ABSTRACT
BACKGROUND: The incidence and mortality of colorectal cancer (CRC) in China are increasing in recent years. The clarified pathogenesis and detectable precancerous lesions of CRC make it possible to prevent, screen, and diagnose CRC at an early stage. With the development of endoscopic and surgical techniques, the choice of treatment for early CRC is also worth further discussion, and accordingly, a standard follow-up program after treatment needs to be established. METHODS: This clinical practice guideline (CPG) was developed following the recommended process of the World Health Organization, adopting Grading of Recommendations Assessment, Development and Evaluation (GRADE) in assessing evidence quality, and using the Evidence to Decision framework to formulate clinical recommendations, thereby minimizing bias and increasing transparency of the CPG development process. We used the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement and Appraisal of Guidelines for Research and Evaluation II (AGREE II) as reporting and conduct guides to ensure the guideline's completeness and transparency. RESULTS: This CPG comprises 46 recommendations concerning prevention, screening, diagnosis, treatment, and surveillance of CRC. In these recommendations, we have indicated protective and risk factors for CRC and made recommendations for chemoprevention. We proposed a suitable screening program for CRC based on the Chinese context. We also provided normative statements for the diagnosis, treatment, and surveillance of CRC based on existing clinical evidence and guidelines. CONCLUSIONS: The 46 recommendations in this CPG are formed with consideration for stakeholders' values and preferences, feasibility, and acceptability. Recommendations are generalizable to resource-limited settings with similar CRC epidemiology pattern as China.
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Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature infants characterized by alveolar dysplasia, vascular simplification and dysmorphic vascular development. Supplemental oxygen and mechanical ventilation commonly used as life-saving measures in premature infants may cause BPD. microRNAs (miRNAs), a class of small, non-coding RNAs, regulate target gene expression mainly through post-transcriptional repression. miRNAs play important roles in modulating oxidative stress, proliferation, apoptosis, senescence, inflammatory responses, and angiogenesis. These cellular processes play pivotal roles in the pathogenesis of BPD. Accumulating evidence demonstrates that miRNAs are dysregulated in the lung of premature infants with BPD, and in animal models of this disease, suggesting contributing roles of dysregulated miRNAs in the development of BPD. Therefore, miRNAs are considered promising biomarker candidates and therapeutic agents for this disease. In this review, we discuss how dysregulated miRNAs and their modulation alter cellular processes involved in BPD. We then focus on therapeutic approaches targeting miRNAs for BPD. This review provides an overview of miRNAs as biomarkers, and highlights potential pathogenic roles, and therapeutic strategies for BPD using miRNAs.
Subject(s)
Biomarkers , Bronchopulmonary Dysplasia , MicroRNAs , Bronchopulmonary Dysplasia/genetics , Bronchopulmonary Dysplasia/metabolism , Bronchopulmonary Dysplasia/therapy , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Biomarkers/metabolism , Infant, Newborn , Animals , Infant, PrematureABSTRACT
BACKGROUND: Accurate evaluation of the response to preoperative treatment enables the provision of a more appropriate personalized therapeutic schedule for locally advanced rectal cancer (LARC), which remains an enormous challenge, especially neoadjuvant immunotherapy plus chemoradiotherapy (nICRT). METHODS: This prospective, multicenter cohort study enrolled patients with LARC from 6 centers who received nICRT. The dynamic variation in the gut microbiome during nICRT was evaluated. A species-level gut microbiome prediction (SPEED) model was developed and validated to predict the pathological complete response (pCR) to nICRT. FINDINGS: A total of 50 patients were enrolled, 75 fecal samples were collected from 33 patients at different time points, and the pCR rate reached 42.4% (14/33). Lactobacillus and Eubacterium were observed to increase after nICRT. Additionally, significant differences in the gut microbiome were observed between responders and non-responders at baseline. Significantly higher abundances of Lachnospiraceaebacterium and Blautiawexlerae were found in responders, while Bacteroides, Prevotella, and Porphyromonas were found in non-responders. The SPEED model showcased a superior predictive performance with areas under the curve of 98.80% (95% confidence interval [CI]: 95.67%-100%) in the training cohort and 77.78% (95% CI: 65.42%-88.29%) in the validation cohort. CONCLUSIONS: Programmed death 1 (PD-1) blockade plus concurrent long-course CRT showed a favorable pCR rate and is well tolerated in microsatellite-stable (MSS)/mismatch repair-proficient (pMMR) patients with LARC. The SPEED model can be used to predict the pCR to nICRT based on the baseline gut microbiome with high robustness and accuracy, thereby assisting clinical physicians in providing individualized management for patients with LARC. FUNDING: This research was funded by the China National Natural Science Foundation (82202884).
ABSTRACT
MicroRNAs (miRNAs) have started to play an important role in pest control, and novel miRNA-based transgenic insect-resistant plants are now emerging. However, an environmental risk assessment of these novel transgenic plants expressing insect miRNAs must be undertaken before promoting their application. Here, transgenic miR-14 rice, which has high resistance to the rice stem borer Chilo suppressalis, was used as an example for evaluation in this study. Taking the tier 1 risk assessment method in Bacillus thuringiensis (Bt) crops as a reference, the effects of the direct exposure of a non-target parasitoid, Cotesia chilonis, to a high concentration of miRNA were evaluated. The results showed that direct feeding with miR-14 at high concentration had no significant effects on the biological parameters of Co. chilonis, whereas when miR-14 was injected into Ch. suppressalis-parasitized larvae, the development duration of Co. chilonis was significantly affected. In combination with the real conditions of the rice paddy field, it could be inferred that transgenic miR-14 rice has no significant negative effects on the important non-target parasitoid, Co. chilonis. These results will provide a foundation for the establishment of a new safety evaluation system for novel RNAi-based transgenic plants.
Subject(s)
Anastomotic Leak , Colectomy , Humans , Anastomotic Leak/etiology , Colectomy/adverse effectsABSTRACT
BACKGROUND: The CRC-VTE trial conducted in China revealed a significant occurrence of venous thromboembolism (VTE) in patients following colorectal cancer (CRC) surgery, raising concerns about implementing thromboprophylaxis measures. The present study aimed to identify and analyze inappropriate aspects of current thromboprophylaxis practices. METHODS: This study performed an analysis of the CRC-VTE trial, a prospective multicenter study that enrolled 1836 patients who underwent CRC surgery. The primary objective was to identify independent risk factors for VTE after CRC surgery using multivariate logistic regression analysis. Furthermore, among the cases in which VTE occurred, the appropriateness of thromboprophylaxis was assessed based on several factors, including pharmacologic prophylaxis, time to initiate prophylaxis, drug selection, drug dosage, and duration of pharmacologic prophylaxis. Based on the analysis of the current state of thromboprophylaxis and relevant clinical guidelines, a modified Delphi method was used to develop a clinical pathway for VTE prophylaxis after CRC surgery. RESULTS: In this analysis of 1836 patients, 205 (11.2%) were diagnosed with VTE during follow-up. The multifactorial analysis identified several independent risk factors for VTE, including age (≥70 years), female sex, varicose veins in the lower extremities, intraoperative blood transfusion, and the duration of immobilization exceeding 24 h. None of the patients diagnosed with VTE in the CRC trial received adequate thromboprophylaxis. The main reasons for this inappropriate practice were the omission of thromboprophylaxis, delayed initiation, and insufficient duration of thromboprophylaxis. We developed a specialized clinical pathway for thromboprophylaxis after CRC surgery to address these issues. CONCLUSIONS: This study offers a comprehensive nationwide evaluation of existing thromboprophylaxis practices in patients after CRC surgery in China. A specialized clinical pathway was developed to address the identified gaps and improve the quality of care. This clinical pathway incorporates explicit, tailored, detailed recommendations for thromboprophylaxis after CRC surgery.
Subject(s)
Colorectal Neoplasms , Venous Thromboembolism , Humans , Female , Male , Colorectal Neoplasms/surgery , Venous Thromboembolism/prevention & control , Venous Thromboembolism/etiology , China , Aged , Prospective Studies , Middle Aged , Risk Factors , Postoperative Complications/prevention & control , Postoperative Complications/epidemiology , Anticoagulants/therapeutic use , Anticoagulants/administration & dosage , Critical Pathways , Practice Guidelines as TopicABSTRACT
INTRODUCTION: Anastomotic leakage (AL) is defined as the failure of complete healing or disruption of the anastomosis subsequent to rectal cancer surgery, resulting in the extravasation of intestinal contents into the intra-abdominal or pelvic cavity. It is a serious complication of rectal cancer surgery, accounting for a considerable increase in morbidity and mortality. The use of fluorescence imaging technology in surgery allows surgeons to better evaluate blood perfusion. However, the conclusions of some existing studies are not consistent, so a consensus on whether the near-infrared indocyanine green (NIR-ICG) imaging system can reduce the incidence of AL is needed. METHODS: This POSTER trial is designed as a multicentre, prospective, randomised controlled clinical study adhering to the "population, interventions, comparisons, outcomes (PICO)" principles. It is scheduled to take place from August 2019 to December 2024 across eight esteemed hospitals in China. The target population consists of patients diagnosed with rectal cancer through pathological confirmation, with tumours located≤10 cm from the anal verge, eligible for laparoscopic surgery. Enrolled patients will be randomly assigned to either the intervention group or the control group. The intervention group will receive intravenous injections of ICG twice, with intraoperative assessment of anastomotic blood flow using the near-infrared NIR-ICG system during total mesorectal excision (TME) surgery. Conversely, the control group will undergo conventional TME surgery without the use of the NIR-ICG system. A 30-day follow-up period postoperation will be conducted to monitor and evaluate occurrences of AL. The primary endpoint of this study is the incidence of AL within 30 days postsurgery in both groups. The primary outcome investigators will be blinded to the application of ICG angiography. Based on prior literature, we hypothesise an AL rate of 10.3% in the control group and 3% in the experimental group for this study. With a planned ratio of 2:1 between the number of cases in the experimental and control groups, and an expected 20% lost-to-follow-up rate, the initial estimated sample size for this study is 712, comprising 474 in the experimental group and 238 in the control group. ETHICS AND DISSEMINATION: This study has been approved by Ethics committee of Beijing Friendship Hospital, Capital Medical University (approval number: 2019-P2-055-02). The results will be disseminated in major international conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04012645.
Subject(s)
Anastomotic Leak , Indocyanine Green , Laparoscopy , Rectal Neoplasms , Humans , Indocyanine Green/administration & dosage , Rectal Neoplasms/surgery , Rectal Neoplasms/diagnostic imaging , Laparoscopy/methods , Prospective Studies , Anastomotic Leak/prevention & control , Coloring Agents , Female , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Male , China , Spectroscopy, Near-Infrared/methods , Adult , Middle AgedABSTRACT
Mesenchymal stem cells (MSCs) have been recognized as a cell therapy with the potential to promote skin healing. MSCs, with their multipotent differentiation ability, can generate various cells related to wound healing, such as dermal fibroblasts (DFs), endothelial cells, and keratinocytes. In addition, MSCs promote neovascularization, cellular regeneration, and tissue healing through mechanisms including paracrine and autocrine signaling. Due to these characteristics, MSCs have been extensively studied in the context of burn healing and chronic wound repair. Furthermore, during the investigation of MSCs, their unique roles in skin aging and scarless healing have also been discovered. In this review, we summarize the mechanisms by which MSCs promote wound healing and discuss the recent findings from preclinical and clinical studies. We also explore strategies to enhance the therapeutic effects of MSCs. Moreover, we discuss the emerging trend of combining MSCs with tissue engineering techniques, leveraging the advantages of MSCs and tissue engineering materials, such as biodegradable scaffolds and hydrogels, to enhance the skin repair capacity of MSCs. Additionally, we highlight the potential of using paracrine and autocrine characteristics of MSCs to explore cell-free therapies as a future direction in stem cell-based treatments, further demonstrating the clinical and regenerative aesthetic applications of MSCs in skin repair and regeneration.
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Cellular senescence is a status of irreversible growth arrest, which can be triggered by the p53/p21cip1 and p16INK4/Rb pathways via intrinsic and external factors. Senescent cells are typically enlarged and flattened, and characterized by numerous molecular features. The latter consists of increased surfaceome, increased residual lysosomal activity at pH 6.0 (manifested by increased activity of senescence-associated beta-galactosidase [SA-ß-gal]), senescence-associated mitochondrial dysfunction, cytoplasmic chromatin fragment, nuclear lamin b1 exclusion, telomere-associated foci, and the senescence-associated secretory phenotype. These features vary depending on the stressor leading to senescence and the type of senescence. Cellular senescence plays pivotal roles in organismal aging and in the pathogenesis of aging-related diseases. Interestingly, senescence can also both promote and inhibit wound healing processes. We recently report that senescence as a programmed process contributes to normal lung development. Lung senescence is also observed in Down Syndrome, as well as in premature infants with bronchopulmonary dysplasia and in a hyperoxia-induced rodent model of this disease. Furthermore, this senescence results in neonatal lung injury. In this review, we briefly discuss the molecular features of senescence. We then focus on the emerging role of senescence in normal lung development and in the pathogenesis of bronchopulmonary dysplasia as well as putative signaling pathways driving senescence. Finally, we discuss potential therapeutic approaches targeting senescent cells to prevent perinatal lung diseases.
ABSTRACT
Adding PD-1 blockade in the neoadjuvant regimens for locally advanced rectal cancer (LARC) patients with microsatellite stable (MSS) / mismatch repair-proficient (pMMR) tumors is an attractive, but debatable strategy. This phase 2, multicenter, prospective, single-arm study enrolled patients from 6 centers from June 2021 to November 2022. Locally advanced rectal cancer (LARC, cT3-4aN0M0 and cT1-4aN1-2M0) patients aged ≥18 years with the distance from distal border of tumor to anal verge ≤10 cm (identified by Magnetic Resonance Imaging) were qualified for inclusion. The patients received long-course radiotherapy (50 Gy/25 fractions, 2 Gy/fraction, 5 days/week) and three 21-day cycles capecitabine (850-1000 mg/m2, bid, po, day1-14) and three 21-day cycles tislelizumab (200 mg, iv.gtt, day8) as neoadjuvant. Total mesorectal excision (TME) was 6-12 weeks after the end of radiotherapy to achieve radical resection. A total of 50 patients were enrolled in this study. The pathological complete response rate was 40.0% [20/50, 95% confidence interval (CI): 27.61-53.82%], while 15 (30.0%, 95% CI: 19.1-43.75%), 9 (18.0%, 95% CI: 9.77-30.8%), 2 (4.0%, 95% CI: 1.10-13.46%) patients respectively achieved grade 1, 2, and 3 tumor regression. Treatment-related adverse events (TRAEs) occurred in 28 (56.0%) LARC patients, including 26(52.0%) with grade I-II and 2 (4.0%) with grade III (1 with grade 3 immune-related colitis and 1 with grade 3 rash). PD-1 blockade plus long-course chemoradiotherapy (CRT) showed promising therapeutic effects according to pathological complete response rate and is well-tolerated in LARC patients. A larger randomized controlled study is desired to further validate the above findings.
Subject(s)
Plant Nectar , Rectal Neoplasms , Humans , Adolescent , Adult , Programmed Cell Death 1 Receptor , Prospective Studies , Rectal Neoplasms/drug therapy , Rectal Neoplasms/pathology , Chemoradiotherapy/methodsABSTRACT
Colorectal cancer has the highest mortality rate of all digestive system diseases. Considering the debate about cytokines and biases that exist in traditional observational study designs, we performed a two-sample Mendelian randomization (MR) analysis to explore the association of circulating cytokines with CRC risk. In this study, we used cytokine genetic variants from a recently published genome-wide association study (GWAS) including 14,824 European-ancestry participants. Summary-level data for colorectal cancer were obtained from genome-wide association analyses of the FinnGen consortium. In addition, we conducted independent supplementary analyses using genetic variation data of colorectal cancer and cytokines from a large public GWAS in 2021. Among 91 circulating factors, we only found IL-12B to be significantly associated with CRC risk (odds ratio [OR]: 1.19; 95% confidence interval [CI]: 1.00-1.42; p = .046). We used 2021 data for analysis and found that higher Interleukin-12p70 levels (IL-12p70) were revealed to have a significant positive association with CRC risk (OR: 1.27; 95% CI: 1.13-1.43; p < 1.22 × 10-3). Moreover, CRC was suggestively correlated with an elevated level of vascular endothelial growth factor (VEGF) (OR: 1.17; 95% CI: 1.02-1.35; p = .026), macrophage colony-stimulating factor (M-CSF) (OR: 0.85; 95% CI: 0.76-0.96; p = .005), IL-13 (OR: 1.15; 95% CI: 1.02-1.30; p = .028), IL-10 (OR: 1.23; 95% CI: 1.01-1.49; p = .037), and IL-7 (OR: 1.19; 95% CI: 1.02-1.39; p = .024). Our MR studies support that one cytokine IL-12 is significantly associated with CRC risk and that five cytokines VEGF, M-CSF, IL-13, IL-10, and IL-7 are associated with CRC risk.
Subject(s)
Colorectal Neoplasms , Genome-Wide Association Study , Mendelian Randomization Analysis , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/blood , Cytokines/blood , Cytokines/genetics , Polymorphism, Single Nucleotide , Genetic Predisposition to Disease , Risk Factors , Interleukin-12 Subunit p40/genetics , Interleukin-12 Subunit p40/blood , Vascular Endothelial Growth Factor A/blood , Vascular Endothelial Growth Factor A/genetics , Male , Female , Interleukin-10/blood , Interleukin-10/geneticsABSTRACT
TANK-binding kinase 1 (TBK1) is a potential therapeutic target in multiple cancers, including clear cell renal cell carcinoma (ccRCC). However, targeting TBK1 in clinical practice is challenging. One approach to overcome this challenge would be to identify an upstream TBK1 regulator that could be targeted therapeutically in cancer specifically. In this study, we perform a kinome-wide small interfering RNA (siRNA) screen and identify doublecortin-like kinase 2 (DCLK2) as a TBK1 regulator in ccRCC. DCLK2 binds to and directly phosphorylates TBK1 on Ser172. Depletion of DCLK2 inhibits anchorage-independent colony growth and kidney tumorigenesis in orthotopic xenograft models. Conversely, overexpression of DCLK2203, a short isoform that predominates in ccRCC, promotes ccRCC cell growth and tumorigenesis in vivo. Mechanistically, DCLK2203 elicits its oncogenic signaling via TBK1 phosphorylation and activation. Taken together, these results suggest that DCLK2 is a TBK1 activator and potential therapeutic target for ccRCC.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinogenesis/genetics , Carcinoma, Renal Cell/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Cell Transformation, Neoplastic/genetics , Doublecortin-Like Kinases , Gene Expression Regulation, Neoplastic , Kidney Neoplasms/metabolism , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolismABSTRACT
BACKGROUND: The ectoparasitic wasp Habrobracon hebetor (Hymenoptera, Braconidae) can parasitize various species of lepidopteran pests. To maximize its potential for biological control, it is necessary to investigate its gene function through genome engineering. RESULTS: To test the effectiveness of genome engineering system in H. hebetor, we injected the mixture of clustered regularly interspaced short palindromic repeats (CRISPR) -associated (Cas) 9 protein and single guide RNA(s) targeting gene white into embryos. The resulting mutants display a phenotype of eye pigment loss. The phenotype was caused by small indel and is heritable. Then, we compared some biological parameters between wildtype and mutant, and found there were no significant differences in other parameters except for the offspring female rate and adult longevity. In addition, cocoons could be used to extract genomic DNA for genotype during the gene editing process without causing unnecessary harm to H. hebetor. CONCLUSION: Our results demonstrate that the CRISPR/Cas9 system can be used for H. hebetor genome editing and it does not adversely affect biological parameters of the parasitoid wasps. We also provide a feasible non-invasive genotype detection method using genomic DNA extracted from cocoons. Our study introduces a novel tool and method for studying gene function in H. hebetor, and may contribute to better application of H. hebetor in biocontrol. © 2023 Society of Chemical Industry.
Subject(s)
Wasps , Animals , Female , Wasps/metabolism , CRISPR-Cas Systems , RNA, Guide, CRISPR-Cas Systems , Mutagenesis , DNAABSTRACT
Introduction: It has been a decade since the first patient with colon cancer underwent colectomy by hybrid transvaginal natural orifice transluminal endoscopic surgery (hvNOTES). However, the efficacy and safety of this procedure is not well established. Methods: This study is an open-label, multicenter, single-arm, phase 2 trial undertaken at six centers in China. Female patients aged over 18 years and below 80 years old with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, with pathologically proven, resectable, cT1-3N0-2M0 disease who have previously untreated colon cancer are eligible for inclusion. The primary endpoint is a composite of major intraoperative and postoperative complications (greater than grade III, the Common Terminology Criteria for Adverse Events [CTCAE], version 5.0). Secondary endpoints include conversion to laparoscopic or open surgery, postoperative concentration of C-Reactive Protein and procalcitonine, complete pathological assessment of complete mesocolic excision specimens, postoperative pain, amount of narcotic pain medication administered, time to first flatus after surgery, number of harvested lymph nodes, R0 resection rate, length of hospital stay, sexual function assessment, quality of recovery, satisfaction with surgical scars, quality of life, postoperative recurrence patterns, relapse-free survival, and overall survival. Ethics and dissemination: The study was approved by the Research Ethics Committee, Renmin Hospital of Wuhan University, China, number: WDRY2022-K053. All patients will receive written information of the trial and provide informed consent before enrollment. The results of this trial will be disseminated in academic conferences and peer-reviewed medical journals.Trial registration number NCT04048421.
ABSTRACT
INTRODUCTION: Recent preclinical studies have discovered unique synergism between radiotherapy and immune checkpoint inhibitors, which has already brought significant survival benefit in lung cancer. In locally advanced rectal cancer (LARC), neoadjuvant radiotherapy plus immune checkpoint inhibitors have also achieved surprisingly high pathological complete response (pCR) rates even in proficient mismatch-repair patients. As existing researches are all phase 2, single-cohort trials, we aim to conduct a randomised, controlled trial to further clarify the efficacy and safety of this novel combination therapy. METHODS AND ANALYSIS: Eligible patients with LARC are randomised to three arms (two experiment arms, one control arm). Patients in all arms receive long-course radiotherapy plus concurrent capecitabine as neoadjuvant therapy, as well as radical surgery. Distinguishingly, patients in arm 1 also receive anti-PD-1 (Programmed Death 1) treatment starting at Day 8 of radiation (concurrent plan), and patients in arm 2 receive anti-PD-1 treatment starting 2 weeks after completion of radiation (sequential plan). Tislelizumab (anti-PD-1) is scheduled to be administered at 200 mg each time for three consecutive times, with 3-week intervals. Randomisation is stratified by different participating centres, with a block size of 6. The primary endpoint is pCR rate, and secondary endpoints include neoadjuvant-treatment-related adverse event rate, as well as disease-free and overall survival rates at 2, 3 and 5 years postoperation. Data will be analysed with an intention-to-treat approach. ETHICS AND DISSEMINATION: This protocol has been approved by the institutional ethical committee of Beijing Friendship Hospital (the primary centre) with an identifying serial number of 2022-P2-050-01. Before publication to peer-reviewed journals, data of this research will be stored in a specially developed clinical trial database. TRIAL REGISTRATION NUMBER: NCT05245474.
Subject(s)
Neoplasms, Second Primary , Rectal Neoplasms , Humans , Neoadjuvant Therapy , Immune Checkpoint Inhibitors/therapeutic use , Chemoradiotherapy , Combined Modality Therapy , Rectal Neoplasms/therapy , Randomized Controlled Trials as Topic , Multicenter Studies as Topic , Clinical Trials, Phase II as TopicABSTRACT
BACKGROUND & AIMS: The benefit of radiotherapy for rectal cancer is based largely on a balance between a decrease in local recurrence and an increase in bowel dysfunction. Predicting postoperative disability is helpful for recovery plans and early intervention. We aimed to develop and validate a risk model to improve the prediction of major bowel dysfunction after restorative rectal cancer resection with neoadjuvant radiotherapy using perioperative features. METHODS: Eligible patients more than 1 year after restorative resection following radiotherapy were invited to complete the low anterior resection syndrome (LARS) score at 3 national hospitals in China. Clinical characteristics and imaging parameters were assessed with machine learning algorithms. The post-radiotherapy LARS prediction model (PORTLARS) was constructed by means of logistic regression on the basis of key factors with proportional weighs. The accuracy of the model for major LARS prediction was internally and externally validated. RESULTS: A total of 868 patients reported a mean LARS score of 28.4 after an average time of 4.7 years since surgery. Key predictors for major LARS included the length of distal rectum, anastomotic leakage, proximal colon of neorectum, and pathologic nodal stage. PORTLARS had a favorable area under the curve for predicting major LARS in the internal dataset (0.835; 95% CI, 0.800-0.870, n = 521) and external dataset (0.884; 95% CI, 0.848-0.921, n = 347). The model achieved both sensitivity and specificity >0.83 in the external validation. In addition, PORTLARS outperformed the preoperative LARS score for prediction of major events. CONCLUSIONS: PORTLARS could predict major bowel dysfunction after rectal cancer resection following radiotherapy with high accuracy and robustness. It may serve as a useful tool to identify patients who need additional support for long-term dysfunction in the early stage. CLINICALTRIALS: gov, number NCT05129215.
Subject(s)
Gastrointestinal Diseases , Intestinal Diseases , Rectal Neoplasms , Humans , Rectum/diagnostic imaging , Rectum/surgery , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/surgery , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Low Anterior Resection SyndromeABSTRACT
BACKGROUND: Behavior-based manipulation is an essential part of Drosophila integrated pest management (IPM). Effective compounds are useful for improving the efficiency of baits and the development of attract-and-kill or push-pull strategies to manage Drosophila populations. Here, we investigated the olfactory behavior of two Drosophila species, as well as their pupal parasitoid, to volatiles from bananas, for the identification of effective compounds to control fly populations. RESULTS: The results showed that overripe bananas were most attractive to both flies, with a higher attraction index (AI) in Drosophila melanogaster than in Drosophila suzukii. The profiles of volatile organic compounds (VOCs) from bananas with three different ripening stages were compared, and six VOCs were selected for behavioral tests. D. suzukii showed significantly different responses to isoamyl alcohol with D. melanogaster. The effects of ethyl butyrate and ethyl isovalerate on the two flies were dose-dependent, with lower concentrations acting as repellent and higher concentrations acting as attractant. Isoamyl acetate, isoamyl butyrate and isoamyl isovalerate (0.005-0.05% v/v) were attractive to both flies. The parasitoid wasp Pachycrepoidus vindemmiae was repelled by isoamyl alcohol and ethyl butyrate, and attracted by ethyl isovalerate, but showed no significant response to isoamyl acetate, isoamyl butyrate and isoamyl isovalerate at the tested concentration. CONCLUSION: This study indicated that the behavioral response of Drosophila to the odor of chemical compounds is dose-dependent. Isoamyl alcohol and isoamyl acetate at certain concentrations could be used as repellents, whereas ethyl isovalerate as an attractant in control strategy design for D. suzukii. © 2023 Society of Chemical Industry.
Subject(s)
Insect Repellents , Musa , Animals , Drosophila/physiology , Drosophila melanogaster , Butyrates/pharmacology , Insect Repellents/pharmacologyABSTRACT
BACKGROUND: Venous thromboembolism (VTE) is a common and serious complication after colorectal cancer (CRC) surgery. Few large-sample studies have reported VTE incidence and management status after CRC surgery in China. This study aimed to investigate the incidence and prevention of VTE in Chinese patients after CRC surgery, identify risk factors for developing VTE, and construct a new scoring system for clinical decision-making and care planning. METHODS: Participants were recruited from 46 centers in 17 provinces in China. Patients were followed up for 1 month postoperatively. The study period was from May 2021 to May 2022. The Caprini score risk stratification and VTE prevention and incidence were recorded. The predictors of the occurrence of VTE after surgery were identified by multivariate logistic regression analysis, and a prediction model (CRC-VTE score) was developed. RESULTS: A total of 1836 patients were analyzed. The postoperative Caprini scores ranged from 1 to 16 points, with a median of 6 points. Of these, 10.1% were classified as low risk (0-2 points), 7.4% as moderate risk (3-4 points), and 82.5% as high risk (≥5 points). Among these patients, 1210 (65.9%) received pharmacological prophylaxis, and 1061 (57.8%) received mechanical prophylaxis. The incidence of short-term VTE events after CRC surgery was 11.2% (95% CI 9.8-12.7), including deep venous thrombosis (DVT) (11.0%, 95% CI 9.6-12.5) and pulmonary embolism (PE) (0.2%, 95% CI 0-0.5). Multifactorial analysis showed that age (≥70 years), history of varicose veins in the lower extremities, cardiac insufficiency, female sex, preoperative bowel obstruction, preoperative bloody/tarry stool, and anesthesia time at least 180 min were independent risk factors for postoperative VTE. The CRC-VTE model was developed from these seven factors and had good VTE predictive performance ( C -statistic 0.72, 95% CI 0.68-0.76). CONCLUSIONS: This study provided a national perspective on the incidence and prevention of VTE after CRC surgery in China. The study offers guidance for VTE prevention in patients after CRC surgery. A practical CRC-VTE risk predictive model was proposed.
Subject(s)
Colorectal Neoplasms , Pulmonary Embolism , Venous Thromboembolism , Humans , Female , Aged , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control , Prospective Studies , Incidence , East Asian People , Risk Assessment , Risk Factors , Pulmonary Embolism/complications , Colorectal Neoplasms/surgery , Colorectal Neoplasms/complications , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/prevention & controlABSTRACT
Habrobracon hebetor is a parasitoid wasp capable of infesting many lepidopteran larvae. It uses venom proteins to immobilize host larvae and prevent host larval development, thus playing an important role in the biocontrol of lepidopteran pests. To identify and characterize its venom proteins, we developed a novel venom collection method using an artificial host (ACV), i.e., encapsulated amino acid solution in paraffin membrane, allowing parasitoid wasps to inject venom. We performed protein full mass spectrometry analysis of putative venom proteins collected from ACV and venom reservoirs (VRs) (control). To verify the accuracy of proteomic data, we also collected venom glands (VGs), Dufour's glands (DGs) and ovaries (OVs), and performed transcriptome analysis. In this paper, we identified 204 proteins in ACV via proteomic analysis; compared ACV putative venom proteins with those identified in VG, VR, and DG via proteome and transcriptome approaches; and verified a set of them using quantitative real-time polymerase chain reaction. Finally, 201 ACV proteins were identified as potential venom proteins. In addition, we screened 152 and 148 putative venom proteins identified in the VG transcriptome and the VR proteome against those in ACV, and found only 26 and 25 putative venom proteins, respectively, were overlapped with those in ACV. Altogether, our data suggest proteome analysis of ACV in combination with proteome-transcriptome analysis of other organs/tissues will provide the most comprehensive identification of true venom proteins in parasitoid wasps.