-1α signaling axis may serve as a promising predictor and potential therapeutic target of GC with metastasis.

Coronavirus disease 2019 (COVID-19) is a novel and lethal infectious disease, posing a threat to global health security. The number of cases has increased rapidly, but no data concerning kidney transplant (KTx) recipients infected with COVID-19 are available. To present the epidemiological, clinical, and therapeutic characteristics of KTx recipients infected with COVID-19, we report on a case series of five patients who were confirmed as having COVID-19 through nucleic acid testing (NAT) from January 1, 2020 to February 28, 2020. The most common symptoms on admission to hospital were fever (five patients, 100%), cough (five patients, 100%), myalgia or fatigue (three patients, 60%), and sputum production (three patients, 60%); serum creatinine or urea nitrogen levels were slightly higher than those before symptom onset. Four patients received a reduced dose of maintenance immunosuppressive therapy during hospitalization. As of March 4, 2020 NAT was negative for COVID-19 in three patients twice in succession, and their computed tomography scans showed improved images. Although greater patient numbers and long-term follow-up data are needed, our series demonstrates that mild COVID-19 infection in KTx recipients can be managed using symptomatic support therapy combined with adjusted maintenance immunosuppressive therapy.

Aims Phenylketonuria (PKU), which is caused by mutations in the phenylalanine hydroxylase (PAH) gene, is one of the most common inherited diseases of amino acid metabolism. Phenylketonuria is characterized by an abnormal accumulation of phenylalanine and its metabolites in body fluids and brain tissues, subsequently leading to severe brain dysfunction. Various pathophysiological and molecular mechanisms underlying brain dysfunction in PKU have been described. However, the metabolic changes and their impacts on the function of cerebral cortices of patients with PKU remain largely unknown. Methods We measured the levels of small molecule metabolites in the cerebrocortical tissues of PKU mice and wild-type control mice using liquid chromatography-mass spectrometry (LC-MS)-based metabolome analysis. Differential metabolites were further subjected to metabolic pathway and enrichment analysis. Results Metabolome analysis revealed 35 compounds among 143 detected metabolites were significantly changed in PKU mice as compared to those in their wild-type littermates. Metabolic pathway and enrichment analysis of these differential metabolites showed that multiple metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis; valine, leucine, and isoleucine biosynthesis; alanine, aspartate, and glutamate metabolism; purine metabolism; arginine and proline metabolism and methionine metabolism, were impacted in the cerebral cortices of PKU mice. Conclusions The data revealed that multiple metabolic pathways in cerebral cortices of PKU mice were disturbed, suggesting that the disturbances of the metabolic pathways might contribute to neurological or neurodevelopmental dysfunction in PKU, which could thus provide new insights into brain pathogenic mechanisms in PKU as well as mechanistic insights for better understanding the complexity of the metabolic mechanisms of the brain dysfunction in PKU.

Background and aim This study aimed to investigate the postoperative quality of life (QOL) between laparoscopy-assisted pylorus-preserving gastrectomy (LAPPG) and laparoscopy-assisted distal gastrectomy with Billroth I anastomosis (LADGBI) in patients with middle-third early gastric cancers (EGC). Methods From January 2015 to August 2017, a total 91 patients with EGC underwent LAPPG or LADGBI procedure with complete QLQ-C30 and QLQ-STO22 in Ren Ji Hospital. Not only do surgical and oncological safety as well as clinicopathologic characteristics analyze, but also chronological changes of QOL and nutritional status were compared for the evaluation of functional advantages. Results There was no significant difference in clinicopathologic characteristics and perioperative recovery between LAPPG and LADGBI. During postoperative 2-year follow up, LAPPG showed significant advantages over LADGBI in emotional functioning, insomnia, appetite loss, reflux, and taste problem and presented larger area in global and functional scales and less area in symptom scales, which means that LAPPG tended to present better improvement and less symptoms than LADGBI for QOL 2 years after surgery. Furthermore, LAPPG could bring about significant improvement in total protein and hemoglobin compared to LADGBI at postoperative 2 years. Conclusion LAPPG obtains QOL as well as total protein and hemoglobin superiority and could be recommended to patients with EGC whose tumor located in the middle third of the stomach.

We conducted a longitudinal exploration of the relationship between anger rumination and interpersonal openness, which is an indigenous interpersonal trait in the Chinese cultural context. Participants were 942 undergraduate university students who completed a survey at 2 time points spaced 6 months apart. Structural equation modeling results showed that interpersonal openness at Time 1 negatively predicted anger rumination at Time 2. In addition, the results of hierarchical linear regression analysis showed that after controlling for the Big Five personality traits at Time 1, interpersonal openness at Time 1 negatively predicted anger rumination at Time 2. These results provide new evidence to suggest that interpersonal openness may be an interpersonal trait that is related to anger rumination. Theoretical and practical implications are discussed.

Conventional photosensitizers (PSs) often show poor tumor retention and are rapidly cleared from the bloodstream, which is one of the key hindrances to guarantee precise and efficient photodynamic therapy (PDT) in vivo. In this work, we present a photosensitizer assembly nanosystem that sharply enhances tumor retention up to ∼10 days. The PSs are synthesized by meso-substituting anthracene onto the BODIPY scaffold (AN-BDP), which then self-assemble into stable nanoparticles (AN-BDP NPs) with amphiphilic block copolymers due to the strong intermolecular π-π interaction of anthracene. Additionally, the incorporated anthracene excites the PSs, producing singlet oxygen under red light irradiation. Although AN-BDP NPs could completely suppress regular test size tumor (∼100 mm3 ) by one-time radiation, only 12% tumour growth inhibition rate was observed in the case of large size tumor (∼350 mm3 ) under the same conditions. Due to the long time tumor retention, AN-BDP NPs allows single-dose injection and three-time light treatments, resulting in an over 90% inhibition rate, much more efficient than single-time radiation of conventional clinically used PSs including chlorin (Ce6) and porphyrin with poor tumor retention. The results reveal the importance of long tumor retention time of PSs for efficient PDT, which can accelerate the clinical development of nanophotosensitizers. This article is protected by copyright. All rights reserved.

Background: Small bowel adenocarcinoma are relatively rare tumors of the digestive system. Due to the lack of specific screening methods, patients are often diagnosed at an advanced stage. At present, there is no specific surgical guidance and chemotherapy regimen for small bowel adenocarcinoma. Here, we report a rare small bowel adenocarcinoma case with mesenteric vascular embolization and microsatellite instability, in which palliative surgery combined with chemotherapy and anti-Programmed cell death protein 1(PD-1) therapy resulted in complete remission.Case Presentation: The patient was a 55-year-old man who was admitted for suspected small bowel adenocarcinoma combined with incomplete ileus, mesenteric vascular occlusion and distant metastasis. We performed palliative surgery to remove adenocarcinoma as well as relieve obstruction. Then according to the pathological and immunohistochemical results (Stage IV and microsatellite instability), we used XELOX regimen combined with anti-PD-1 therapy. In last 2 years follow up, this patient achieved complete remission.Conclusions: The possibility of small intestinal tumor should be considered in patients with mesenteric vascular obstruction. PD-1 blockade is an effective therapy for small bowel adenocarcinoma with microsatellite instability.

Monitoring the tumor oxygen level when implementing photodynamic therapy (PDT) on malignant cancer has vital significance but remains challenging yet. Herein, by structurally manipulating a 2,4-dimethylpyrrole-engineered asymmetric BODIPY scaffold with different kinds, numbers, and positions of halogen atoms, we rationally designed several monochromophore-based bifunctional photosensitizers, named BDPs (BDP-I, BDP-II, and BDP-III), with self-sensitized photooxidation characteristics for accurate oxygen reporting and photodynamic tumor ablation. We show that different ways of halogen regulation allow available tuning of BDPs' oxygen-dependent ratiometric fluorescence turn-ons upon light irradiation as well as type-II PDT efficiencies before and after self-sensitized photooxidation. Encouragingly, measuring the specific ratiometric signals of the most promising BDP-II enabled the direct observation of initial oxygen concentration in both living 4T1 cells and a tumor-bearing mice model, affording an alternative way for evaluating oxygen supplementation strategies. Meanwhile, the "always on" PDT effect of BDP-II ensured efficient tumor ablation via apoptosis. Our research was thus believed to be of instructive significance for future application of oxygen-related auxiliary strategies and the design of unimolecular multifunctional PDT agents for cancer precision therapy.

BackgroundMetastasis and/or recurrence are the primary cause in decreasing the survival time of gastric cancer patients who experienced radical operation. Among whom, patients with stage IIIb and IIIc are especially in high risk of metastasis and recurrence, result in a significant poor survival time than patients with earlier stages. Herbal medicines are natural substances that have been used for centuries in China, auricular acupressure and acupoints has shown promise in reducing side effects of chemotherapy，this traditional Chinese medicine collaborative model（TCMCM）has been studied in cancer, however, the specific effects have not been systematically evaluated. This study was designed to evaluate whether TCMCM can decrease adverse effects after chemotherapy and reduce the recurrence rate and metastasis in stage IIIb and IIIc gastric cancer. Method/designThis prospective，multicenter, randomized, open-label trail will recruit 260 patients with stage IIIb and IIIc gastric cancer who undergo radical surgery with D2 lymphadenectomy. Randomization to usual adjuvant chemotherapy or the intervention (TCMCM) with a 1:1 ratio will be used. Patients in the intervention group received an oral traditional Chinese formula, auricular acupressure and acupoints, all participants will be continuing to receive usual adjuvant chemotherapy. The primary outcome is 3-year disease free survival rate. Secondary outcomes include quality of life，side effects caused by chemotherapy and safety outcome measures. Assessments will be performed at Screening period and 4，8 cycles after adjuvant chemotherapy，9, 12, 18, 24,30 and 36 months after randomization, and adverse events will be recorded.In addition,biological samples will be collected for mechanism exploration studies. DiscussionThis will be the first clinical trial to evaluate the disease-free survival (DFS) and improvements in quality of life in patients of stage IIIb and IIIc gastric cancer receiving TCMCM, which may be used to formulate a standardized TCMCM plan. We are also performing this trial to assess the feasibility of a larger-scale clinical trial in the future. Trail registrationClinicalTrials.gov，NCT03607656. Registered on 1 July 2018.The final protocol version was V1.1.

Lipid droplets (LDs), an extremely important cellular organelle, are responsible for the storage of neutral lipids in multiple biological processes, which could be a potential target site for photodynamic therapy (PDT) of cancer. Herein, a lipid droplet–targeted photosensitizer (BODSeI) is developed, allowing for fluorescence imaging–guided PDT. Owing to the location of lipid droplets, BODSeI demonstrates enhanced PDT efficiency with an extremely low IC50 value (around 125 nM). Besides, BODSeI shows good biocompatibility and high photostability. Therefore, BODSeI is promising for droplet-location PDT, which may trigger wide interest for exploring the pathway of lipid droplet–location PDT.

BACKGROUND Alopecia areata is a hair loss disease associated with genetics, autoimmunity, and other factors. There is an intriguing link between alopecia areata and gut dysbiosis. Fecal microbiota transplantation (FMT) has been recommended to treat Clostridium difficile (previously known as Clostridioides difficile) infection, and has also shown potentials in the treatment of inflammatory bowel disease, irritable bowel syndrome, and non-alcohol fatty liver disease. CASE SUMMARY An 86-year-old man, with a history of sigmoid colon carcinoma, suffered from recurrent abdominal pain and distension, and diarrhea for six months, with inappetence. At admission, he was also diagnosed with depression. Upon physical examination, the patient presented with a 1.5 cm × 2.0 cm alopecia areata on his right occiput. Due to the negative results of laboratory testing, capsule endoscopy, and colonoscopy, the patient was diagnosed with noninfectious diarrhea, depressive disorder, and patchy alopecia areata. Considering that noninfectious diarrhea in the elderly patient was mainly caused by gut dysbiosis, he was given six rounds of FMT. His diarrhea improved remarkably one month after FMT, with improved appetite and disappearance of abdominal pain, distension, and depressive symptoms. Surprisingly, he reported new hair growth on the affected region of his scalp, with some of his white hair gradually turning to black, without taking any other therapies for alopecia areata before and after FMT. CONCLUSION FMT might act as a potential therapy for patients who suffer from alopecia areata. Large and well-designed studies are required to confirm the role of FMT in alopecia areata.

Background Displaced aggression is a specific form of attack prompted by rumination on anger experiences and revenge thought which might lead to expression of anger on innocent people. There is sufficient evidence demonstrating the potential role of agreeableness in reducing displaced aggression in theory. However, little is known about the neural basis of displaced aggression and how agreeableness and the underlying neural mechanisms link to displaced aggression. Methods In this investigation, we examined these issues on 123 college students by assessing resting-state brain activity (i.e. amplitude of low-frequency fluctuation, ALFF) and connectivity (i.e. resting-state functional connectivity, RSFC). Results Whole-brain correlation analysis revealed that a higher level of displaced aggression was linked with decreased ALFF in the left dorsomedial prefrontal cortex (dmPFC) and decreased RSFC between the left dmPFC and left ventromedial prefrontal cortex (vmPFC). Mediation analysis further revealed that left dmPFC activity and the left dmPFC–vmPFC connectivity mediated the relationship between agreeableness and displaced aggression, as well as agreeableness mediated the relation between left dmPFC activity and the left dmPFC–vmPFC connectivity and displaced aggression. Limitations Only ALFF and RSFC were used as indicators of brain function in this study. The two mediation models need to be further tested by longitudinal design or experimental methods in further studies. Conclusions This study suggested that dmPFC and vmPFC might be the functional neural markers of displaced aggression and provided two possible mediation models regarding the relationship among the resting-state brain activity and connectivity, agreeableness and displaced aggression.

The aim of this article was to review the roles of Helicobacter pylori-induced antralization in gastric carcinogenesis and its implications in clinical practice. A search of PubMed/PubMed Central, Web of Science, and China National Knowledge Infrastructure was performed in December 2018 to retrieve all literature related to antralization (or antralisation), pyloric (or pseudopyloric) glands, pyloric (or pseudopyloric) metaplasia, or pyloric (or pseudopyloric) gland metaplasia, and spasmolytic polypeptide-expressing metaplasia (or SPEM). Among the synonyms, antralization and SPEM, which are derived in the same mechanisms at the molecular, cellular and tissue levels, are more commonly used in recent studies. Antralization (or SPEM) is associated with H. pylori infection, atrophic gastritis and intestinal metaplasia, while H. pylori eradication may reverse antralization. It is proposed that H. pylori infection leads to inflammation in the gastric mucosa and apoptosis of the epithelial cells of the proximal stomach, including gastric incisura, body and fundus. The stem cells proliferate and transform into mucous cells and form antral-type mucosa (i.e. antralization). Subsequently, H. pylori-induced antralization, if not controlled, may develop into atrophic gastritis, intestinal metaplasia, dysplasia, and early intestinal-type gastric cancer. Although many biomarkers, including the spasmolytic polypeptide and mucin 6, are specifically expressed in the gastric mucosa with antralization, none of them are evaluated for the clinical diagnosis of antralization. H. pylori-induced antralization (or SPEM) is believed to be an initiating and reversible stage of gastric carcinogenesis. Identification of antralization would help make an early intervention to cease or even reverse the process toward the development of gastric cancer. Currently, the “gold standard” for diagnosing antralization is pathology, which is invasive and time consuming. A non-invasive and convenient method that accurately and specifically diagnoses antralization is urgently required.

Hepatitis C virus (HCV) infects at least 150 million people chronically worldwide. It is a major risk factor for cirrhosis, hepatocellular carcinoma, and death. Direct-acting antiviral therapy is very efficacious in treating HCV infection but it is inaccessible and unavailable in some developing countries. Therefore, searching for more effective and easily accessible regimens remains an urgent need. The aim of this article is to review the anti-HCV effects of herbal medicines from experimental to clinical evidence, and discuss current issues, hurdles and future perspectives for their application from bench to bedside. Numerous in vitro studies have indicated that many herbs work effectively in exerting anti-HCV activities. Yet, only a few animal experiments have been conducted that demonstrate the anti-HCV effects of these medicines; in addition, these results do not show an ability to eliminate the virus completely from the infected animals. Thus far, clinical trials have produced inconclusive anti-HCV results in terms of efficacy and safety, presumably due to the lack of the quality of methodologies used in the trials. In conclusion, despite apparent anti-HCV activities in vitro, clinical efficacy and safety of herbal medicines for the treatment of HCV infection have not been revealed convincingly. More animal studies using ideal models and more well-designed clinical trials with a larger sample sizes and longer treatment periods, taking the body habitus into consideration, are required to further assess the efficacy and safety of herbal medicines for HCV infection.

Aggression is one of the most serious social problems worldwide. The cognitive mechanisms of aggression have been frequently studied, and hostile attribution bias has been regarded as an important cognitive factor influencing the formation and development of aggression. However, the longitudinal relationship between hostile attribution and aggression among undergraduate students has not yet been tested, and the psychological mechanism underlying the effect of hostile attribution on aggression has not yet been explored. This study aimed to address these two issues through two studies. The Hostility subscale of the Word Sentence Association Paradigm for Hostility and the Buss-Perry Aggression Questionnaire were administered to 505 undergraduate students twice with an interval of 6 months in Study 1. The cross-lagged analyses demonstrated a reciprocal relationship between hostile attribution bias and aggression. Another 437 participants were recruited for Study 2. The analyses via structural equation modeling support the view that anger rumination plays a mediating role in the relationship between hostile attribution bias and aggression. This study expands our understanding regarding the relationship between hostile attribution bias and aggression and suggests an interaction between aggressive cognition and aggressive behavior. In addition, certain aggressive cognitive factors may predict other aggression-related cognitive factors.

Nonalcoholic fatty liver disease (NAFLD) is significantly on the rise, which will seriously affect human health; yet, there is no approved drug for the treatment of NAFLD currently. Recently, more and more studies have demonstrated that intestinal bacteria affect liver function through the gut-liver axis, and that the imbalance of intestinal bacterial composition is essential in the pathogenesis of NAFLD. Correcting intestinal bacterial imbalance, therefore, may prevent the development and attenuate the progression of NAFLD. Fecal microbiota transplantation (FMT) is considered the most effective method to correct intestinal bacteria imbalance, but its therapeutic role in NAFLD has not been established. Moreover, the potential molecular mechanisms of FMT for NAFLD have not been elucidated. This review paper summarizes the currently available experimental and clinical research results on the therapeutic effects of FMT for NAFLD. In addition, the underlying molecular mechanisms are proposed, which would provide theoretical support for FMT as a useful modality for the treatment of NAFLD.

The majority of research regarding hostile attribution bias focuses on its effect on aggression. However, little is known about the brain structure associated with trait hostile attribution bias and the mediating mechanism underlying this link. The current study uses voxel-based morphometry (VBM) to identify the brain regions related to individual differences in trait hostile attribution bias, measured by a Word Sentence Association Paradigm - Hostility in a sample of 176 undergraduate students. Subsequently, two mediation models with regard to brain structure, trait hostile attribution bias, and attitudes toward violence (measured by the Attitudes toward Violence Scale) were analyzed. The results reveal that trait hostile attribution bias is positively correlated with gray matter volume (GMV) in the left orbitofrontal cortex (OFC) and negatively associated with the left lingual gyrus (LG). Furthermore, attitudes toward violence acted as a mediator underlying the association between the left OFC volume and trait hostile attribution bias. Such bias also mediated the relationship between the left OFC and attitudes toward violence. We argue that attitudes toward violence and trait hostile attribution bias seem to predict each other, and the GMV in the left OFC may involve the underlying cognitive mechanism of the bidirectional relationship between the two variables. These results and ideas may shed light on the current understanding of the relationships of the brain's anatomical features, attitudes toward violence, and trait hostile attribution bias.

We try to develop an atlas-guided automatic planning (AGAP) approach and evaluate its feasibility and performance in rectal cancer intensity-modulated radiotherapy. The developed AGAP approach consisted of four independent modules: patient atlas, similar patient retrieval, beam morphing, and plan fine-tuning modules. The atlas was setup using anatomy and plan data from Pinnacle auto-planning (P-auto) plans. Given a new patient, the retrieval function searched the top similar patient by a generic Fourier descriptor algorithm and retrieved its plan information. The beam morphing function generated an initial plan for the new patient by morphing the beam aperture from the top similar patient plan. The beam aperture and calculated dose of the initial plan were used to guide the new plan optimization in the plan fine-tuning function. The AGAP approach was tested on 96 patients by the leave-one-out validation and plan quality was compared with the P-auto plans. The AGAP and P-auto plans had no statistical difference for target coverage and dose homogeneity in terms of V100%(p=0.76) and homogeneity index (HI)(p=0.073), respectively. The CI index showed they had a statistically significant difference. but the ΔCI was both 0.02 compared to the perfect CI index of 1. The AGAP approach reduced the bladder mean dose by 152.1cGy (p

Background and PurposeTo develop an artificial intelligence-based full-process solution for rectal cancer radiotherapy.Materials and MethodsA full-process solution that integrates autosegmentation and automatic treatment planning was developed under a single deep-learning framework. A convolutional neural network (CNN) was used to generate segmentations of the target and the organs at risk (OAR) as well as dose distribution. A script in Pinnacle that simulates the treatment planning process was used to execute plan optimization. A total of 172 rectal cancer patients were used for model training, and 18 patients were used for model validation. Another 40 rectal cancer patients were used for an end-to-end evaluation for both autosegmentation and treatment planning. The PTV and OAR segmentation was compared with manual segmentation. The planning results was evaluated by both objective and subjective assessment.ResultsThe total time for full-process planning without contour modification was 7 min, and an additional 15 min may require for contour modification and re-optimization. The PTV DICE similarity coefficient was greater than 0.85 for all 40 patients in the evaluation dataset while the DICE indices of the OARs also indicated good performance. There were no significant differences between the auto plans and manual plans. The physician accepted 80% of the auto plans without any further operation.ConclusionWe developed a deep learning-based automatic solution for rectal cancer treatment that can improve the efficiency of treatment planning.

Rationale: There are many treatments for chronic hemorrhagic radiation colorectal inflammation, but only a few treatments are supported by high-quality research evidence. Studies have shown that the occurrence and development of radiation proctitis are closely associated with the intestinal flora. Animal studies have indicated that faecal microbiota transplantation (FMT) can improve radiation enteropathy in a mouse model. Patient concerns: A 45-year-old female patient suffered from recurrent hematochezia and diarrhea for half a year after radiotherapy and underwent recurrent transfusion treatments. Colonoscopy showed obvious congestion of the sigmoid colon and rectal mucosa, a smooth surface, and bleeding that was easily induced by touch, which are consistent with radiation proctitis. The pathological findings revealed chronic mucosal inflammation. The magnetic resonance imaging examination of the pelvic cavity with a plain scan and enhancement showed changes after radiotherapy and chemotherapy, and no obvious tumor recurrence or metastasis was found. The laboratory examinations excluded pathogen infection. Diagnoses: Based on the history and examinations, the final diagnosis of this patient was chronic hemorrhagic radiation proctitis. Interventions: The patient was treated with a total of 4 individual courses of FMT. Outcomes: After the six-month follow-up, her hematochezia, abdominal pain and diarrhea were relieved. Furthermore, 16S rRNA sequencing of the feces showed that the intestinal bacterial composition of the patient obviously changed after FMT and became similar to that of the donors. Lessons: This case report shows that FMT can relieve the symptoms of hematochezia and diarrhea by changing the bacterial community structure in patients with chronic hemorrhagic radiation proctitis.

Aims: This study aims to evaluate and validate a simple quantitative ultrasound (US) method for determining the hepatic fat content (HFC) based on the combination of quantitative US hepatic/renal ratio (US-HRR) and quantitative US hepatic echo-intensity attenuation rate (US-HAR) as compared with [1H]-magnetic resonance spectroscopy (1H-MRS).Material and methods: There were a total of 242 subjects recruited in the present study. All subjects were examined for HFC by quantitative US and 1H-MRS methods. The QUS-HRR and QUS-HAR were calculated from ordinary ultrasound images of liver and kidney with a triple modality 3D abdominal phantom using the Image J software.Results: The results found that US-HRR and US-HAR correlated with 1H-MRS HFC (US-HRR: r=0.946, p

BACKGROUND: Coronavirus disease 2019 (COVID-19) is often accompanied by gastrointestinal symptoms, which is related to gut microbiota dysbiosis (GMD). Whether washed microbiota transplantation (WMT) is effective in COVID-19 patients suspected with GMD by restoring gut microbiota is unknown. This study is designed to explore the efficacy and safety of WMT in COVID-19 patients suspected with GMD.METHODS: COVID-19 patients suspected with GMD will be randomly divided to receive routine treatment (group A) or receive routine treatment and WMT (group B). The frequency of WMT will be once a day for three consecutive days. Nucleic acid test, imaging examination, and tests related to organ functions, homeostasis, inflammatory response, intestinal barrier function and immunity will be performed at admission, 1, and 2 weeks after treatment and on the day of discharge. The clinical efficacy and safety of WMT in COVD-19 suspected with GMD and the effects of WMT on the organ function, homeostasis, inflammatory response, intestinal barrier function and immunity of the patients will be evaluated. The primary outcome will be the clinical efficacy, as reflected by the SARS-Cov-2 infection status, gastrointestinal symptoms and the recovery of the disease. The secondary outcomes will be the effects of WMT on the organ function, homeostasis, inflammatory response, intestinal barrier function and immunity of the patients, as well as occurrence of adverse events during WMT.DISCUSSION: In the proposed protocol, WMT is expected to be efficacious and safe for the treatment of COVID-19 patients suspected with GMD, and the therapeutic effect is expected to be associated with the improvement of intestinal barrier function, inflammatory response and immunity. Findings from this study may open up a new way for the prevention and treatment of COVID-19 suspected with GMD.TRIAL REGISTRATION: Chinese Clinical Trial Registry – URL: http://www.chictr.org.cn/index.aspx. Registration number: ChiCTR2000032737. Registered 9 May 2020.

Background: Gut dysbiosis has been reported to be closely associated with gout. Fecal microbiota transplantation (FMT) has been considered as an effective way to restore the balance of gut microbiota. We aimed to evaluate the effects of FMT on serum uric acid levels, gout symptoms and the intestinal barrier function in patients with acute and recurrent gout. Methods: We performed a pilot study of FMT for acute and recurrent gout. The primary outcome was the changes in serum uric acid level on day 28 post-FMT and in gout symptoms by one year. The secondary outcomes included the changes in levels of urine uric acid, diamine oxidase (DAO), D-lactic acid and endotoxin on day 28 post-FMT. The levels of DAO, D-lactic acid and endotoxin were assessed by enzyme assay. Results: Eleven patients received FMT treatment. All the patients had a reduction in serum uric acid levels after FMT treatment ( P < 0.05), accompanied with a decrease in the frequency and duration time of acute gout flares. The levels of DAO, D-lactic acid and endotoxin, reflecting the intestinal barrier function, were higher in patients with gout than in healthy donors ( P < 0.05). After FMT treatment, the levels of DAO and endotoxin decreased ( P < 0.05). Conclusions: Our findings demonstrate that FMT is effective for reducing serum uric acid levels and improving gout symptoms in patients with gout; FMT contributes to improve the impaired intestinal barrier function of the patients.

Background hsa_circ_0000826 has been previously linked to CRC through the competing endogenous RNA network; however, the upstream driver of hsa_circ_0000826 elevation remains unknown. In this study, we aim to elucidate the effect of hypoxia‐induced hsa_circ_0000826 on CRC tumorigenesis and metastasis. Methods RNA scope assay was used to evaluate the expression of hsa_circ_0000826 in CRC cells under hypoxia condition. The effects of hsa_circ_0000826 on phenotypes of CRC cells were evaluated through cell migration and invasion assay. The nude, AOM‐DSS model mice and APCMin /+ mice were used to investigate the relationship between circ_0000826, hypoxia, and CRC in mice. A total of 100 CRC tissue samples, as well as the paired adjacent tissues, were collected, and qRT‐PCR assay was used to detect the expression of hsa_circ_0000826 in these samples. Results Hypoxia‐induced hsa_circ_0000826 overexpression can increase the malignant phenotypes, tumor formation, and metastasis capability of CRC cells in vitro. mmu_circ_0000826 levels were significantly increased in the CRC tissues from AOM‐DSS and APC mice model under hypoxia conditions. Further, the hypoxia‐induced upregulation of mmu_circ_0000826 can also promote CRC tumorigenesis and liver metastasis in vivo. The expression of hsa_circ_0000826 in serum was significantly increased in CRC tissues in 100‐pair of CRC and according to the adjacent normal tissues by qRT‐PCR assays. Moreover, the expression levels of hsa_circ_0000826 in serum of patient with liver metastasis were significantly increased than those without metastasis. Conclusion Our results suggested that hsa_circ_0000826 was induced by the hypoxia in CRC, which can be a potential biomarker of CRC liver metastasis.

Background: Gastric cancer (GC) remains a refractory cancer particularly in Eastern Asia. Large tumor suppressor kinases 1/2 (LATS1/2) are core members of the Hippo pathway. The role of LATS1/2 in the prognosis of different subtypes of advanced gastric cancer and its relationship with the tumor immune microenvironment in GC remain unknown. Exploring the role of LATS1/2 in GC might provide potential immunotherapeutic approaches for treating GC. Methods: Four hundred and ninety surgically resected primary GC samples were assessed for LATS1/2, CD8, FOXP3, and CD163. Correlations between LATS1/2 expression and immune-related markers were investigated and the prognoses of patients with different GC subtypes were analyzed. Results: CD8 and CD163 appeared to be favorable and adverse prognostic factors, respectively. LATS1/2 and FOXP3 did not predict patients' overall survival. However, in microsatellite-stable GC patients, high LATS1/2 and FOXP3 expression and low CD8 expression predicted poor prognoses. Furthermore, high LATS1/2 expression was significantly correlated with decreased CD8 and increased FOXP3. Combined analysis of LATS1/2, CD8, and FOXP3 had better prognostic accuracy than did each marker individually. Conclusions: Different biological molecules can predict the prognoses of different types of GC patients. LATS1/2, core kinases in the Hippo pathway, are closely related to CD8 and FOXP3. Further understanding the mechanisms of LATS1/2 in CD8+ T cells and FOXP3+ Treg cells provides further theoretical basis and potential targets for GC immunotherapy.

Background Previous literatures have implied that the liver fat deposition plays a crucial role in the development and progression of insulin resistance. In the present study, we aimed to investigate the association of liver fat content (LFC) with glucose metabolism status in the population of newly diagnosed type 2 diabetes mellitus (nT2DM), prediabetes mellitus (PDM) and normal controls (NC), and assessing if the LFC could as an indicator for the prediction of T2DM. Methods A total of 242 subjects (including 141 nT2DM patients, 48 PDM subjects and 53 NC) were enrolled. The levels of LFC were quantified by using the proton magnetic resonance spectroscopy ([1H]-MRS) technique. Clinical and laboratory parameters of study subjects were collected by medical records and biochemical detection. One-way ANOVA or nonparametric test (Kruskal–Wallis) was applied for intergroup comparisons; intergroup comparison was performed in using of Bonferroni multiple-significance-test correction. Results There were significantly increased LFC levels in nT2DM (14.72% ± 6.37%) than in PDM (9.62% ± 4.41%) and that of NC groups (5.11% ± 3.66%) (all p AUC, CP30/G30 AUC, Ins AUC/G AUC, CP AUC/G AUC, homeostatic model assessment for β-cell function index (HOMA-β) and matsuda insulin sensitivity index (Matsuda ISI). Multilinear regression analysis showed that LFC, body mass index (BMI) and diastolic blood pressure (DBP) contributed for the prediction of HOMA-IR, and total cholesterol (TC), age, waist circumference (WC) and low-density lipoprotein cholesterol (LDL-C) were the significant contributors for HOMA-β. Conclusions Our study revealed an increased LFC level and prevalence of NAFLD in nT2DM than in PDM and that of NC groups, the increase of LFC was closely associated with insulin resistance and impaired glucose metabolism status, may be regarded as potential indicator contributing to the development and progression of T2DM.

This paper discusses issues regarding cultivating the creative ability of Chinese industrial design undergraduate students in the teaching and learning process. First, we review literature explores how ""creativity"" is understood within the context of Chin

Objective This study aimed to study the effects of laparoscopic-assisted radical gastrectomy (LAG) and open radical gastrectomy (OG) on immune function and inflammatory factors in patients with early gastric cancer. Methods Seventy-five patients with pT1N0M0 gastric cancer in Ren Ji Hospital from August 2017 to January 2018 were studied. Lymphocytes subsets and interleukins were compared preoperatively and on the third postoperative day (POD3) and seventh postoperative day (POD7). Results There were no significant differences in age, sex, body mass index, duration of the operation, estimated blood loss, total gastrectomy rate, postoperative first fluid diet, and the levels of preoperative lymphocytes subsets and interleukins between the two groups. The number of CD4+ T cells and the CD4+/CD8+ ratio in the LAG group were significantly higher than those in the OG group on POD3. However, the number of CD8+ T cells, and interleukin-6 and interleukin-8 levels in the LAG group were significantly lower than those in the OG group on POD3. Conclusions Laparoscopy can effectively reduce the levels of inflammatory factors and has less effect on the immune system than OG.

Klebsiella variicola B16, a microbial bioflocculant (MBF-B16)-producing bacteria, was isolated and identified by its 16S rRNA sequence, biochemical properties, and physiological characteristics. The effects of culture conditions on MBF-B16 production, including carbon source, nitrogen source, C/N ratio, initial pH, and culture temperature, were investigated in this study. Results showed that 6.96 g of MBF-B16 could be extracted from a 1-L culture broth under optimized conditions. Chemical analysis showed that polysaccharide and protein were the main components. The neutral sugar consisted of galactose only, which was proposed in Klebsiella genus for the first time. In addition, a composite flocculant (CF) that contains polyaluminum ferric chloride (PAFC) and MBF-B16 for the removal of turbidity and SS in drinking water was optimized by response surface methodology. CF could reduce PAFC dosage by about 56.2–72%. Charge neutralization and adsorption bridging effect were the primary flocculation mechanisms.

Although photodynamic therapy (PDT) is a promising approach for cancer therapy, most existing photosensitizers lack selectivity for tumor cells and the overexpressed glutathione (GSH) in tumor cells reduces the PDT efficiency. Therefore, designing photosensitizers that can be selectively activated within tumor cells and combine PDT with other therapeutic modalities represents a route for precise and efficient anticancer treatment. Herein, we report an organic activatable photosensitizer, CyI-DNBS, bearing 2,4-dinitrobenzenesulfonate (DNBS) as the cage group. CyI-DNBS can be uptaken by cancer cells after which the cage group is selectively removed by the intracellular GSH, resulting in the generation of SO2 for gas therapy. The reaction also releases the activated photosensitizer, CyI-OH, that can produce singlet oxygen (1 O2 ) under red light irradiation. Therefore, CyI-DNBS targets cancer cells for both photodynamic and SO2 gas therapy treatments. The activatable photosensitizer provides a new approach for PDT and SO2 gas synergistic therapy and demonstrates excellent anticancer effect in vivo. This article is protected by copyright. All rights reserved.