The AP-2 Family of Transcription Factors-Still Undervalued Regulators in Gastroenterological Disorders.

Activating enhancer-binding protein 2 (AP-2) is a family of transcription factors (TFs) that play crucial roles in regulating embryonic and oncogenic development. In addition to splice isoforms, five major family members encoded by the TFAP2A/B/C/D/E genes have been identified in humans, i.e., AP-2α/ß/γ/δ/ε. In general, the first three TFs have been studied more thoroughly than AP-2δ or AP-2ε. Currently, there is a relatively limited body of literature focusing on the AP-2 family in the context of gastroenterological research, and a comprehensive overview of the existing knowledge and recommendations for further research directions is lacking. Herein, we have collected available gastroenterological data on AP-2 TFs, discussed the latest medical applications of each family member, and proposed potential future directions. Research on AP-2 in gastrointestinal tumors has predominantly been focused on the two best-described family members, AP-2α and AP-2γ. Surprisingly, research in the past decade has highlighted the importance of AP-2ε in the drug resistance of gastric cancer (GC) and colorectal cancer (CRC). While numerous questions about gastroenterological disorders await elucidation, the available data undoubtedly open avenues for anti-cancer targeted therapy and overcoming chemotherapy resistance. In addition to gastrointestinal cancers, AP-2 family members (primarily AP-2ß and marginally AP-2γ) have been associated with other health issues such as obesity, type 2 diabetes, liver dysfunction, and pseudo-obstruction. On the other hand, AP-2δ has been poorly investigated in gastroenterological disorders, necessitating further research to delineate its role. In conclusion, despite the limited attention given to AP-2 in gastroenterology research, pivotal functions of these transcription factors have started to emerge and warrant further exploration in the future.

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Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by symptoms such as abdominal pain, diarrhea, constipation, and indigestion. Given its unclear etiology and pathogenesis, and the absence of specific biomarkers, clinical diagnosis and treatment of IBS continue to pose significant challenges. In recent years, metabolomics technology, known for its non-invasive, high-throughput, high-precision, and highly reproducible features, has been widely applied in the diagnosis, treatment, and prognosis of various diseases. Therefore, metabolomics technology is expected to offer novel insights and methodologies for the biological mechanism research, diagnosis, and treatment of IBS. This article reviews recent advancements in the application of metabolomics to IBS, exploring its potential value in the clinical diagnosis and treatment of children with this condition.

Nanodelivery Optimization of IDO1 Inhibitors in Tumor Immunotherapy: Challenges and Strategies.

Tryptophan (Trp) metabolism plays a vital role in cancer immunity. Indoleamine 2.3-dioxygenase 1 (IDO1), is a crucial enzyme in the metabolic pathway by which Trp is degraded to kynurenine (Kyn). IDO1-mediated Trp metabolites can inhibit tumor immunity and facilitate immune evasion by cancer cells; thus, targeting IDO1 is a potential tumor immunotherapy strategy. Recently, numerous IDO1 inhibitors have been introduced into clinical trials as immunotherapeutic agents for cancer treatment. However, drawbacks such as low oral bioavailability, slow onset of action, and high toxicity are associated with these drugs. With the continuous development of nanotechnology, medicine is gradually entering an era of precision healthcare. Nanodrugs carried by inorganic, lipid, and polymer nanoparticles (NPs) have shown great potential for tumor therapy, providing new ways to overcome tumor diversity and improve therapeutic efficacy. Compared to traditional drugs, nanomedicines offer numerous significant advantages, including a prolonged half-life, low toxicity, targeted delivery, and responsive release. Moreover, based on the physicochemical properties of these nanomaterials (eg, photothermal, ultrasonic response, and chemocatalytic properties), various combination therapeutic strategies have been developed to synergize the effects of IDO1 inhibitors and enhance their anticancer efficacy. This review is an overview of the mechanism by which the Trp-IDO1-Kyn pathway acts in tumor immune escape. The classification of IDO1 inhibitors, their clinical applications, and barriers for translational development are discussed, the use of IDO1 inhibitor-based nanodrug delivery systems as combination therapy strategies is summarized, and the issues faced in their clinical application are elucidated. We expect that this review will provide guidance for the development of IDO1 inhibitor-based nanoparticle nanomedicines that can overcome the limitations of current treatments, improve the efficacy of cancer immunotherapy, and lead to new breakthroughs in the field of cancer immunotherapy.

Jin-Gu-Lian Capsule Did Not Significantly Improve Clinical Value in Rheumatoid Arthritis Therapy: A Real-World Study.

Purpose: To investigate the clinical value of adding Jin-gu-lian (JGL) capsules into rheumatoid arthritis (RA) treatment by examining its impact on disease activity and quality of life (QoL) through a real-world study (RWS). Patients and methods: RWS was conducted to compare the inflammatory markers, including IgM-RF, ESR, and CRP, between RA patients treated with only Western medicine (reference group) and Western medicine plus JGL (study group) during one-year follow-up. The clinical data was acquired from the hospital information system (HIS). Telephone call-based follow-up on QoL (SF-36) and accompanying symptoms, including gastrointestinal complaints, attacks of pneumonia, herpes zoster, URTIs, UTIs, and LTBIs. Finally, the anti-rheumatic drugs given to both groups were also compared. RWS was further validated for its feasibility by performing studies with hydroxychloroquine (HCQ) treatment, which is a commonly used anti-rheumatic drug for RA with mild effect. Results: The study group failed to show a significant effect on inflammatory markers, especially on the CRP levels, indicating no additional clinical value of supplementing with JGL. Similarly, at the endpoint, no significant differences between the two groups on QoL and related symptoms were observed. Our study suggests that the patients in the study group might need more anti-rheumatic drugs to fill the treatment insufficiency, and the application ratio of NSAIDs would be significantly higher than the reference group. By conducting this study on HCQ treatment, the positive aspects of controlling disease activity and reducing NSAIDs application were found, which demonstrates the utility of performing the RWS to evaluate the effect of JGL. Conclusion: Adding JGL did not significantly improve the clinical efficacy of RA treatment by this RWS. Folk herbal prescriptions such as JGL are suggested to underwent strict clinical trials before application.

Predictive value of CXCL1+_FAP+ phenotype in CAFs for distant metastasis and its correlation with PD-L1 expression in locoregionally advanced nasopharyngeal carcinoma patients.

OBJECTIVE: There is a lack of effective biomarkers for predicting the distant metastasis in nasopharyngeal carcinoma (NPC). We aimed to explore the expression of FAP+Cancer-associated fibroblasts (CAFs) derived CXCL1 in NPC and its predictive values for distant metastasis and correlation with PD-L1 expression. MATERIALS AND METHODS: A total of 345 patients with locoregionally advanced NPC were retrospectively enrolled (the training cohort: the validation cohort = 160:185). Co-expression of CXCL1 and FAP and the expression of PD-L1 were detected by multi-immunofluorescence staining and immunohistochemistry, respectively. The primary end-point was distant metastasis-free survival (DMFS). The Kaplan-Meier method was used to calculate the survival. The Cox proportional hazards model was used to assess prognostic risk factors. RESULTS: A novel CXCL1+_FAP+ phenotype in CAFs was identified in NPC and then used to divide patients into low and high risk groups. Both in the training cohort and validation cohort, patients in the high risk group had poorer DMFS, overall survival (OS), progression-free survival (PFS) and locoregional relapse-free survival (LRFS) than patients in the low risk group. Multivariate analysis revealed CXCL1+_FAP+ phenotype was an independent prognostic factor for DMFS, OS, PFS and LRFS. Further results showed patients in the high risk group had higher PD-L1 expression than those in the low risk group. CONCLUSION: Our study showed CXCL1+_FAP+ phenotype in CAFs could effectively classified locoregionally advanced NPC patients into different risk groups for distant metastasis and might be a potential biomarker for anti-PD-1/PD-L1 immunotherapy.

Preoperative prediction of microvascular invasion: new insights into personalized therapy for early-stage hepatocellular carcinoma.

Owing to advances in diagnosis and treatment methods over past decades, a growing number of early-stage hepatocellular carcinoma (HCC) diagnoses has enabled a greater of proportion of patients to receive curative treatment. However, a high risk of early recurrence and poor prognosis remain major challenges in HCC therapy. Microvascular invasion (MVI) has been demonstrated to be an essential independent predictor of early recurrence after curative therapy. Currently, biopsy is not generally recommended before treatment to evaluate MVI in HCC according clinical guidelines due to sampling error and the high risk of tumor cell seeding following biopsy. Therefore, the postoperative histopathological examination is recognized as the gold standard of MVI diagnosis, but this lagging indicator greatly impedes clinicians in selecting the optimal effective treatment for prognosis. As imaging can now noninvasively and completely assess the whole tumor and host situation, it is playing an increasingly important role in the preoperative assessment of MVI. Therefore, imaging criteria for MVI diagnosis would be highly desirable for optimizing individualized therapeutic decision-making and achieving a better prognosis. In this review, we summarize the emerging image characteristics of different imaging modalities for predicting MVI. We also discuss whether advances in imaging technique have generated evidence that could be practice-changing and whether advanced imaging techniques will revolutionize therapeutic decision-making of early-stage HCC.

Distinct oral-associated gastric microbiota and Helicobacter pylori communities for spatial microbial heterogeneity in gastric cancer.

The gastric microbial community plays a fundamental role in gastric cancer (GC), and the two main anatomical subtypes of GC, non-cardia and cardia GC, are associated with different risk factors (Helicobacter pylori for non-cardia GC). To decipher the different microbial spatial communities of GC, we performed a multicenter retrospective analysis to characterize the gastric microbiota in 223 GC patients, including H. pylori-positive or -negative patients, with tumors and paired adjacent normal tissues, using third-generation sequencing. In the independent validation cohort, both dental plaque and GC tumoral tissue samples were collected and sequenced. The prevalence of H. pylori and oral-associated bacteria was verified using fluorescence in situ hybridization (FISH) assays in GC tumoral tissues and matched nontumoral tissues. We found that the vertical distribution of the gastric microbiota, at the upper, middle, and lower third sites of GC, was likely an important factor causing microbial diversity in GC tumor tissues. The oral-associated microbiota cluster, which included Veillonella parvula, Streptococcus oralis, and Prevotella intermedia, was more abundant in the upper third of the GC. However, H. pylori was more abundant in the lower third of the GC and exhibited a significantly high degree of microbial correlation. The oral-associated microbiota module was co-exclusive with H. pylori in the lower third site of the GC tumoral tissue. Importantly, H. pylori-negative GC patients with oral-associated gastric microbiota showed worse overall survival, while the increase in microbial abundance in H. pylori-positive GC patients showed no difference in overall survival. The prevalence of V. parvula in both the dental plaque and GC tissue samples was concordant in the independent validation phase. We showed that the oral-associated species V. parvula and S. oralis were correlated with overall survival. Our study highlights the roles of the oral-associated microbiota in the upper third of the GC. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for H. pylori-negative GCs. IMPORTANCE: Our study highlights the roles of the oral-associated microbiota in the upper third of gastric cancer (GC).We showed that the oral-associated species Veillonella parvula and Streptococcus oralis were correlated with overall survival. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for Helicobacter pylori-negative GCs.

The impact of frailty on clinical outcomes of older patients undergoing enhanced recovery after lumbar fusion surgery: a prospective cohort study.

BACKGROUND: Frailty is recognized as a surrogate for physiological age and has been established as a valid and independent predictor of postoperative morbidity, mortality, and complications. Enhanced recovery after surgery (ERAS) can enhance surgical safety by minimizing stress responses in frail patients, enabling surgeons to discharge patients earlier. However, the question of whether and to what extent the frailty impacts the post-ERAS outcomes in older patients remains. MATERIALS AND METHODS: An evidence-based ERAS program was implemented in our center from January 2019. This is a prospective cohort study of patients aged ≥75 years who underwent open transforaminal lumbar interbody fusion (TLIF) for degenerative spine disease from April 2019 to October 2021. Frailty was assessed with the Fried frailty scale (FP scale), and patients were categorized as non/prefrail (FP 0-2) or frail (FP ≥ 3). The preoperative variables, operative data, postoperative outcomes, and follow-up information were compared between the two groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for 90-day major complications and prolonged length of hospital stay after surgery. RESULTS: A total of 245 patients (age of 79.8±3.4 year) who had a preoperative FP score recorded and underwent scheduled TLIF surgery were included in the final analysis. Comparisons between nonfrail and prefrail/frail patients revealed no significant difference in age, sex, and surgery-related variables. Even after adjusting for multiple comparisons, the association between Fried frailty and ADL-dependency, IADL-dependency, and malnutrition remained significant. Preoperative frailty was associated with increased rates of postoperative adverse events. A higher CCI grade was an independent predictor for 90-day major complications, while Fried frailty and MNA-SF scores <12 were predictive of poor postoperative recovery. CONCLUSION: Frail older patients had more adverse post-ERAS outcomes after TLIF compared to non/prefrail older patients. Continued research and multidisciplinary collaboration will be essential to refine and optimize protocols for surgical care in frail older adults.

YAP/TAZ Signaling Enhances Angiogenesis of Retinal Microvascular Endothelial Cells in a High-Glucose Environment.

PURPOSE: Diabetic retinopathy (DR) is a major cause of irreversible blindness in the working-age population. Neovascularization is an important hallmark of advanced DR. There is evidence that Yes-associated protein (YAP)/transcriptional co-activator with a PDZ binding domain (TAZ) plays an important role in angiogenesis and that its activity is regulated by vascular endothelial growth factor (VEGF). Therefore, the aim of this study was to investigate the effect of YAP/TAZ-VEGF crosstalk on the angiogenic capacity of human retinal microvascular endothelial cells (hRECs) in a high-glucose environment. METHODS: The expression of YAP and TAZ of hRECs under normal conditions, hypertonic conditions and high glucose were observed. YAP overexpression (OE-YAP), YAP silencing (sh-YAP), VEGF overexpression (OE-VEGF) and VEGF silencing (sh-VEGF) plasmids were constructed. Cell counting kit-8 assay was performed to detect cells proliferation ability, transwell assay to detect cells migration ability, and tube formation assay to detect tube formation ability. The protein expression of YAP, TAZ, VEGF, matrix metalloproteinase (MMP)-8, MMP-13, vessel endothelium (VE)-cadherin and alpha smooth muscle actin (α-SMA) was measured by western blot. RESULTS: The proliferation of hRECs was significantly higher in the high glucose group compared with the normal group, as well as the protein expression of YAP and TAZ (p < 0.01). YAP and VEGF promoted the proliferation, migration and tube formation of hRECs in the high glucose environment (p < 0.01), and increased the expression of TAZ, VEGF, MMP-8, MMP-13 and α-SMA while reducing the expression of VE-cadherin (p < 0.01). Knockdown of YAP effectively reversed the above promoting effects of OE-VEGF (p < 0.01) and overexpression of YAP significantly reversed the inhibition effects of sh-VEGF on above cell function (p < 0.01). CONCLUSION: In a high-glucose environment, YAP/TAZ can significantly promote the proliferation, migration and tube formation ability of hRECs, and the mechanism may be related to the regulation of VEGF expression.

Optimal timing of surgery for gastric cancer after neoadjuvant chemotherapy: a systematic review and meta-analysis.

BACKGROUND: Following neoadjuvant chemotherapy, surgical resection is one of the most preferred treatment options for locally advanced gastric cancer patients. However, the optimal time interval between chemotherapy and surgery is unclear. This review aimed to identify the optimal time interval between neoadjuvant chemotherapy and surgery for advanced gastric cancer. METHODS: Beginning on November 12, 2022, we searched the PubMed, Cochrane Library, Web of Science databases, and Embase.com databases for relevant English-language research. Two authors independently screened the studies, assessed their quality, extracted the data, and analyzed the results. The primary goal was to investigate the relationship between the time interval to surgery (TTS) and long-term survival outcomes for patients. This study has been registered with PROSPERO (CRD42022365196). RESULTS: After an initial search of 4880 articles, the meta-analysis review ultimately included only five retrospective studies. Ultimately, this meta-analysis included 1171 patients, of which 411 patients had TTS of < 4 weeks, 507 patients had TTS of 4-6 weeks, and 253 patients had TTS of > 6 weeks. In survival analysis, patients with TTS of > 6 weeks had poorer overall survival outcomes than patients with TTS of 4-6 weeks (HR = 1.34, 95% CI: 1.03-1.75, P = 0.03). No significant differences were found in terms of disease-free survival the groups. CONCLUSION: Based on the current clinical evidence, patients with locally advanced gastric cancer may benefit better with a TTS of 4-6 weeks; however, this option still needs additional study.

Relation of lumbar intervertebral disc height and severity of disc degeneration based on Pfirrmann scores.

Background: Disc height (DH) change is considered one of the most critical factors in assessing intervertebral disc degeneration (IVD). Pfirrmann et al. developed a scoring system for disc degeneration evaluation based on changes in DH in magnetic resonance imaging (MRI). While the relationship between DH measurements and Pfirrmann scores for disc degeneration has been explored, the validity of different DH measuring techniques or their connection with disc degeneration is yet uncertain. The present study investigates intra-rater and inter-rater agreement and reliability of different DH measurement methods on MRI and evaluates the relationship between different DH measurement methods and Pfirrmann scores of IVD degeneration, as well as between different Pfirrmann scores and clinical outcomes. Methods: Adult patients with MRI scans of the lumbar spine were recruited. Eight DH measuring techniques were tested for intra-rater and inter-rater agreement and reliability. Bland and Altman's Limits of Agreement (LOA) was used to evaluate intra-rater and inter-rater agreements. Intra-rater and inter-rater reliability were evaluated using intra-class correlations (ICC) with 95 % confidence intervals (95 % CI). The association between DH and Pfirrmann scores was examined using one-way ANOVA. Results: Excellent intra-rater reliability was reported for 332 participants on DH (ranging from 0.912 (0.901, 0.923) to 0.973 (0.964, 0.981) and from 0.902 (0.892, 0.915) to 0.975 (0.962, 0.985) by two independent raters). All measuring methods had high intra-rater agreement, except for methods 4 and 5. All methods had good-to-excellent of inter-rater reliability on DH (ICCs ranging from 0.812 (0.795, 0.828) to 0.995 (0.994, 0.995)) except for the posterior disc material length of method 5 (ICC 0.740 (0.718, 0.761)). Methods 1 to 6 for evaluating DH in patients with spondylolisthesis had poor inter-rater reliability. The IVD levels with grades IV and V in Pfirrmann scores had significantly lower DH than the IVD levels with grades I to III in Pfirrmann scores. IVD levels with grades IV and V in Pfirrmann scores had significantly higher VAS and ODI than IVD levels with grades I in Pfirrmann scores. Conclusion: A good-to-excellent intra-rater and inter-rater reliability was achieved on most DH measuring methods on MRI following a standardized and structured protocol. However, small anatomical structures and different tissue borders could influence measurements. Additionally, DH can differentiate between grade IV and V Pfirrmann scores, and severe IVD degeneration (IV and V Pfirrmann) is linked to clinical outcomes.

Role of the gut microbiota in anticancer therapy: from molecular mechanisms to clinical applications.

In the past period, due to the rapid development of next-generation sequencing technology, accumulating evidence has clarified the complex role of the human microbiota in the development of cancer and the therapeutic response. More importantly, available evidence seems to indicate that modulating the composition of the gut microbiota to improve the efficacy of anti-cancer drugs may be feasible. However, intricate complexities exist, and a deep and comprehensive understanding of how the human microbiota interacts with cancer is critical to realize its full potential in cancer treatment. The purpose of this review is to summarize the initial clues on molecular mechanisms regarding the mutual effects between the gut microbiota and cancer development, and to highlight the relationship between gut microbes and the efficacy of immunotherapy, chemotherapy, radiation therapy and cancer surgery, which may provide insights into the formulation of individualized therapeutic strategies for cancer management. In addition, the current and emerging microbial interventions for cancer therapy as well as their clinical applications are summarized. Although many challenges remain for now, the great importance and full potential of the gut microbiota cannot be overstated for the development of individualized anti-cancer strategies, and it is necessary to explore a holistic approach that incorporates microbial modulation therapy in cancer.

The effect of sagittal alignment, coronal balance, and segmental stability on preoperative patient-reported outcomes in patients with degenerative lumbar spondylolisthesis.

OBJECTIVE: The aim of this study was to investigate the association between spinal alignment and preoperative patient-reported outcomes (PROs) in patients with degenerative lumbar spondylolisthesis (DLS) and to identify the independent risk factors for worse preoperative PROs. METHODS: In total, 101 patients suffering from DLS were retrospectively studied within a single medical center. Age, sex, height, weight, and body mass index were uniformly recorded. PRO-related indicators include the Oswestry Disability Index (ODI), the Japanese Orthopedic Association's (JOA) score, and the visual analog scale (VAS) for back and leg pain. Sagittal alignment, coronal balance, and stability of the L4/5 level were evaluated through whole-spine anteroposterior and lateral radiographs and dynamic lumbar X-ray. RESULTS: Increasing age (P = 0.005), higher sagittal vertical axis (SVA) (P < 0.001), and global coronal imbalance (GCI) (P = 0.023) were independent risk factors for higher ODI. Patients with GCI had lower JOA scores (P = 0.001) than those with balanced coronal alignment. Unstable spondylolisthesis (P < 0.001) and GCI (P = 0.009) were two vital predictors of VAS-back pain. Increasing age (P = 0.031), local coronal imbalance (LCI) (P < 0.001), and GCI (P < 0.001) were associated with higher VAS-leg pain. Moreover, patients with coronal imbalance also exhibited significant sagittal malalignment based on the subgroup analysis. CONCLUSION: DLS patients with higher SVA, unstable spondylolistheses, a combination of LCI/GCI, or increasing age were predisposed to have more severe subjective symptoms before surgery.

Nanosecond pulsed electric field ablates rabbit VX2 liver tumors in a non-thermal manner.

BACKGROUND: Liver tumor remains an important cause of cancer-related death. Nanosecond pulsed electric fields (nsPEFs) are advantageous in the treatment of melanoma and pancreatic cancer, but their therapeutic application on liver tumors need to be further studied. METHODS: Hep3B cells were treated with nsPEFs. The biological behaviors of cells were detected by Cell Counting Kit-8, 5-ethynyl-20-deoxyuridine, and transmission electron microscopy (TEM) assays. In vivo, rabbit VX2 liver tumor models were ablated by ultrasound-guided nsPEFs and radiofrequency ablation (RFA). Contrast-enhanced ultrasound (CEUS) was used to evaluate the ablation effect. HE staining and Masson staining were used to evaluate the tissue morphology after ablation. Immunohistochemistry was performed to determine the expression of Ki67, proliferating cell nuclear antigen, and α-smooth muscle actin at different time points after ablation. RESULTS: The cell viability of Hep3B cells was continuously lower than that of the control group within 3 days after pulse treatment. The proliferation of Hep3B cells was significantly affected by nsPEFs. TEM showed that Hep3B cells underwent significant morphological changes after pulse treatment. In vivo, CEUS imaging showed that nsPEFs could completely ablate model rabbit VX2 liver tumors. After nsPEFs ablation, the area of tumor fibrosis and the expression of Ki67, proliferating cell nuclear antigen, and α-smooth muscle actin were decreased. However, after RFA, rabbit VX2 liver tumor tissue showed complete necrosis, but the expression of PCNA and α-smooth muscle actin did not decrease compared to the tumor group. CONCLUSIONS: nsPEFs can induce Hep3B cells apoptosis and ablate rabbit VX2 liver tumors in a non-thermal manner versus RFA. The ultrasound contrast agent can monitor immediate effect of nsPEF ablation. This study provides a basis for the clinical study of nsPEFs ablation of liver cancer.

[Determination and Traceability Analysis of Phthalic Acid Esters in Garlic (Allium stivum L.) from Jiangsu Province, China].

Phthalic acid esters (PAEs) are ubiquitous environmental pollutants and are recognized as a threat to the environment and agricultural product safety across the world. In order to investigate the level of PAEs in garlic, soils, and agricultural films from Pizhou City, Jiangsu province, China, 11 garlic samples, 106 soil samples, and 4 agricultural film samples were collected and analyzed using GC-MS. In addition, the uptake and transport characteristics of six PAEs compounds classified as priority pollutants by the United States Environmental Protection Agency (EPA) in the garlic cultivar Daqingke were investigated under hydroponic conditions. The results indicated that dibutyl phthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP) were the dominant PAEs species in garlic cloves of the different garlic varieties from Pizhou City. The average contents of DBP and DEHP in garlic cloves were 0.611 mg·kg-1 and 0.167 mg·kg-1, respectively, which were significantly higher than those of the commercial varieties of garlic. The concentrations of DBP and DEHP differed in three tissues of garlic bulbs, ordered as the skin of garlic bulb>skin of garlic clove>garlic clove. Dimethyl phthalate (DMP), diethyl phthalate (DEP), diisobutyl phthalate (DIBP), DBP, and DEHP were the main PAEs species and were detected in all the surface soils collected from Pizhou City. Compared with the soil allowable concentrations of the six PAEs in the United States, the DMP and DBP concentrations in approximately 100% and 63.2% of soil samples exceeded the recommended allowable concentrations set by the EPA. However, the levels of DEP, DIBP, and DEHP in the soils were below the maximum allowable concentrations set by the EPA. Nevertheless, the average content of DEHP in soils was 486 µg·kg-1 and was found to be much higher than that in the other four PAEs. Six PAEs, including DMP, DEP, DIBP, DBP, butyl benzyl phthalate (BBP), and DEHP, were detected in all the agricultural film samples. Among them, the contents of DBP and DEHP in the agricultural films were the highest, accounting for 53.7%-63.2% of the total PAEs. The amount of PAEs present in the residual film was significantly lower than that in the new film, and all six PAEs were detected in garlic or soil samples, suggesting that agricultural film can be an important source of PAEs in garlic farming soils and garlic. Furthermore, the garlic plants absorbed DMP and DEP efficiently from the substrate and showed higher translocation factors (TFs) for DMP and DEP than those for DBP, BBP, DEHP, and di-n-octyl phthalate (DnOP), resulting in a higher accumulation of DMP and DEP in the over-ground parts of garlic. In contrast, DBP and BBP in roots of garlic displayed higher bioconcentration factors (57.4 and 81.5, respectively) compared to those of the other four PAEs, whereas the TFs of DBP and BBP were lower; this may have contributed to the high accumulation of DBP in garlic bulbs. The BCFs and TFs of DEHP and DnOP in garlic were relatively lower, but the DEHP had been detected in all garlic cloves, which may be a result of the higher DEHP contents in soils.

Is No. 12a Lymph Node Dissection Compliance Necessary in Patients Who Undergo D2 Gastrectomy for Gastric Adenocarcinomas? A Population-Based Retrospective Propensity Score Matching Study.

LN dissection is essential for accurately staging and improving GC patient prognosis. However, the compliance rate for No. 12a LND in practice is low, and its necessity is controversial. Data from GC patients who underwent total gastrectomy (TG)/distal gastrectomy (DG) plus D2 lymphadenectomy between January 2000 and December 2017 at West China Hospital, Sichuan University were reviewed. No. 12a LND noncompliance's effect on the long-term prognosis of patients with GC after D2 gastrectomy was explored. Of the 2788 patients included, No. 12a LND noncompliance occurred in 1753 patients (62.9%). Among 1035 patients with assessable LNs from station 12a, 98 (9.5%) had positive LNs detected at station 12a. No. 12a LN metastasis patients (stage IV not included) had significantly better overall survival (OS) than TNM stage IV patients (p = 0.006). Patients with No. 12a LND compliance had a significantly higher OS than those without, both before (p < 0.001) and after (p < 0.001) PSM. Cox multivariate analysis confirmed that No. 12a LND noncompliance was an independent prognostic factor before (HR 1.323, 95% CI 1.171-1.496, p < 0.001) and after (HR 1.353, 95% CI 1.173-1.560, p < 0.001) PSM. In conclusion, noncompliance with No. 12a LND compromised the long-term survival of patients who underwent D2 gastrectomy for GC.

Mechanism of piR-1245/PIWI-like protein-2 regulating Janus kinase-2/signal transducer and activator of transcription-3/vascular endothelial growth factor signaling pathway in retinal neovascularization.

Inhibiting retinal neovascularization is the optimal strategy for the treatment of retina-related diseases, but there is currently no effective treatment for retinal neovascularization. P-element-induced wimpy testis (PIWI)-interacting RNA (piRNA) is a type of small non-coding RNA implicated in a variety of diseases. In this study, we found that the expression of piR-1245 and the interacting protein PIWIL2 were remarkably increased in human retinal endothelial cells cultured in a hypoxic environment, and cell apoptosis, migration, tube formation and proliferation were remarkably enhanced in these cells. Knocking down piR-1245 inhibited the above phenomena. After intervention by a p-JAK2 activator, piR-1245 decreased the expression of hypoxia inducible factor-1α and vascular endothelial growth factor through the JAK2/STAT3 pathway. For in vivo analysis, 7-day-old newborn mice were raised in 75 ± 2% hyperoxia for 5 days and then piR-1245 in the retina was knocked down. In these mice, the number of newly formed vessels in the retina was decreased, the expressions of inflammation-related proteins were reduced, the number of apoptotic cells in the retina was decreased, the JAK2/STAT3 pathway was inhibited, and the expressions of hypoxia inducible factor-1α and vascular endothelial growth factor were decreased. Injection of the JAK2 inhibitor JAK2/TYK2-IN-1 into the vitreous cavity inhibited retinal neovascularization in mice and reduced expression of hypoxia inducible factor-1α and vascular endothelial growth factor. These findings suggest that piR-1245 activates the JAK2/STAT3 pathway, regulates the expression of hypoxia inducible factor-1α and vascular endothelial growth factor, and promotes retinal neovascularization. Therefore, piR-1245 may be a new therapeutic target for retinal neovascularization.

An improved multi-objective imperialist competitive algorithm for surgical case scheduling problem with switching and preparation times.

Surgical case scheduling is a key issue in the field of medician, which is a challenging work because of the difficulty in assigning resources to patients. This study regards the surgical case scheduling problem as a flexible job shop scheduling problem (FJSP). Considering the switching and preparation time of patients in different stage, an improved multi-objective imperialist competitive algorithm (IMOICA), which adopts the non-dominant sorting method, is proposed to optimize the whole scheduling. First, the social hierarchy strategy is developed to initialize the empire. Then, to enhance the global search ability of the algorithm, the concept of attraction and repulsion (AR) is introduced into the assimilation strategy. Moreover, to increase the diversity of the population, the revolution strategy is utilized. Finally, the variable neighborhood search (VNS) strategy is embedded to improve its exploitation capacity further. Experiments show that scheduling in advance saves time and cost, and IMOICA can solve the surgical case scheduling problem studied efficiently.

Effects of Preoperative Oral Nutritional Supplements on Improving Postoperative Early Enteral Feeding Intolerance and Short-Term Prognosis for Gastric Cancer: A Prospective, Single-Center, Single-Blind, Randomized Controlled Trial.

BACKGROUND: Early enteral nutrition (EN) after abdominal surgery can improve the prognosis of patients. However, the high feeding intolerance (FI) rate is the primary factor impeding postoperative EN. METHODS: Sixty-seven patients who underwent radical subtotal or total gastrectomy for gastric cancer (GC) were randomly allocated to the preoperative oral nutritional supplement group (ONS group) or dietary advice alone (DA group). Both groups were fed via nasojejunal tubes (NJs) from the first day after surgery to the fifth day. The primary endpoint is the FI rate. RESULTS: Of the patients, 66 completed the trial (31 in the ONS group, 35 in the DA group). The FI rate in the ONS group was lower than that in the DA group (25.8% vs. 31.4%, p = 0.249). The postoperative five-day 50% energy compliance rate in the ONS group was higher than that in the DA group (54.8% vs. 48.6%, p = 0.465). The main gastrointestinal intolerance symptoms were distension (ONS vs. DA: 45.2% vs. 62.9, p = 0.150) and abdominal pain (ONS vs. DA: 29.0% vs. 45.7%, p = 0.226). Postoperative nausea/vomiting rate and heartburn/reflux rate were similar between the two groups. We noted no difference in perioperative serum indices, short-term prognosis or postoperative complication rates between the two groups. CONCLUSIONS: The study shows that short-term preoperative ONS cannot significantly improve FI and the energy compliance rate in the early stage after radical gastrectomy.

Assessment of indocyanine green fluorescence lymphography on lymphadenectomy during minimally invasive gastric cancer surgery: a systematic review and meta-analysis.

BACKGROUND: In recent years, indocyanine green fluorescence lymphography has been introduced for lymphatic mapping in gastric cancer surgery. The aim of this study was to investigate the efficacy of ICGFL in lymph node dissection during minimally invasive surgery for gastric cancer. METHODS: A systematic review of electronic databases including PubMed, Embase, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure was performed from the inception to January 2021 for all studies comparing ICGFL with non-ICGFL in GC patients undergoing minimal access gastrectomy. The primary outcome was the total number of harvested lymph nodes. The secondary endpoints were the number of metastatic LNs, operative time, estimated blood loss, and postoperative complications. The registration number of this protocol is PROSPERO CRD42020203443. RESULTS: A total of 13 studies including 1882 participants were included. In this meta-analysis, the use of ICGFL was associated with a higher number of harvested LNs (40.33 vs. 33.40; MD = 6.93; 95%CI: 4.28 to 9.58; P < 0.0001; I2 = 86%). No significant difference was found between the ICGFL and control groups in terms of metastatic LNs (2.63 vs. 2.42; MD = 0.21; 95%CI: -0.46 to 0.87; P = 0.54; I2 = 0%). In addition, the use of ICGFL could be safely performed without increasing the operative time (P = 0.49), estimated blood loss (P = 0.26) and postoperative complications (P = 0.54). CONCLUSION: The use of ICGFL may be a useful tool facilitating complete lymph node dissection during minimally invasive GC resection. However, more high-quality RCTs with large sample size are needed to validate this issue.