A multi-omics analysis-based model to predict the prognosis of low-grade gliomas.

Lower-grade gliomas (LGGs) exhibit highly variable clinical behaviors, while classic histology characteristics cannot accurately reflect the authentic biological behaviors, clinical outcomes, and prognosis of LGGs. In this study, we carried out analyses of whole exome sequencing, RNA sequencing and DNA methylation in primary vs. recurrent LGG samples, and also combined the multi-omics data to construct a prognostic prediction model. TCGA-LGG dataset was searched for LGG samples. 523 samples were used for whole exome sequencing analysis, 532 for transcriptional analysis, and 529 for DNA methylation analysis. LASSO regression was used to screen genes with significant association with LGG survival from the frequently mutated genes, differentially expressed genes, and differentially methylated genes, whereby a prediction model for prognosis of LGG was further constructed and validated. The most frequently mutated diver genes in LGGs were IDH1 (77%), TP53 (48%), ATRX (37%), etc. Top significantly up-regulated genes were C6orf15, DAO, MEOX2, etc., and top significantly down-regulated genes were DMBX1, GPR50, HMX2, etc. 2077 genes were more and 299 were less methylated in recurrent vs. primary LGG samples. Thirty-nine genes from the above analysis were included to establish a prediction model of survival, which showed that the high-score group had a very significantly shorter survival than the low-score group in both training and testing sets. ROC analysis showed that AUC was 0.817 for the training set and 0.819 for the testing set. This study will be beneficial to accurately predict the survival of LGGs to identify patients with poor prognosis to take specific treatment as early, which will help improve the treatment outcomes and prognosis of LGG.

Assessing watershed-scale impacts of best management practices and elevated atmospheric carbon dioxide concentrations on water yield.

Changes in water yield are influenced by many intersecting biophysical elements, including climate, on-land best management practices, and landcover. Large-scale reductions in water yield may present a significant threat to water supplies globally. Many of these intersecting factors are intercorrelated and confounded, making it challenging to separate the factors' individual contributions to shaping local streamflow dynamics. Comprehensive hydrological models constructed based on a well-established understanding of biophysical processes are often employed to address these matters. However, these models rarely incorporate all relevant factors influencing local hydrological processes, due to the reliance of these models on the latest, albeit limited, state-of-the-art research. For instance, complexities inherent in watershed hydrology, which involve multilayered interactions among potentially many biophysical factors, leave the direct analysis of subtle impacts on water yields measured in-situ largely intractable. Therefore, we propose an innovative approach to assess impacts of elevated atmospheric CO2 concentrations and flow diversion terraces (FDTs) on stream discharge rates at the watershed scale. Initially, we use a comprehensive hydrological model to account for the impacts of major climatic and landuse/landcover factors on changes in field-acquired measurements of water yield. Next, we employ conventional and advanced statistical methods to decompose the residuals of model predictions to facilitate the identification of subtle influences promoted by increases in atmospheric CO2 concentrations and the application of FDTs in an agriculture-dominated watershed. Through this innovative approach, we find that FDTs contributed to a watershed-wide, net water-yield reduction of 188.0 mm (or 28.9 %) from 1992 to 2014. Ongoing increases in ambient CO2 concentrations, which are responsible for an overall reduction in a watershed-level assessment of stomatal conductance, have led to a minor increase in stream discharge rates during the same 23-year period, i.e., 0.45 mm of water yield per year, or 1.6 % overall. Streamflow reductions explicitly caused by regional warming in the area alone, on account of increased evapotranspiration, may be overestimated due to the opposing, synergistic effects on water yield associated with CO2-enrichment of the lower atmosphere and the annual application of FDTs.

Individualized intervention based on a preparation-related prediction model improves adequacy of bowel preparation: A prospective, multi-center, randomized, controlled study.

AIMS: An easy-to-use preparation-related model (PRM) predicting inadequate bowel preparation (BP) was developed and proved superior to traditional models in our previous study. Here we aimed to investigate whether PRM-based individualized intervention can improve BP adequacy. METHODS: Patients undergoing morning colonoscopy were prospectively enrolled in 5 endoscopic centers in China. After standard BP of split-dose polyethylene glycol (PEG) was completed, patients were randomized (1:1) to the individualized group or standard group. High-risk patients predicted by PRM score ≥3 were instructed to drink an additional 1.5 L PEG in the individualized group while not in standard group. The primary endpoint was the rate of adequate BP, defined by segmental Boston bowel preparation scale ≥2. Secondary outcomes included adenoma detection rate (ADR) and adverse events. RESULTS: 900 patients were randomly allocated to the individualized group (n = 449) and the control (n = 451). Baseline characteristics were similar between the two groups. The rates of high-risk patients were 19.6 % in individualized group and 19.7 % in standard group. In intention-to-treat analysis, adequate BP was 91.8 % in individualized group and 84.7 % in the standard group (p = 0.001). Among high-risk patients, adequate BP rate was 94.3 % in individualized group and 49.3 % in standard group (p < 0.001), and ADR were 40.9 % vs 16.9 %, respectively (p < 0.001). No significant differences were found regarding the adverse events and willingness to repeat BP (all p >0.05). CONCLUSIONS: The individualized intervention using an additional dose of PEG to high-risk patients predicted by PRM, significantly improved BP quality. The intervention significantly improved ADR in high-risk patients. (ClinicalTrials.gov number: NCT04434625).

Transcutaneous Auricular Vagal Nerve Stimulation Is Effective for the Treatment of Functional Dyspepsia: A Multicenter, Randomized Controlled Study.

INTRODUCTION: Vagal nerve stimulation (VNS) can be used to modulate gastrointestinal motility, inflammation, and nociception. However, it remains unclear whether VNS is effective in adult patients with functional dyspepsia (FD). We investigated the effectiveness of transcutaneous auricular VNS (taVNS) in patients with FD. METHODS: Consecutive patients with FD meeting Rome IV criteria with modified FD Symptom Diary score ≥10 were enrolled. Patients were randomly allocated to 10-Hz taVNS (V10 group), 25-Hz taVNS (V25 group), or sham group, with 30 minutes of treatment twice a day for 4 weeks. The primary outcome was the response rate at week 4, defined as the proportion of patients whose modified FD Symptom Diary score was reduced ≥5 when compared with the baseline. Secondary outcomes included adequate relief rate and adverse events. RESULTS: A total of 300 patients were randomized to V10 (n = 101), V25 (n = 99), and sham groups (n = 100). After 4 weeks of treatment, V10 and V25 groups had a higher response rate (81.2% vs 75.9% vs 47%, both P < 0.001) and adequate relief rate (85.1% vs 80.8% vs 67%, both P < 0.05) compared with the sham group. There was no significant difference between V10 and V25 in response rate and adequate relief rate (both P > 0.05). The efficacy of taVNS (both 10 and 25 Hz) lasted at week 8 and week 12 during follow-up period. Adverse events were all mild and comparable among the 3 groups (1%-3%). DISCUSSION: Our study firstly showed that 4-week taVNS (both 10 and 25 Hz) was effective and safe for the treatment of adult FD ( clinicaltrials.gov number: NCT04668534).

DNMT1 expression partially dictates 5-Azacytidine sensitivity and correlates with RAS/MEK/ERK activity in gastric cancer cells.

Though DNMTs inhibitors were widely used in myelodysplastic syndrome and leukaemia, their application in solid tumours has been limited by low response rate and lack of optimal combination strategies. In gastric cancer (GC), the therapeutic implication of KRAS mutation or MEK/ERK activation for combinational use of DNMTs inhibitors with MEK/ERK inhibitors remains elusive. In this study, stable knockdown of DNMT1 expression by lentiviral transfection led to decreased sensitivity of GC cells to 5-Azacytidine. KRAS knockdown in KRAS mutant GC cells or the MEK/ERK activation by EGF stimulation in GC cells increased DNMT1 expression, while inhibition of MEK/ERK activity by Selumetinib led to decreased DNMT1 expression. 5-Azacytidine treatment, which led to dramatic decline of DNMTs protein levels and increased activity of MEK/ERK pathway, altered the activity of MEK/ERK inhibitor Selumetinib on GC cells. Both RAS-dependent gene expression signature and expression levels of multiple MEK/ERK-dependent genes were correlated with DNMT1 expression in TCGA stomach cancer samples. In conclusion, DNMT1 expression partially dictates 5-Azacytidine sensitivity and correlates with RAS/MEK/ERK activity in GC cells. Combining DNMTs inhibitor with MEK/ERK inhibitor might be a promising strategy for patients with GC.[Figure: see text].

Clinical and virological features of asymptomatic and mild symptomatic patients with SARS-CoV-2 Omicron infection at Shanghai Fangcang shelter hospital.

OBJECTIVE: The objective of this study is to evaluate and compare clinical and virological characteristics of asymptomatic and mild symptomatic patients of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2.2 variant infection and identify risk factors associated with the prolonged viral negative conversion duration. METHODS: We conducted a retrospective observational study in a Shanghai (China) Fangcang shelter hospital from April 9 to May 17, 2022. The patient-related demographic or clinical data were retrospectively recorded. Comparisons of demographic and clinical characteristics between asymptomatic and mild-symptomatic patients were performed. Cox regression was performed to identify the risk factors of prolonged viral negative conversion duration. RESULTS: A total of 551 patients confirmed with SARS-CoV-2 Omicron variant infection were enrolled in the study. Of these, 297 patients (53.9%) were asymptomatic and 254 patients (46.1%) had mild symptoms. When comparing the clinical and virological characteristics between the asymptomatic and mild symptomatic groups, several clinical parameters, including age, gender, time to viral clearance from the first positive swab, chronic comorbidities, and vaccination dose did not show statistically significant differences. In mild symptomatic patients, the median viral negative conversion duration (NCD) was 7 days (interquartile range [IQR]: 5-9), which was comparable to the median of 7 days (IQR: 5-10) in asymptomatic patients (p = .943). Multivariate Cox analysis revealed that patients age ≥ 60 years had a significantly higher hazard ratio (HR) for prolonged viral NCD (HR: 1.313; 95% confidence interval: 1.014-1.701, p = .039). CONCLUSION: Asymptomatic and symptomatic patients with non-severe SARS-CoV-2 Omicron BA.2.2 variant infection have similar clinical features and virological courses. Old age was an independent risk factor for prolonged SARS-CoV-2 conversion time.

Effects of different doses of dopamine receptor agonist pramipexole on neurobehaviors and changes of mitochondrial membrane potentials in rats with global cerebral ischemia-reperfusion injury.

OBJECTIVE: To explore the effects of different doses of dopamine receptor agonist pramipexole on neurobehaviors and changes of mitochondrial membrane potential in rats with global cerebral ischemia-reperfusion injury. METHODS: A total of 75 SPF Sprague-Dawley male rats were randomly divided into sham group (n=20), model group (n=20), pramipexole administration group (n=35). The rat model of global cerebral ischemia-reperfusion injury was prepared by the modified Pulsinelli's four-vessel occlusion method. Pramipexole administration group was administered intraperitoneally in rats with global cerebral ischemia-reperfusion injury at different doses of pramipexole 0.25 mg/kg, 0.5 mg/kg, 1 mg/kg, 2 mg/kg, once a day for 14 consecutive days. Based on the results of modified neurological severity scores, open field test and morphology by Nissl's staining to determine the optimal dose of pramipexole. Mitochondrial membrane potential in the optimal dose of pramipexole administration group were measured by the JC-1 fluorescent probe staining method. RESULTS: 1. Different doses of pramipexole 0.25 mg/kg, 0.5 mg/kg, 1 mg/kg, and 2 mg/kg, were used as drug administration in rats with global cerebral ischemia-reperfusion injury for 14 consecutive days, and we found that all four doses of pramipexole could improve the modified neurological severity scores of rats with global cerebral ischemia-reperfusion injury to varying degrees, but only 0.5 mg/kg pramipexole at 1, 3, 7 and 14 days consistently reduced modified neurological severity scores and improved neurological function in rats with global cerebral ischemia-reperfusion injury. In the open-field test, only 0.5 mg/kg pramipexole increased the number of entries into the central zone, duration spent in the central zone, total distance travelled in the open field and average velocity, which improved the spontaneous activities and reduced anxiety and depression of rats with global cerebral ischemia-reperfusion injury. 2. Different doses of pramipexole 0.25 mg/kg, 0.5 mg/kg, 1 mg/kg, and 2 mg/kg for 14 consecutive days significantly increased the number of surviving neurons in the hippocampal CA1 subfield in rats with global cerebral ischemia-reperfusion injury to varying degrees. Based on these results, we tentatively found that 0.5 mg/kg pramipexole may be the optimal dose in all of the above. 3. We found that 0.5 mg/kg pramipexole significantly increased the mitochondrial membrane potential in rats after global cerebral ischemia-reperfusion injury. CONCLUSION: Different doses of dopamine receptor agonist pramipexole improved neurological function of rats with global cerebral ischemia-reperfusion injury to varying degrees, and 0.5 mg/kg pramipexole may be the optimal dose in all of the above. Pramipexole may produce neuroprotective effects by protecting neurons in the hippocampus and improving the mitochondrial membrane potential after global cerebral ischemia-reperfusion injury.

Prolonged cannulation time is an independent risk factor for moderate-to-severe post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis: a large cohort study.

Background: Moderate-to-severe post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis contributes to most of the poor outcomes of patients with post-ERCP pancreatitis (PEP). However, it remains unclear which part of the patient is more vulnerable to moderate-to-severe PEP (MS PEP). In this study, we aimed to identify the risk factors independently associated with MS PEP. Methods: Consecutive patients with native papilla who had undergone ERCP were included in this study. The patient-related and procedure-related variables were retrieved from a prospectively maintained ERCP database. The primary outcome was the incidence of PEP. MS PEP was defined as a prolonged hospital stay of ≥4 days (as per the Cotton criteria) or the presence of organ failure (as per the revised Atlanta criteria). A logistic regression analysis was conducted to identify the risk factors. Results: A total of 6,944 patients with native papilla who had undergone elective ERCP from January 2010 to February 2022 were included in this study. Among these 6,944 patients, 362 (5.2%) patients developed PEP. Among these 362 patients, 76 (1.1%) or 17 (0.2%) had MS PEP as per the Cotton criteria and the revised Atlanta criteria, respectively. The logistic analysis revealed that the independent risk factors for overall and mild PEP were similar, and included being female and inadvertent pancreatic duct (PD) cannulation. A total cannulation time >15 min was also found to be an independent risk factor for MS PEP as defined by both the Cotton criteria and the revised Atlanta criteria. Conclusions: This study found that female patients and those who had inadvertent PD cannulation were at risk of mild PEP. A total cannulation time >15 min was also found to be a risk factor for developing MS PEP.

Analysis of clinical diagnosis and treatment of intestinal volvulus.

BACKGROUND: The aim of this study is to investigate the clinical characteristics and treatment experience of intestinal volvulus, and to analyze the incidence of adverse events and related risk factors of intestinal volvulus. METHODS: Thirty patients with intestinal volvulus admitted to the Digestive Emergency Department of Xijing Hospital from January 2015 to December 2020 were selected. The clinical manifestations, laboratory tests, treatment and prognosis were retrospectively analyzed. RESULTS: A total of 30 patients with volvulus were enrolled in this study, including 23 males (76.7%), with a median age of 52 years (33-66 years). The main clinical manifestations were abdominal pain in 30 cases (100%), nausea and vomiting in 20 cases (67.7%), cessation of exhaust and defecation in 24 cases (80%), and fever in 11 cases (36.7%). The positions of intestinal volvulus were jejunum in 11 cases (36.7%), ileum and ileocecal in 10 cases (33.3%), sigmoid colon in 9 cases (30%). All 30 patients received surgical treatment. Among the 30 patients underwent surgery, 11 patients developed intestinal necrosis. We found that the longer the disease duration (> 24 h), the higher the incidence of intestinal necrosis, and the higher the incidence of ascites, white blood cell count and neutrophil ratio in the intestinal necrosis group were significantly higher than those in the non-intestinal necrosis group (p < 0.05). After treatment, 1 patient died of septic shock after operation, and 2 patients with recurrent volvulus were followed up within 1 year. The overall cure rate was 90%, the mortality rate was 3.3%, and the recurrence rate was 6.6%. CONCLUSION: Laboratory examination, abdominal CT and dual-source CT are very important for the diagnosis of volvulus in patients with abdominal pain as the main symptom. Increased white blood cell count, neutrophil ratio, ascites and long course of disease are important for predicting intestinal volvulus accompanied by intestinal necrosis. Early diagnosis and timely intervention can save lives and prevent serious complications.

Low-dose of magnesium sulfate solution was not inferior to standard regime of polyethylene glycol for bowel preparation in elderly patients: a randomized, controlled study.

BACKGROUND: Large polyethylene glycol (PEG) is a standard regimen for bowel preparation. However, elderly patients suffered from adverse events. This study was to compare the efficacy and safety of oral magnesium sulfate solution (MSS) vs standard PEG in elderly patients undergoing colonoscopy. METHODS: Elderly patients aged 60-90 years, from two endoscopic centers, were enrolled in China. Patients were randomized to take a low dose of MSS or a standard PEG regime in a split-dose regime. The primary endpoint was the proportion of patients with adequate bowel preparation, which was defined as the total Boston Bowel Preparation Scale (BBPS) ≥6 and each segmental BBPS was ≥2. Secondary outcomes included adenoma detection rate (ADR), safety, adverse events, cecal intubation rate, willingness to repeat BP, and so on. RESULTS: 1174 elderly patients were randomly allocated to the MSS group (n = 588) or the standard group (n = 586). Adequate BP was achieved in 94.0% of patients in the MSS group and 92.5% in the control (p = .287). ADR was also comparable between the two groups (43.0% and 39.9%, p = .282). Compared with the standard group, MSS group reported less abdominal discomfort (1.7% vs 6.0%), less nausea (13.6% vs 21.0%) and vomiting (1.2% vs 4.2%). The change in serum potassium levels after preparation in the standard group was significantly lower than that in the MSS group (-0.19 ± 0.08 vs -0.41 ± 0.11, p = .037). CONCLUSIONS: Low dose of MSS was not inferior to the standard PEG regime in terms of bowel preparation quality for elderly patients. Low-dose MSS offered fewer adverse events and better tolerability. It is a preferable choice for the elderly to undergo bowel preparation for colonoscopy. CLINICAL TRIAL REGISTRATION NUMBER: NCT04948567.

Temporal heterogeneity in photosystem II photochemistry in Artemisia ordosica under a fluctuating desert environment.

Acclimation strategies in xerophytic plants to stressed environmental conditions vary with temporal scales. Our understanding of environmentally-induced variation in photosystem II (PSII) processes as a function of temporal scales is limited, as most studies have thus far been based on short-term, laboratory-controlled experiments. In a study of PSII processes, we acquired near-continuous, field-based measurements of PSII-energy partitioning in a dominant desert-shrub species, namely Artemisia ordosica, over a six-year period from 2012-2017. Continuous-wavelet transformation (CWT) and wavelet coherence analyses (WTC) were employed to examine the role of environmental variables in controlling the variation in the three main PSII-energy allocation pathways, i.e., photochemical efficiency and regulated and non-regulated thermal dissipation, i.e., Φ PSII, Φ NPQ, and Φ NO, respectively, across a time-frequency domain from hours to years. Convergent cross mapping (CCM) was subsequently used to isolate cause-and-effect interactions in PSII-energy partitioning response. The CWT method revealed that the three PSII-energy allocation pathways all had distinct daily periodicities, oscillating abruptly at intermediate timescales from days to weeks. On a diurnal scale, WTC revealed that all three pathways were influenced by photosynthetically active radiation (PAR), air temperature (T a), and vapor pressure deficit (VPD). By comparing associated time lags for the three forms of energy partitioning at diurnal scales, revealed that the sensitivity of response was more acutely influenced by PAR, declining thereafter with the other environmental variables, such that the order of influence was greatest for T a, followed by VPD, and then soil water content (SWC). PSII-energy partitioning on a seasonal scale, in contrast, displayed greater variability among the different environmental variables, e.g., Φ PSII and Φ NO being more predisposed to changes in T a, and Φ NPQ to changes in VPD. CCM confirmed the causal relationship between pairings of PSII-energy allocation pathways, according to shrub phenology. A. ordosica is shown to have an innate ability to (i) repair damaged PSII-photochemical apparatus (maximum quantum yield of PSII photochemistry, with F v/F m > 0.78), and (ii) acclimatize to excessive PAR, dry-air conditions, and prolonged drought. A. ordosica is relatively sensitive to extreme temperature and exhibits photoinhibition.

Superiority of a preparation-related model for predicting inadequate bowel preparation in patients undergoing colonoscopy: A multicenter prospective study.

BACKGROUND AND AIM: Three models based on patient-related factors have been developed to predict inadequate bowel preparation (BP). However, the performance of the models seems suboptimal. This study aimed to develop a novel preparation-related model and compare it with the available patient-related models. METHODS: Patients receiving standard BP were prospectively enrolled from five endoscopic centers. Patient-related and preparation-related factors for inadequate BP (defined by segmental Boston Bowel Preparation Scale score < 2) were identified by logistic regression. A preparation-related model was derived and internally validated in 906 patients. The comparisons of models were assessed by discrimination and calibration. The preparation-related model was also externally validated. RESULTS: Several patient-related factors (male and American Society of Anesthesiologists Physical Status Classification System score ≥ 3) and preparation-related factors (drinking-to-stool interval ≥ 3 h, preparation-to-colonoscopy interval ≥ 6 h, and poor rectal effluent) were found to be independently associated with inadequate BP (all P < 0.05). C-statistics was 0.81 for the preparation-related model in the training cohort (n = 604), significantly higher than three available patient-based models (0.58-0.61). Similar results were observed in the validation cohort (n = 302). Calibration curves showed close agreement in the preparation-related model (R2  = 0.315 in the training cohort and 0.279 in the validation cohort). The preparation-related model was externally validated in another 606 patients with C-index of 0.80. CONCLUSIONS: A new preparation-related model (consisting of drinking-to-stool interval ≥ 3 h, preparation-to-colonoscopy interval ≥ 6 h, and poor last rectal effluent) was developed and performed better than three available patient-related models. This easy-to-use model may be a useful decision-support tool on individualized plans in patients undergoing BP.

The Incidence and Severity of Post-ERCP Pancreatitis in Patients Receiving Standard Administration of NSAIDs: a Systematic Review and Meta-analysis.

BACKGROUND: Routine rectal administration of 100 mg of diclofenac or indomethacin was demonstrated to be an effective prevention method to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. The systematic review and meta-analysis aimed to estimate the incidence and severity of post-ERCP pancreatitis (PEP) and explore the discrepancies of PEP incidences among different subgroups. METHODS: The PubMed, Web of Science, and Ovid EMBASE databases were searched for studies published until December 2020. Only randomized controlled trials (RCTs) reported rectal administration of 100 mg or higher doses of diclofenac or indomethacin, with PEP as the primary outcomes were eligible for inclusion. The overall and severity of PEP were estimated. Subgroup analysis was performed based on geographic regions, risk level, study beginning time, type of NSAIDs, administration time, and sample size. RESULTS: There were 26 randomized controlled trials (RCTs) with 7954 patients in 31 NSAIDs arms. The pooled incidences were 7.2% for overall PEP (95% confidence interval (CI) 5.9-8.5%), 5.0% for mild PEP (95% CI, 4.0-6.0%), and 1.5% for moderate and severe PEP (0.8-2.3%). PEP rate were higher in patients receiving rectal indomethacin than that of patients receiving rectal diclofenac (7.8% (95% CI, 6.4-9.3%) vs 3.8% (95% CI, 2.2-5.3%), p = 0.009). The PEP rates of high-risk patients and average-risk patients were 8.9% (95% CI, 5.6-12.2%) and 6.4% (95% CI, 5.1-7.6%), respectively (p = 0.160). CONCLUSIONS: The incidence of PEP was higher in patients receiving 100 mg rectal indomethacin than patients receiving 100 mg diclofenac. The effect of 100 mg diclofenac versus indomethacin on preventing PEP requires further study.

Functional dyspepsia symptom diary is correlated with other questionnaires and associated with severity in patients with functional dyspepsia: a multicenter, prospective observational study.

BACKGROUND AND AIM: Functional dyspepsia symptom diary (FDSD) is a newly designed questionnaire of functional dyspepsia (FD). The relationships between FDSD and other FD-related questionnaires and patient-reported severity remain unclear. This study aims to investigate the correlations between FDSD and other questionnaires and to determine the relationships between FDSD and FD severity. METHODS: Consecutive outpatients with FD were prospectively enrolled in four tertiary hospitals. All patients were evaluated by six FD-related questionnaires, including FDSD, Dyspepsia Symptom Severity Index (DSSI), Gastrointestinal Symptom Rating Scale, Short-Form Nepean Dyspepsia Index, and Hamilton Depression and Anxiety Scale (HAMD and HAMA). The severity of FD was also graded as mild, moderate, and severe by patients themselves. Correlations between different scores were assessed by Spearman correlation coefficient (ρ), and risk factors for patient-reported severity were identified. RESULTS: For 512 enrolled FD patients, the overall median FDSD score was 19 (2-42). FDSD was well correlated with DSSI (ρ = 0.64) and fairly correlated with the other four scores (ρ = 0.32-0.55) (all P < 0.001). Mild, moderate, and severe FD were reported by 18.5%, 55.9%, and 25.6% of patients, respectively. There were seven factors associated with the severe FD, including education level, duration, and subtypes of FD, prior treatment, FDSD, HAMD, and HAMA scores (all P < 0.10). FDSD ≥ 20 (odds ratio [OR] 3.3, 95% confidence interval [CI]: 2.0-5.2, P < 0.001) and HAMD ≥ 13 (OR 2.9, 95% CI: 1.8-4.6, P < 0.001) were independently associated with patient-reported severe FD. CONCLUSIONS: This study firstly revealed that the newly developed FDSD correlated with other FD-related questionnaires. FDSD ≥ 20 and HAMD ≥ 13 were independently associated with severe FD reported by patients (clinicaltrials.gov number: NCT04953975).

Perioperative Complications of Transvenous Embolization of Ruptured Intracranial Arteriovenous Malformations.

Purpose: To investigate the perioperative complications of transvenous embolization of ruptured intracranial arteriovenous malformations. Materials and Methods: A total of 27 patients with ruptured intracranial arteriovenous malformations underwent transvenous embolization were enrolled from November 2016 to May 2020 in our prospective database. Perioperative complications and angiographic characteristics were analyzed retrospectively. Results: Complete disappearance of the nidus occured in 22 (88%) of 25 patients with technically feasible AVMs immediately after embolization. Two cases were partially treated by transarterial embolization due to the failure of microcatheter placement into the draining vein. Seven (25.9%, 7/27) patients had perioperative complications, including three cases of intraoperative hemorrhage, three cases of postoperative hemorrhage and one case of ischemic infarction. No significant differences in complication rates between patients with nidus ≥3 cm and <3 cm (P = 0.659), eloquent area and non-eloquent (P = 0.137), deep location and superficial (P = 0.637), deep venous drainage and cortical vein (P = 1.0), the number of venous drainage (P = 0.49), the angle of draining vein entering venous sinus <90° and ≥90° (P = 1.0), aneurysms (P = 0.058) and the time between hemorrhage and TVE (P = 1.0) were found. Three of these patients received ventriculostomy, two of which received lumbar drainage treatments at the same time, and four patients just received conservative management. Good outcomes (mRS ≤ 2) at the 1-month evaluation were achieved in 5 of the patients who had complications, but poor outcome (mRS = 5) at the 1-month evaluation was in 1 patient, and 1 lethal complication occurred. Conclusion: The most common complication of AVMs with transvenous endovascular embolization is cerebral hemorrhage. The prevention of complications may improve the efficacy of AVM embolization, but the current quality of evidence is low and limited in guiding policy development and improving the TVE for AVMs. It is, therefore, necessary to develop clinical research programs in this field.

Microbial Characteristics of Common Tongue Coatings in Patients with Precancerous Lesions of the Upper Gastrointestinal Tract.

The tongue coating (TC) microbiota, a crucial component of the tongue coating, illustrates a huge microbial percentage of the body that mostly includes actinobacteria, bacteroides, firmicutes, and fusobacteria. The TC microbiota is closely related to the development of upper gastrointestinal malignancies, such as oral, gastric, and esophageal cancer. Nonetheless, the microbiological characteristics of common TCs in individuals with precancerous lesions of the upper gastrointestinal tract are still unclear. Herein, we designed a case-control study, recruiting 153 PLUGT patients with four different types of TCs, including 47 white-thin, 19 white-thick, 47 yellow-thin, and 40 yellow-thick, as well as 47 volunteers as controls. To analyze microbial characteristics, 16S rRNA microbiome approaches were used. An enzyme-linked immunosorbent assay (ELISA) was employed to assess serum IL-17A and total bile acid (TBA). According to the obtained results, Leptotrichia was found to be a promising biomarker for thin as well as thick yellow coatings. In comparison to the control TC microbiota, 39 different genera developed commensal networks in common TCs. Lachnoanaerobaculum and pseudonocardia were the most striking core bacteria. Lachnoanaerobaculum positively correlated with Leptotrichia in W-thin and Y-thick coatings, with actinomyces and methylobacterium in Y-thin coatings, with Campylobacter in Y-thick coatings, and with Bradyrhizobium in W-thick and Y-thick coatings. Serum IL-17A levels were greater in cases with W-thin coating than in controls, and serum IL-17A was positively linked with Parvimonas in patients with W-thick or Y-thin coating. In Y-thin coating, the oral dominating bacteria Streptococcus was negatively linked with serum TBA. Taken together, the promoted bacteria were found to be synergistically proliferative in the TCs of PLUGT patients. The diverse TCs had distinct bacterial commensal networks, whereas the common TCs were linked by specific bacteria to serum IL-17A and TBA.

Yishen Qingli Heluo Granule in the Treatment of Chronic Kidney Disease: Network Pharmacology Analysis and Experimental Validation.

Background: Chronic kidney disease (CKD) is considered a global public health problem with high morbidity and mortality. Yishen Qingli Heluo granule (YQHG) is representative traditional Chinese medicine (TCM) remedy for clinical treatment of CKD. This study aims to explore the mechanism of YQHG on CKD through network pharmacology and experimental validation. Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and wide-scale literature mining were applied to screen active compounds of YQHG. Multiple bioinformatic tools and online databases were applied by us to obtain relevant targets of YQHG and CKD. The intersection targets between YQHG and CKD were considered as candidate targets. The compound-target, herb-candidate target and protein-protein interaction networks were constructed and visualized for topological analyses. GO and KEGG enrichment analyses were conducted to determine the biological processes and signaling pathways. Molecular docking was used to verify the reliability of network pharmacology. Finally, pharmacological evaluation was performed to explore the mechanism of YQHG against CKD on a 5/6 nephrectomy model. Results: Seventy-nine candidate targets, ten core biological processes and one key signaling pathway (p53) were screened. PTGS2 was identified as a key target based on H-CT network. The molecular docking showed that Quercetin, Kaempferol, Luteolin were three key compounds with the best binding activity. In addition, IL6 and Quercetin could form a stable complex with high binding affinity (-7.29 kcal/mol). In vivo experiment revealed that YQHG improved kidney function and fibrosis in 5/6 nephrectomized rats. Moreover, the decreased expression of PTGS2, IL6, and the increased expression of p53 were observed in kidney tissue. Notably, the gut microbiota of rats treated with YQHG was reshaped, which was characterized by a reduced ratio of Firmicutes/Bacteroidota. Conclusion: Our results predicted and verified the potential targets of YQHG on CKD from a holistic perspective, and provided valuable direction for the further research of YQHG.

Influence of Oral Intaking Habit on Tongue Coating Microbiota in Patients with Esophageal Precancerous Lesions.

Background: Esophageal cancer (EC) is a common digestive tract tumor in China, and oral intaking habit has a great influence on the development of EC. The present study explored the correlation between oral intaking habit and tongue coating (TC) microbiota in patients with esophageal precancerous lesions (EPL) to provide a reasonable interpretation of the influence of oral intaking habit on microbial alterations in the EPL. Methods: A case-control study was designed with 123 EPL patients and 176 volunteers with mild esophagitis, and they were well matched using sex, age, and body mass index. The TC microbiota was profiled using high-throughput sequencing of the V3-V4 region of the 16S rRNA gene, and the serum levels of total bile acid (TBA) and interleukin-17α (IL-17α) were measured using enzyme-linked immunosorbent assay. Alpha diversity, community structure, and linear discriminant analysis were conducted, and Spearman correlation analysis was used to build the symbiotic network. Results: No significant differences were observed in the diversity and richness of the TC microbiota between the cases and controls (P > 0.05). TC Peptostreptococcus and Capnocytophaga were enriched in EPL patients. Stratified analysis showed that TC microbial composition was affected by both EPL and oral intaking habit; for example, Atopobium and Actinomyces were positively related to oral intaking habit scores in both the cases and controls, while Simonsiella was negatively correlated with oral intaking habit status in cases but positively correlated with oral intaking habit status in controls. Although serum TBA and IL-17α were not associated with EPL (P > 0.05), the daily-drinking cases had a higher level of serum TBA than the nondrinking cases (P < 0.05), and Helicobacter pylori (Hp) negative controls had a higher level of serum TBA than the Hp-positive controls (P < 0.05). The symbiotic networks were comprised of 71 significant correlations in the controls and 52 significant correlations in the cases. Conclusions: The development of EPL changed the TC microbiota and decreased the symbiotic complexity of the TC bacteria, which were also influenced by the cancer-related oral intaking habit. Bile acid may be a key factor mediating changes in TC microbiota.

Endoscopic Papillary Large Balloon Dilation Reduces Further Recurrence in Patients With Recurrent Common Bile Duct Stones: A Randomized Controlled Trial.

INTRODUCTION: Up to 60% of patients with common bile duct stone (CBDS) recurrence suffer from further recurrence after endoscopic retrograde cholangiopancreatography (ERCP). There are no effective methods to prevent recurrence in most patients. In this study, we aimed to assess the short-term and long-term efficacies of endoscopic papillary large balloon dilation (EPLBD) for the management of recurrent CBDS in a randomized controlled trial. METHODS: Consecutive patients with recurrent CBDS were eligible and randomly assigned in a 1:1 ratio to the EPLBD group or the control group. The primary outcome was the CBDS recurrence rate within 2 years after ERCP. The analysis followed the intention-to-treat principle. RESULTS: From 2014 to 2021, 180 patients with recurrent CBDS were included, with 90 in each group. All patients underwent complete CBDS clearance by 1 or several sessions of ERCP. The rate of complete clearance in 1 session was significantly higher with EPLBD treatment (95.6% vs 85.6%, P = 0.017). During the follow-up, the CBDS recurrence rate within 2 years was significantly lower in the EPLBD group than in the control group (21.1% [19/90] vs 36.7% [33/90], relative risk 0.58, 95% confidence interval 0.36-0.93, P = 0.021). At a median follow-up of approximately 56 months, CBDS recurrence was found in 34.4% of the patients (31/90) in the EPLBD group and 51.1% (46/90) in the control group (hazard ratio 0.57, 95% confidence interval 0.36-0.89, P = 0.012). Multiple recurrences (≥2) were also decreased in the EPLBD group (4.4% vs 18.9%, P = 0.020). DISCUSSION: During the long-term follow-up, nearly half of the patients with recurrent CBDS experienced stone recurrence after traditional ERCP. Our study was the first to show that EPLBD effectively reduced the recurrence of CBDS.

Thin Layer-Protected Gold Nanoparticles for Targeted Multimodal Imaging with Photoacoustic and CT.

The large size of nanoparticles prevents rapid extravasation from blood vessels and diffusion into tumors. Multimodal imaging uses the physical properties of one modality to validate the results of another. We aim to demonstrate the use of a targeted thin layer-protected ultra-small gold nanoparticles (Au-NPs) to detect cancer in vivo using multimodal imaging with photoacoustic and computed tomography (CT). The thin layer was produced using a mixed thiol-containing short ligands, including MUA, CVVVT-ol, and HS-(CH2)11-PEG4-OH. The gold nanoparticle was labeled with a heterobivalent (HB) peptide ligand that targets overexpression of epidermal growth factor receptors (EGFR) and ErbB2, hereafter HB-Au-NPs. A human xenograft model of esophageal cancer was used for imaging. HB-Au-NPs show spherical morphology, a core diameter of 4.47 ± 0.8 nm on transmission electron microscopy, and a hydrodynamic diameter of 6.41 ± 0.73 nm on dynamic light scattering. Uptake of HB-Au-NPs was observed only in cancer cells that overexpressed EGFR and ErbB2 using photoacoustic microscopy. Photoacoustic images of tumors in vivo showed peak HB-Au-NPs uptake at 8 h post-injection with systemic clearance by ~48 h. Whole-body images using CT validated specific tumor uptake of HB-Au-NPs in vivo. HB-Au-NPs showed good stability and biocompatibility with fast clearance and contrast-enhancing capability for both photoacoustic and CT imaging. A targeted thin layer-protected gold nanoprobe represents a new platform for molecular imaging and shows promise for early detection and staging of cancer.