Evaluating the causal association between bronchiectasis and different types of inflammatory bowel disease: a two-sample Mendelian randomization study.

Background and objectives: Previous observational studies have established a connection between bronchiectasis and inflammatory bowel disease (IBD), but none of these studies have provided a clear explanation for the underlying cause of this relationship. The present study thus implemented Mendelian randomization (MR) design to explore possible bidirectional relationships between IBD and bronchiectasis risk, with an additional focus on Crohn's disease (CD) and ulcerative colitis (UC) as IBD subtypes. Materials and methods: A large genome-wide association study (GWAS)-derived data pool was leveraged to examine the relationships between bronchiectasis and IBD, CD, and UC. Two-sample MR analyses were performed with an inverse variance weighted (IVW) approach supplemented with the MR-Egger and weighted median methods. Sensitivity analyses were used to further assess the reliability of the main MR study findings. The possibility of reverse causation was also evaluated using a reverse MR approach. Results: The IVW MR analytical approach revealed that IBD (p = 0.074), UC (p = 0.094), and CD (p = 0.644) had no significant impact on the incidence of bronchiectasis, with the converse also being true (p = 0.471, p = 0.700, and p = 0.099, respectively). Conclusion: This MR analysis demonstrated that the higher occurrence of bronchiectasis in patients with IBD is not caused by genetic predisposition.

The perilous consequences of bowel preparation: a case study with literature review of Boerhaave syndrome.

Colonoscopy is widely acknowledged as a prevalent and efficacious approach for the diagnosis and treatment of gastrointestinal disorders. In order to guarantee an effective colonoscopy, it is imperative for patients to undergo an optimal bowel preparation regimen. This entails the consumption of a substantial volume of a non-absorbable solution to comprehensively purge the colon of any fecal residue. Nevertheless, it is noteworthy to acknowledge that the bowel preparation procedure may occasionally elicit adverse symptoms such as nausea and vomiting. In exceptional instances, the occurrence of excessive vomiting may lead to the rupture of the distal esophagus, a grave medical condition referred to as Boerhaave syndrome (BS). Timely identification and efficient intervention are imperative for the management of this infrequent yet potentially perilous ailment. This investigation presents a case study of a patient who developed BS subsequent to the ingestion of mannitol during bowel preparation. Furthermore, an exhaustive examination of extant case reports and pertinent literature on esophageal perforation linked to colonoscopy has been conducted. This analysis provides valuable insights into the prevention, reduction, and treatment of such serious complications.

Clinical significance of postoperative folate receptor-positive circulating tumor cells (FR + CTCs) for long-term prognosis in patients with invasive adenocarcinoma (IAC) of the lung.

BACKGROUND: The aim of the study was to evaluate the prognostic value of postoperative folate receptor-positive circulating tumor cell (FR + CTC) detection in patients with stage I-III invasive adenocarcinoma (IAC) treated with surgery. METHODS: Patients with lung adenocarcinoma (LUAD) who underwent surgical resection in Peking University Cancer Hospital and received postoperative FR + CTC analysis from July 2016 to January 2021 were retrospectively collected. Comparisons between or among groups were made using the Kruskal-Wallis or Mann-Whitney U tests. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazard regression analyses were performed to explore the factors predicting recurrence and survival. RESULTS: There were significant differences between the high and low groups in terms of age (p = 0.002), postoperative CA199 (p = 0.038), and postoperative SCC (p = 0.024). There were no significant differences in the other indicators (all p>0.05). N stage 1, N stage 2, and neoadjuvant therapy (NAT) were independent risk factors for disease recurrence and death; pleural invasion (PI), and nerve invasion were independent risk factors for death. The Kaplan-Meier curve showed a notable trend for a worse disease-free survival (DFS) or overall survival (OS) for patients with high levels of FR + CTCs in our study, but none of these were statistically significant. CONCLUSION: The detection of FR + CTCs postoperatively was an independent predictor of recurrence in patients treated for stage I-III IAC. Standardized detection methods and optimal time points for assessment should be established in future studies.

SingleQ: a comprehensive database of single-cell expression quantitative trait loci (sc-eQTLs) cross human tissues.

Mapping of expression quantitative trait loci (eQTLs) and other molecular QTLs can help characterize the modes of action of disease-associated genetic variants. However, current eQTL databases present data from bulk RNA-seq approaches, which cannot shed light on the cell type- and environment-specific regulation of disease-associated genetic variants. Here, we introduce our Single-cell eQTL Interactive Database which collects single-cell eQTL (sc-eQTL) datasets and provides online visualization of sc-eQTLs across different cell types in a user-friendly manner. Although sc-eQTL mapping is still in its early stage, our database curates the most comprehensive summary statistics of sc-eQTLs published to date. sc-eQTL studies have revolutionized our understanding of gene regulation in specific cellular contexts, and we anticipate that our database will further accelerate the research of functional genomics. Database URL: http://www.sqraolab.com/scqtl.

Nomogram for predicting pathological response to neoadjuvant treatment in patients with locally advanced gastric cancer: Data from a phase III clinical trial.

PURPOSE: This study aimed to establish a nomogram using routinely available clinicopathological parameters to predict the pathological response in patients with locally advanced gastric cancer (LAGC) undergoing neoadjuvant treatment. MATERIALS AND METHODS: We conducted this study based on the ongoing Neo-CRAG trial, a prospective study focused on preoperative treatment in patients with LAGC. A total of 221 patients who underwent surgery following neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) at Sun Yat-sen University Cancer Center between June 2013 and July 2022 were included in the analysis. We defined complete or near-complete pathological regression and ypN0 as good response (GR), and determined the prognostic value of GR by Kaplan-Meier survival analysis. Eventually, a nomogram for predicting GR was developed based on statistically identified predictors through multivariate logistic regression analysis and internally validated by the bootstrap method. RESULTS: GR was confirmed in 54 patients (54/221, 24.4%). Patients who achieved GR had a longer progression-free survival and overall survival. Then, five independent factors, including pretreatment tumor differentiation, clinical T stage, monocyte count, CA724 level, and the use of nCRT, were identified. Based on these predictors, the nomogram was established with an area under the curve (AUC) of 0.777 (95% CI, 0.705-0.850) and a bias-corrected AUC of 0.752. CONCLUSION: A good pathological response after neoadjuvant treatment was associated with an improved prognosis in LAGC patients. The nomogram we established exhibits a high predictive capability for GR, offering potential value in devising personalized and precise treatment strategies for LAGC patients.

Insensitivity of oncogenic EGFR R776L mutation to EGFR inhibitors in lung cancer.

Non-small cell lung cancers (NSCLC) account for 85 % of total lung cancers. Mutation in EGFRdrives the progress of NSCLSs with high mortality rate. Besides the common mutations in EGFR, which together comprise of 85 % of all EGFR mutations and respond to the targeted therapy of EGFR tyrosine kinase inhibitors (TKIs), many other low-frequency mutations of EGFR are existed in patients. The oncogenic roles and sensitivity of these mutations to EGFR TKIs are not fully understood yet. Here we described two cases of lung adenocarcinoma patients harboring EGFR R776L missense mutation, showed PD and SD after treatment with third-generation EGFR inhibitor, Almonertinib. Chemotherapy afterward showed PR effect in one patient with PSF of 10 months. We also explored the oncogenic feature of single R776L mutation by Ba/F3 isogenic cells and found that, EGFR R776L mutation activates EGFR-related survival signaling pathway in Ba/F3 cells, and they are insensitive to gefitinib, afatinib, and Almonertinib, which consistent with our clinical observation.

Oncological risk of proximal gastrectomy for proximal advanced gastric cancer after neoadjuvant chemotherapy.

PURPOSE: This study assesses the metastasis rate of the key distal lymph nodes (KDLN) that are not routinely dissected in proximal gastrectomy, aiming to explore the oncological safety of proximal gastrectomy for upper gastric cancer who underwent neoadjuvant chemotherapy. METHODS: We analyzed a cohort of 150 patients with proximal locally advanced gastric cancer (cT3/4 before chemotherapy) from two high-volume cancer centers in China who received preoperative neoadjuvant chemotherapy (NAC) and total gastrectomy with lymph node dissection. Metastasis rate of the KDLN (No.5/6/12a) and the risk factors were analyzed. RESULTS: Key distal lymph node metastasis was detected in 10% (15/150) of patients, with a metastasis rate of 6% (9/150) in No. 5 lymph nodes, 6.7% (10/150) in No. 6 lymph nodes, and 2.7% (2/75) in No. 12a lymph nodes. The therapeutic value index of KDLN as one entity is 5.8. Tumor length showed no correlation with KDLN metastasis, while tumor regression grade (TRG) emerged as an independent risk factor (OR: 1.47; p-value: 0.04). Of those with TRG3 (no response to NAC), 80% (12/15) was found with KDLN metastasis. CONCLUSION: For cT3/4 proximal locally advanced gastric cancer patients, the risk of KDLN metastasis remains notably high even after NAC. Therefore, proximal gastrectomy is not recommended; instead, total gastrectomy with thorough distal lymphadenectomy is the preferred surgical approach.

Functional characterization of D-type cyclins involved in cell division in rice.

BACKGROUND: D-type cyclins (CYCD) regulate the cell cycle G1/S transition and are thus closely involved in cell cycle progression. However, little is known about their functions in rice. RESULTS: We identified 14 CYCD genes in the rice genome and confirmed the presence of characteristic cyclin domains in each. The expression of the OsCYCD genes in different tissues was investigated. Most OsCYCD genes were expressed at least in one of the analyzed tissues, with varying degrees of expression. Ten OsCYCD proteins could interact with both retinoblastoma-related protein (RBR) and A-type cyclin-dependent kinases (CDKA) forming holistic complexes, while OsCYCD3;1, OsCYCD6;1, and OsCYCD7;1 bound only one component, and OsCYCD4;2 bound to neither protein. Interestingly, all OsCYCD genes except OsCYCD7;1, were able to induce tobacco pavement cells to re-enter mitosis with different efficiencies. Transgenic rice plants overexpressing OsCYCD2;2, OsCYCD6;1, and OsCYCD7;1 (which induced cell division in tobacco with high-, low-, and zero-efficiency, respectively) were created. Higher levels of cell division were observed in both the stomatal lineage and epidermal cells of the OsCYCD2;2- and OsCYCD6;1-overexpressing plants, with lower levels seen in OsCYCD7;1-overexpressing plants. CONCLUSIONS: The distinct expression patterns and varying effects on the cell cycle suggest different functions for the various OsCYCD proteins. Our findings will enhance understanding of the CYCD family in rice and provide a preliminary foundation for the future functional verification of these genes.

Coupling pretreatment of ultraviolet/ferrate (UV/Fe(vi)) for improving the ultrafiltration of natural surface water.

Ultrafiltration (UF) is a high-potential technology for purifying natural surface water; however, the problem of membrane fouling has limited its widespread application. Herein, ultraviolet (UV)-activated ferrate (Fe(vi)) was used to purify natural surface water and improve the performance of the UF membrane. The combination of UV and Fe(vi) could generate active species (Fe(v), Fe(iv), ˙OH and O2˙-) to degrade pollutants, while the in situ produced Fe(iii) had the effect of coagulation. With the above action, pollutants were removed, and the pollution load of natural surface water was reduced. After treatment with the UV/Fe(vi) system, dissolved organic carbon was reduced by 49.38%, while UV254 was reduced by 45.00%. The removal rate was further increased to 54.88% and 51.67% after UF treatment. In addition, the fluorescent organics were reduced by 44.22%, and the molecular weight of the organics became smaller. In the stage of UF, the terminal J/J0 was increased from 0.61 to 0.92, and the membrane fouling resistance was decreased by 85.94%. The analysis of the membrane fouling mechanism indicates that the role of cake filtration was weakened among all the mechanisms. Fourier transform infrared spectroscopy showed that less pollutants were accumulated on the membrane surface, and scanning electron microscopy revealed that the membrane pore blockage was relieved. In summary, the UV/Fe(vi) co-treatment process proposed in this study can significantly improve the purification efficiency of the UF systems in natural surface water treatment.

Long-term oncological outcomes of robotic versus laparoscopic gastrectomy for gastric cancer: multicentre cohort study.

BACKGROUND: The aim of this multicentre cohort study was to compare the long-term oncological outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for patients with gastric cancer. METHODS: Patients with gastric cancer who underwent radical gastrectomy by robotic or laparoscopic approaches from 1 March 2010 to 31 December 2018 at 10 high-volume centres in China were selected from institutional databases. Patients receiving RG were matched 1 : 1 by propensity score with patients undergoing LG. The primary outcome was 3-year disease-free survival. Secondary outcomes were overall survival and disease recurrence. RESULTS: Some 2055 patients who underwent RG and 4309 patients who had LG were included. The propensity score-matched cohort comprised 2026 RGs and 2026 LGs. Median follow-up was 41 (i.q.r. 39-58) months for the RG group and 39 (38-56) months for the LG group. The 3-year disease-free survival rates were 80.8% in the RG group and 79.5% in the LG group (log rank P = 0.240; HR 0.92, 95% c.i. 0.80 to 1.06; P = 0.242). Three-year OS rates were 83.9 and 81.8% respectively (log rank P = 0.068; HR 0.87, 0.75 to 1.01; P = 0.068) and the cumulative incidence of recurrence over 3 years was 19.3% versus 20.8% (HR 0.95, 0.88 to 1.03; P = 0.219), with no difference between groups. CONCLUSION: RG and LG in patients with gastric cancer are associated with comparable disease-free and overall survival.

Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial.

Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 .

Chromosome-level assembly and analysis of Camelina neglecta: a novel diploid model for Camelina biotechnology research.

Camelina neglecta is a new diploid Brassicaceae species, which has great research value because of its close relationship with the hexaploid oilseed crop Camelina sativa. Here, we report a chromosome-level assembly of C. neglecta with a total length of 210 Mb. By adopting PacBio sequencing and Hi-C technology, the C. neglecta genome was assembled into 6 chromosomes with scaffold N50 of 29.62 Mb. C. neglecta has undergone the whole-genome triplication (γ) shared among eudicots and two whole-genome duplications (α and ß) shared by crucifers, but it has not undergone a specific whole-genome duplication event. By synteny analysis between C. neglecta and C. sativa, we successfully used the method of calculating Ks to distinguish the three subgenomes of C. sativa and determined that C. neglecta was closest to the first subgenome (SG1) of C. sativa. Further, transcriptomic analysis revealed the key genes associated with seed oil biosynthesis and its transcriptional regulation, including SAD, FAD2, FAD3, FAE1, ABI3, WRI1 and FUS3 displaying high expression levels in C. neglecta seeds. The high representability of C. neglecta as a model species for Camelina-based biotechnology research has been demonstrated for the first time. In particular, floral Agrobacterium tumefaciens infiltration-based transformation of C. neglecta, leading to overexpression of CvLPAT2, CpDGAT1 and CvFatB1 transgenes, was demonstrated for medium-chain fatty acid accumulation in C. neglecta seed oil. This study provides an important genomic resource and establishes C. neglecta as a new model for oilseed biotechnology research.

Two haplotype-resolved genome assemblies for AAB allotriploid bananas provide insights into banana subgenome asymmetric evolution and Fusarium wilt control.

Bananas (Musa spp.) are one of the world's most important fruit crops and play a vital role in food security for many developing countries. Most banana cultivars are triploids derived from inter- and intraspecific hybridizations between the wild diploid ancestor species Musa acuminate (AA) and M. balbisiana (BB). We report two haplotype-resolved genome assemblies of the representative AAB-cultivated types, Plantain and Silk, and precisely characterize ancestral contributions by examining ancestry mosaics across the genome. Widespread asymmetric evolution is observed in their subgenomes, which can be linked to frequent homologous exchange events. We reveal the genetic makeup of triploid banana cultivars and verify that subgenome B is a rich source of disease resistance genes. Only 58.5% and 59.4% of Plantain and Silk genes, respectively, are present in all three haplotypes, with >50% of genes being differentially expressed alleles in different subgenomes. We observed that the number of upregulated genes in Plantain is significantly higher than that in Silk at one-week post-inoculation with Fusarium wilt tropical race 4 (Foc TR4), which confirms that Plantain can initiate defense responses faster than Silk. Additionally, we compared genomic and transcriptomic differences among the genes related to carotenoid synthesis and starch metabolism between Plantain and Silk. Our study provides resources for better understanding the genomic architecture of cultivated bananas and has important implications for Musa genetics and breeding.

Efficacy Analysis of Drug-Coated Balloons in the Treatment of Ultra-Long Segment Lesions of Femoral Popliteal Artery.

BACKGROUND: To evaluate the midterm clinical efficacy of paclitaxel drug-coated balloons (DCBs) in the treatment of femoral artery TransAtlantic Inter-Society Consensus (TASC) grades C/D lesions. METHODS: The clinical data of 73 cases with TASC grades C/D lesions of femoral artery treated with paclitaxel DCBs at the Department of Vascular Surgery, the First Hospital of Fujian Medical University from August 2016 to January 2020 were retrospectively analyzed. The primary endpoint was the primary patency rate. The secondary endpoints were freedom from reintervention, Rutherford classification, ankle-brachial index (ABI), amputation events, and all-cause death. RESULTS: A total of 73 cases of limb lesions received endoluminal treatment. The mean age of the patients including 49 males and 24 females was (72.66 ± 11.1) years, with an initial Rutherford classification of 2-5 and an ABI of 0.4 ± 0.1. The mean Rutherford classification was 3.70 ± 0.95. The mean lesion length was (25.75 ± 9.67) cm, including 61.64% chronic occlusive lesions and 27.39% stenotic lesions, the remaining 10.97% were mixed lesions, containing multiple segments of stenosis and chronic total occlusion lesions. 43.8% of the lesions were associated with severe calcification. Stent implantation rate was 8%. Overall mortality at follow-up was 4% at 1 year and 8% at 2 years, and no amputations seen. The ABI was 0.83 ± 0.07 at 1-year follow-up and 0.78 ± 0.05 at 2-year follow-up. The Kaplan-Meier survival curve predicted the 1-year phase I patency rate was 75.3% ± 5% and the 2-year patency rate was 63.3% ± 5.7%. Freedom from target lesion revascularization was 78.4 ± 4.9% at 1 year and 69.2% ± 3.6% at 2 years. Logistic regression analysis showed that diabetes mellitus, severe calcification, chronic renal insufficiency, and restenosis were the significant factors affecting the patency of target lesions. CONCLUSIONS: Paclitaxel DCBs in the treatment of femoral artery with TASC grades C/D lesions can achieve relatively satisfactory midterm clinical safety and efficacy results, provided there is an acceptable result on completion angiogram.

HSP90ß regulates EAAT2 expression and participates in ischemia­reperfusion injury in rats.

Cerebrovascular diseases (CVDs) have become a global public health problem and ischemia­reperfusion injury, the major cause of neurological impairment exacerbation, is closely related to excitotoxicity. The present study aimed to investigate the effects of changes in heat shock protein (HSP)90ß expression and verify whether HSP90ß regulates EAAT2 expression in a cerebral ischemia­reperfusion injury model. Healthy adult Sprague­Dawley (SD) male rats were used to establish a control group, sham­operated group, middle cerebral artery occlusion (MCAO) group, empty virus group and lentivirus group. A model of cerebral ischemia­reperfusion was established using the MCAO method. Lentivirus construction and injection were used to interfere with the expression of HSP90ß. The modified neurological severity score was used to assess neurological deficits. Triphenyltetrazolium chloride staining was used to detect infarct areas. Immunofluorescence was used to detect HSP90ß expression localization and the expression levels of HSP90ß and EAAT2 were determined using western blotting and reverse transcription­quantitative PCR. An MCAO model was successfully established and it was found that HSP90ß, but not HSP90α, was upregulated after MCAO. HSP90ß expression coincided with astrocyte markers in the ischemic penumbra area, while no expression was observed in microglia. Inhibition of HSP90ß expression improved neurological deficits and alleviated brain injury by increasing EAAT2 expression. These results suggested that HSP90ß is involved in the process of cerebral ischemia­reperfusion injury in rats and that inhibition of HSP90ß expression increases EAAT2 levels, conferring a neuroprotective effect in MCAO model rats.

Catalytic degradation of chlorinated volatile organic compounds (CVOCs) over Ce-Mn-Ti composite oxide catalysts.

Developing industrially moldable catalysts with harmonized redox performance and acidity is of great significance for the efficient disposal of chlorinated volatile organic compounds (CVOCs) in actual exhaust gasses. Here, commercial TiO2, typically used for molding catalysts, was chosen as the carrier to fabricate a series of Ce0.02Mn0-0.24TiOx materials with different Mn doping ratios and employed for chlorobenzene (CB) destruction. The introduction of Mn remarkedly facilitated the synergistic effect of each element via the electron transfer processes: Ce3++Mn4+/3+↔Ce4++Mn3+/2+ and Mn4+/3++Ti4+↔Mn3+/2++Ti3+. These synergistic interactions in Ce0.02Mn0.04-0.24TiOx, especially Ce0.02Mn0.16TiOx, significantly elevated the active oxygen species, oxygen vacancies and redox properties, endowing the superior catalytic oxidation of CB. When the Mn doping amount increased to 0.24, a separate Mn3O4 phase appeared, which in turn might weaken the synergistic effect. Furthermore, the acidity of Ce0.02Mn0.04-0.24TiOx was decreased with the Mn doping, regulating the balance of redox property and acidity. Notably, Ce0.02Mn0.16TiOx featured relatively abundant B-acid sites. Its coordinating redox ability and moderate acidity promoted the deep oxidation of CB and RCOOH- intermediates, as well as the rapid desorption of Cl species, thus obtaining sustainable reactivity. In comparison, CeTiOx owned the strongest acidity, however, its poor redox property was not sufficient for the timely oxidative decomposition of the easier adsorbed CB, resulting in its rapid deactivation. This finding provides a promising strategy for the construction of efficient commercial molding catalysts to decompose the industrial-scale CVOCs.