Herbacetin Inhibits Asthma Development by Blocking the SGK1/NF-κB Signaling Pathway.

Background: Asthma severely interferes with people's lives through coughing, wheezing and inflammation of the lungs. Herbacetin is a class of natural compounds that inhibit the development of inflammation. However, whether Herbacetin inhibits asthma has not been definitively studied. Methods: Lipopolysaccharides (LPS)-induced lung epithelial (BASE-2B) cells injury model was established, and then the relief of damaged BASE-2B cells with different concentrations of Herbacetin was examined. The cell counting kit (CCK8) was used to detect the effect of Herbacetin on the proliferation ability in ovalbumin (OVA)-induced asthma mice model, and Western Blot and flow cytometry were used to detect the effect of Herbacetin on the apoptosis in OVA-induced asthma mice model. Additionally, pulmonary pathology was detected by HE and Masson staining, and serum inflammatory factors were detected by alveolar lavage fluid. Results: Herbacetin reduces BESA-2B cells induced by LPS level of inflammation, and reactive oxygen species (ROS) generation, inhibits cell apoptosis, promotes cell proliferation, OVA-induced mice lung histopathology test HE staining, serum inflammatory factors show the same results. Western Blot shows that Herbacetin regulates the expression of Caspase-3, Bax, and Bcl-2. SGK1 overexpression increased the rate of apoptosis, and Herbacetin reversed this phenomenon. By silencing the expression of SGK1, it was found that Herbacetin was an inhibitor of SGK1, which could inhibit the NF-κB/p-P65 pathway in asthmatic airway inflammation. Conclusion: Herbacetin reduces pro-inflammatory cytokine levels by inhibiting the SGK1/NF-κB pathway. Our data suggest that Herbacetin has a significant anti-inflammatory effect on asthma and can be used as a potential therapeutic agent.

Long Mu Qing Xin mixture improves behavioral performance in spontaneously hypertensive rats (SHR/NCrl) by upregulating catecholamine neurotransmitters in prefrontal cortex and striatum via DRD1/cAMP/PKA-CREB signaling pathway.

Background: Attention deficit hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder in children, can be effectively alleviated by the herbal preparation Long Mu Qing Xin Mixture (LMQXM), but its mechanism has not been fully elucidated. Objective: To scrutinize the potential pharmacological mechanisms by which LMQXM improves behavior in spontaneously hypertensive rats (SHR/NCrl). Methods: The SHR/NCrl rats were randomly stratified into the model (SHR) group, the methylphenidate hydrochloride (MPH) group, and groups subjected to varying dosages of LMQXM into the medium dose (MD) group with a clinically effective dose, the low dose (LD) group with 0.5 times the clinically effective dose, and high dose (HD) group with 2 times the clinically effective dose. Furthermore, the WKY/NCrl rats constituted the control group. The evaluation of behavior involved the open field test and the Morris water maze test. HPLC, LC-MS, ELISA, immunohistochemistry, Western blot, and RT-qPCR were utilized to scrutinize the catecholamine neurotransmitter content and the expression of proteins and genes associated with the dopamine receptor D1 (DRD1)/cAMP/protein kinase A (PKA)-cAMP response element-binding (CREB) pathway in prefrontal cortex (PFC) and striatum. Results: MPH and LMQXM ameliorated hyperactivity and learning and memory deficits of SHR/NCrl rats. Among them, LMQXM-MD and MPH also upregulated dopamine (DA), norepinephrine (NE), adenylate cyclase (AC) and cAMP levels, and the expression of proteins and genes associated with the DRD1/cAMP/PKA-CREB pathway in PFC and striatum of SHR/NCrl rats. PFC and striatum DA levels were also upregulated in the LMQXM-LD group as well as the striatum DA levels in the LMQXM-HD group, but there were no statistically significant differences in their NE levels compared to the SHR group. LMQXM-LD and LMQXM-HD also upregulated some DRD1/cAMP/PKA-CREB pathway-related proteins and gene expression, but the effects were discernibly disparate in PFC and striatum. Upon comprehensive analysis, LMQXM-MD appeared to be the most effective dose. Conclusion: Our study tentatively suggests that LMQXM may rectify hyperactivity and learning and memory deficits of SHR/NCrl rats by elevating catecholamine neurotransmitters in the PFC and striatum. This effect may be attributed to the potential activation of the DRD1/cAMP/PKA-CREB signaling pathway, which appears to achieve an optimal response at moderate doses.

Significance of Nutritional-Inflammatory Index as Predictors for Total Neoadjuvant Therapy-Induced Tumor Regression in Locally Advanced Rectal Cancer Patients.

Purpose: To evaluate the predictive capacity of the nutritional-inflammatory index and clinicopathological characteristics in patients with locally advanced rectal cancer (LARC) receiving total neoadjuvant therapy (TNT). Methods: Data from 127 patients with LARC receiving TNT from January 2017 to January 2021 were retrospectively analyzed. Clinicopathological characteristics with different TNT-induced responses were compared. The Chi-square test and the Mann-Whitney test were used to analyze the association between pre-TNT factors and TNT-induced responses. Multivariable logistic regression analysis was used to construct a predictive model. Results: In the cohort of 127 patients with LARC who underwent total neoadjuvant therapy (TNT), the mean age was 54.1 ± 11.4 years; 88 (69.3%) were male. Seventy patients (55.1%) exhibited a favorable response to TNT, while 57 patients (44.9%) demonstrated a poor response. Tumor characteristics, including diameter, distance from the anal verge, pre-TNT lymphocyte, pre-TNT hemoglobin, CA199, PLR, and HALP, exhibit correlations with TNT-induced tumor regression. Multivariate logistic regression analysis identified large tumor diameters (> 5.0 cm; p = 0.005, HR 2.958; 95% CI 1.382-6.335) and low HALP (≤ 40; p = 0.002, HR 0.261; 95% CI 0.111-0.612) as predictors of TNT-induced poor responses. Additionally, low levels of HALP were associated with an increased risk of recurrence in patients with LARC with TNT, but this was not statistically significant (p = 0.087, HR 2.008, 95% CI 0.906-4.447). Conclusion: A large tumor diameter and low HALP predict poor tumor regression induced by the CAPOX-based TNT regimen in patients with LARC.

Recent studies have shown that total neoadjuvant therapy (TNT) is becoming a key treatment for some people with advanced rectal cancer. However, there's still a lot we do not know about what affects how well patients respond to this treatment. The aim of this study was to see if certain nutritional and inflammatory measures, along with other clinic characteristics, can predict how well patients with advanced rectal cancer will respond to TNT. We looked back at medical records from 127 patients who received TNT between 2017 and 2021. We examined how certain pre-treatment factors were linked to patients' responses to the therapy. Certain tumor characteristics and blood test results were connected to how well the tumors responded to treatment. Specifically, patients with larger tumors (over 5 cm in diameter) and lower levels of a specific blood marker called HALP were more likely to have a poor response to treatment. Although low HALP was also linked to a higher chance of the cancer coming back, this result was not strong enough to be certain about.

Laparoscopic versus open gastrectomy for nonmetastatic T4a gastric cancer: a meta-analysis of reconstructed individual participant data from propensity score-matched studies.

BACKGROUND: ​The applicability of laparoscopy to nonmetastatic T4a patients with gastric cancer remains unclear due to the lack of high-quality evidence. The purpose of this study was to compare the survival rates of laparoscopic gastrectomy (LG) versus open gastrectomy (OG) for these patients through a meta-analysis of reconstructed individual participant data from propensity score-matched studies. METHODS: PubMed, Embase, Web of Science, Cochrane library and CNKI were examined for relevant studies without language restrictions through July 25, 2023. Individual participant data on overall survival (OS) and disease-free survival (DFS) were extracted from the published Kaplan-Meier survival curves. One-stage and two-stage meta-analyses were performed. In addition, data regarding surgical outcomes and recurrence patterns were also collected, which were meta-analyzed using traditional aggregated data. RESULTS: Six studies comprising 1860 patients were included for analysis. In the one-stage meta-analyses, the results demonstrated that LG was associated with a significantly better DFS (Random-effects model: P = 0.027; Restricted mean survival time [RMST] up to 5 years: P = 0.033) and a comparable OS (Random-effects model: P = 0.135; RMST up to 5 years: P = 0.053) than OG for T4a gastric cancer patients. Two-stage meta-analyses resulted in similar results, with a 13% reduced hazard of cancer-related death (P = 0.04) and 10% reduced hazard of overall mortality (P = 0.11) in the LG group. For secondary outcomes, the pooled results showed an association of LG with less estimated blood loss, faster postoperative recovery and more retrieved lymph nodes. CONCLUSION: Laparoscopic surgery for patients with nonmetastatic T4a disease is associated with a potential survival benefit and improved surgical outcomes.

Prognostic value of the advanced lung cancer inflammation index in patients with gastric cancer after radical gastrectomy: a propensity-score matching cohort study and meta-analysis.

BACKGROUND: Insufficient evidence existed about the prognostic role of the advanced lung cancer inflammation index (ALI) for gastric cancer patients who underwent curative resection. The aim of this study was to identify the predictive ability of ALI for survival after curative gastrectomy. METHODS: We retrospectively analyzed 328 gastric cancer patients who received curative gastrectomy from the database of Chongqing University Cancer Hospital, and investigated the prognostic role of the preoperative ALI compared with clinicopathological variables and other serum biomarkers, such as preoperative neutrophil-to-lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and Lymphocyte-monocyte ratio (LMR). To minimize intergroup differences, propensity score matching (PSM) analysis was employed. Additionally, we performed a meta-analysis of four cohort studies published up to October 2023 following the PRISMA guidelines. RESULTS: In the overall cohort, patients in the low ALI group had a significantly worse overall survival compared to those in the high ALI group (P < 0.0001). Subgroup analysis identified that ALI maintained its prognostic significance across different subgroups. In addition, ROC analysis showed that ALI had a higher AUC value for 3-year overall survival compared to NLR, PLR, and LMR (0.576 vs. 0.573 vs. 0.557 vs. 0.557). Multivariate analysis indicated that ALI, other than other serum biomarkers, was an independent risk factor for decreased overall survival in GC patients following curative surgery (HR = 1.449; 95%CI: 1.028-2.045; P = 0.034). Consistently, PSM analysis supported all of these findings. The meta-analysis including 4 studies evaluating 2542 patients, confirmed the association between the low ALI and poor survival outcomes. CONCLUSION: The preoperative ALI was an independent prognostic factor for survival in gastric cancer patients who underwent curative gastrectomy.

Management of deep sacral and ischial pressure injuries with free-style local perforator flaps: A D+P+DPD model.

BACKGROUND: Previous reports on the treatment of sacral and ischial pressure injuries have not provided clear algorithms for surgical therapies. The objective of this study was to establish a reconstruction algorithm to guide the selection of an ideal free-style perforator flap that can be tailored to the defect in question. METHODS: We used 23 perforator flaps to reconstruct 14 sacral and 8 ischial defects in 22 patients over 5 years. A reconstruction algorithm system was developed based on the anatomical features of the perforator vessels (diameter, D; pulsatility [++∼+++], P) and their position in the skin island (DPD) (ie, D+P+DPD). A perforator-based propeller flap was applied as the first-line choice; if this plan was not feasible, we applied an altered V-Y advancement model or another second-choice technique. RESULTS: All flaps survived, and only 1 patient experienced partial wound dehiscence, which healed by secondary intention. After an average follow-up period of 11.2 months, no patient experienced recurrence or infection. CONCLUSIONS: Free-style perforator flap selection is determined by pressure injury and the desired advantage of a specific approach. The use of free-style perforator-based propeller flaps allows a surgeon to transfer healthy tissue into the defect, shifts the suture line away from the bony prominence, and preserves additional future donor sites. In cases where unexpected variations are encountered, the V-Y advancement model or another technique can be used. The simplified surgical algorithm (D+P+DPD) can provide versatility and reliability, achieve a durable, natural esthetic outcome, and minimize injuries to future donor sites.

A Machine Learning-Based Unenhanced Radiomics Approach to Distinguishing Between Benign and Malignant Breast Lesions Using T2-Weighted and Diffusion-Weighted MRI.

BACKGROUND: Breast MRI has been recommended as supplemental screening tool to mammography and breast ultrasound of breast cancer by international guidelines, but its long examination time and use of contrast material remains concerning. PURPOSE: To develop an unenhanced radiomics model with using non-gadolinium based sequences for detecting breast cancer based on T2-weighted (T2W) and diffusion-weighted (DW) MRI. STUDY TYPE: Retrospective analysis followed by retrospective and prospective cohorts study. POPULATION: 1760 patients: Of these, 1293 for model construction (n = 775 for training and 518 for validation). The remaining patients for model testing in internal retrospective (n = 167), internal prospective (n = 188), and external retrospective (n = 112) cohorts. FIELD STRENGTH/SEQUENCE: 3.0T MR scanners from two institution. T2WI, DWI, and first contrast-enhanced T1-weighted sequence. ASSESSMENT: AUCs in distinguishing breast cancer were compared between combined model with gadolinium agent sequence and unenhanced model. Subsequently, the AUCs in testing cohorts of unenhanced model was compared with two radiologists' diagnosis for this research. Finally, patient subgroup analysis in testing cohorts was performed based on clinical subgroups and different types of malignancies. STATISTICAL TESTS: Mann-Whitney U test, Kruskal-Wallis H test, chi-square test, weighted kappa test, and DeLong's test. RESULTS: The unenhanced radiomics model performed best under Gaussian process (GP) classifiers (AUC: training, 0.893; validation, 0.848) compared to support vector machine (SVM) and logistic, showing favorable prediction in testing cohorts (AUCs, 0.818-0.840). The AUCs for the unenhanced radiomics model were not statistically different in five cohorts from those of the combined radiomics model (P, 0.317-0.816), as well as the two radiologists (P, 0.181-0.918). The unenhanced radiomics model was least successful in identifying ductal carcinoma in situ, whereas did not show statistical significance in other subgroups. DATA CONCLUSION: An unenhanced radiomics model based on T2WI and DWI has comparable diagnostic accuracy to the combined model using the gadolinium agent. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Polydatin alleviates mycoplasma pneumoniae-induced injury via inhibition of Caspase-1/GSDMD-dependent pyroptosis.

Mycoplasma pneumoniae (MP) is one of the main pathogens causing community acquired pneumonia (CAP) in children and adults. Previous pharmacological and clinical studies have shown that Polydatin (PD) exerts anti-inflammatory action by conferring protective benefit in MP pneumonia. However, the mechanism underlying the of PD on MP infection remains unclear. It was found that PD alleviated MP-induced injury by inhibiting caspase-1/gasdermin D (GSDMD)-mediated epithelial pyroptosis. The results demonstrated that PD inhibited the transformation of GSDMD to N-terminal gasdermin-N (GSDMD-N) by decreasing caspase-1 activation, as well as suppressed the formation and secretion of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), reversed Na, K-ATPase reduction, and suppressed LDH release both in vitro and vivo. Taken together, epithelial pyroptosis in BEAS-2B cells and lung injury in mice were prevented by PD. In conclusion, PD suppressed pulmonary injury triggered by MP infection, by inhibiting the caspase-1/GSDMD-mediated epithelial pyroptosis signaling pathway. Thus, PD may be regarded as a potential therapy for MP-induced inflammation.

Comparisons of perioperative and long-term outcomes of laparoscopic versus open gastrectomy for advanced gastric cancer after neoadjuvant therapy: an updated pooled analysis of eighteen studies.

BACKGROUND: Outcomes of laparoscopic surgery in advanced gastric cancer patients who received neoadjuvant therapy represent a controversial issue. We performed an updated meta-analysis to evaluate the perioperative and long-term survival outcomes of laparoscopic gastrectomy (LG) versus conventional open gastrectomy (OG) in this subset of patients. METHODS: Electronic databases including PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure were comprehensively searched up to May 2023. The short-term and long-term outcomes of LG versus OG in advanced gastric cancer patients undergoing neoadjuvant therapy were evaluated. Effect sizes with 95% confidence intervals were always assessed using random-effects model. The prospective protocol was registered with PROSPERO (CRD42022359126). RESULTS: Eighteen studies (2 randomized controlled trials and 16 cohort studies) involving 2096 patients were included. In total, 933 patients were treated with LG and 1163 patients were treated with OG. In perioperative outcomes, LG was associated with less estimated blood loss (MD = - 65.15; P < 0.0001), faster time to flatus (MD = - 0.56; P < 0.0001) and liquid intake (MD = - 0.42; P = 0.02), reduced hospital stay (MD = - 2.26; P < 0.0001), lower overall complication rate (OR = 0.70; P = 0.002) and lower minor complication rate (OR = 0.69; P = 0.006), while longer operative time (MD = 25.98; P < 0.0001). There were no significant differences between the two groups in terms of proximal margin, distal margin, R1/R2 resection rate, retrieved lymph nodes, time to remove gastric tube and drainage tube, major complications and other specific complications. In survival outcomes, LG and OG were not significantly different in overall survival, disease-free survival and recurrence-free survival. CONCLUSION: LG can be a safe and feasible technique for the treatment of advanced gastric cancer patients receiving neoadjuvant therapy. However, more high-quality randomized controlled trials are still needed to further validate the results of our study.

Clinical significance of the advanced lung cancer inflammation index in gastrointestinal cancer patients: a systematic review and meta-analysis.

Background: The advanced lung cancer inflammation index (ALI) has been identified as a scientific and clinical priority in multiple malignancies. The aim of this study is to investigate the value of the ALI before treatment in evaluating postoperative complications (POCs) and survival outcomes in patients with gastrointestinal (GI) cancer. Methods: Electronic databases including PubMed, Embase and Web of Science were comprehensively reviewed up to June 2022. The endpoints were POCs and survival outcomes. Subgroup analyses and sensitivity analyses were also performed. Results: Eleven studies including 4417 participants were included. A significant heterogeneity in the ALI cut-off value among studies was observed. Patients in the low ALI group showed increased incidence of POCs (OR=2.02; 95%CI:1.60-2.57; P<0.001; I2 = 0%). In addition, a low ALI was also significantly associated with worse overall survival (HR=1.96; 95%CI: 1.58-2.43; P<0.001; I2 = 64%), which remained consistent in all subgroups based on country, sample size, tumor site, tumor stage, selection method and Newcastle Ottawa Scale score. Moreover, patients in the low ALI group had an obviously decreased disease-free survival compared to these in the high ALI group (HR=1.47; 95%CI: 1.28-1.68; P<0.001; I2 = 0%). Conclusion: Based on existing evidence, the ALI could act as a valuable predictor of POCs and long-term outcomes in patients with GI cancer. However, the heterogeneity in the ALI cut-off value among studies should be considered when interpreting these findings.

Prophylactic drainage versus non-drainage following gastric cancer surgery: a meta-analysis of randomized controlled trials and observational studies.

BACKGROUND: The role of prophylactic drainage (PD) in gastrectomy for gastric cancer (GC) is not well-established. The purpose of this study is to compare the perioperative outcomes between the PD and non-drainage (ND) in GC patients undergoing gastrectomy. METHODS: A systematic review of electronic databases including PubMed, Embase, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure was performed up to December 2022. All eligible randomized controlled trials (RCTs) and observational studies were included and meta-analyzed separately. The registration number of this protocol is PROSPERO CRD42022371102. RESULTS: Overall, 7 RCTs (783 patients) and 14 observational studies (4359 patients) were ultimately included. Data from RCTs indicated that patients in the ND group had a lower total complications rate (OR = 0.68; 95%CI:0.47-0.98; P = 0.04; I2 = 0%), earlier time to soft diet (MD = - 0.27; 95%CI: - 0.55 to 0.00; P = 0.05; I2 = 0%) and shorter length of hospital stay (MD = - 0.98; 95%CI: - 1.71 to - 0.26; P = 0.007; I2 = 40%). While other outcomes including anastomotic leakage, duodenal stump leakage, pancreatic leakage, intra-abdominal abscess, surgical-site infection, pulmonary infection, need for additional drainage, reoperation rate, readmission rate, and mortality were not significantly different between the two groups. Meta-analyses on observational studies showed good agreement with the pooled results from RCTs, with higher statistical power. CONCLUSION: The present meta-analysis suggests that routine use of PD may not be necessary and even harmful in GC patients following gastrectomy. However, well-designed RCTs with risk-stratified randomization are still needed to validate the results of our study.

Assessing reliability and validity of the Chinese version of the Crown-Crisp Experience Index and its application in pneumoconiosis patients.

In China, among all patients with occupational diseases, 90% have pneumoconiosis. The disease, which leads to psychological problems, seriously affects patients' lives. The Crown-Crisp Experience Index (CCEI) is a multidimensional questionnaire to assess patients' psychological conditions. Yet there is no Chinese version of CCEI. This study, therefore, aims to develop a Chinese CCEI, in line with standard localization procedures, by translating, back-translating, and culturally adapting the original English version. The final Chinese version comprises 47 items in six dimensions. The reliability and validity of the Chinese CCEI were tested by analyzing the data collected from 1,000 pneumoconiosis patients from an occupational disease prevention and treatment hospital. A rank sum test was carried out to compare the phobic anxiety (PHO) between pneumoconiosis patients and retired miners. The results of exploratory factor analysis show six principal components, which explain a total of 78.246% variances. Confirmatory factor analysis shows that the Chi-square freedom ratio (χ2/df) were less than 3, the root mean square error approximation (RMSEA) were less than 0.05, comparative fit Index(CFI) and incremental fit index (IFI) were greater than 0.9, average variance extracted(AVE) in six dimensions were less than 0.5, residual variances(CR) were greater than 0.8, Cronbach's alpha coefficient 0.839, Omega ω coefficient 0.889, and S-CVI 0.88. The PHO of pneumoconiosis patients was significantly higher than that of retired miners exemplified by a statistical difference (P < 0.05). The study shows that the Chinese version of CCEI enjoys a high degree of reliability and validity and thus can be used as a screening tool for measuring patients' anxiety and fear levels.

A modified perforator-based stepladder V-Y advancement flap in the Achilles tendon area for coverage of larger posterior heel defects.

BACKGROUND: Posterior heel defect coverage is challenging because of the paucity of suitable flaps. The traditional local stepladder V-Y advancement flap is recommended only for small defects because of the lack of an axial pedicle. This study reports our experience of using the perforator-based stepladder V-Y advancement flaps in a larger posterior heel defect repair. METHODS: Twenty-two patients with posterior heel defects were treated with modified perforator-based stepladder V-Y advancement flaps in the Achilles tendon area for 11 years. Sixteen males and six females aged 3-74 years underwent surgery. The defect size, perforator characteristics, flap size, flap movement, sural nerve, lesser saphenous vein, deep fascia, flap survival, and outcome quality were analyzed. RESULTS: The perforators were found to predominate within two 2-cm intervals: 0-2 cm and 4-6 cm proximal to the tip of the lateral malleolus. Twenty-one perforator-based flaps healed uneventfully, and only one developed tip necrosis on the lower edge, which healed by secondary intention. The maximum distance of distal movement was 5.0 cm for the modified flap in contrast to 2.5 cm for the traditional flap. All flaps allowed adequate and durable reconstruction to be achieved, with excellent contouring after 2-28 months of follow-up. CONCLUSIONS: The perforator-based stepladder V-Y advancement flap resulted in good outcomes for larger posterior heel defects compared with conventional transfer methods. The flap is a reliable, well-vascularized, sensate, and pliable local flap option that uses similar tissue from adjacent skin for defect repair and creates an internal gliding surface for the Achilles tendon.

Detection of asymptomatic recurrence following curative surgery improves survival in patients with gastric cancer: A systematic review and meta-analysis.

Background: To date, there is no evidence that intensive follow-up provides survival benefit in gastric cancer patients undergoing curative gastrectomy. The aim of this study is to investigate the efficacy of detection of asymptomatic recurrence using intensive surveillance strategy in long-term survival after curative gastric cancer surgery. Methods: A systematic review of electronic databases including PubMed, Embase, Web of Science, the Cochrane Library and China National Knowledge Infrastructure, Clinical Trials Registry and Google Scholar was performed up to April 2022. The primary outcomes were survival outcomes: overall survival, recurrence-free survival and post-recurrence survival. The secondary endpoints were clinicopathological features, recurrence patterns and treatment after recurrence. The registration number of this protocol is PROSPERO CRD42022327370. Results: A total of 11 studies including 1898 participants were included. In the pooled analysis, the detection of asymptomatic recurrence was significantly associated with an improved overall survival compared to patients showing symptoms of recurrence (HR=0.67; 95%CI: 0.57-0.79; P<0.001), which was primarily driven by the prolongation of post-recurrence survival (HR=0.51; 95%CI: 0.42-0.61; P<0.001), since there was no significant difference observed in recurrence-free survival (HR=1.12; 95%CI: 0.81-1.55; P=0.48) between the two groups. Meanwhile, male sex and advanced T stage were more frequently observed in the symptomatic recurrence group. Furthermore, patients in the symptomatic recurrence group had a higher proportion of peritoneal relapse but lower proportion of distant lymph node metastasis. Additionally, patients in the symptomatic recurrence group were less likely to receive surgery treatment and post-recurrence chemotherapy. Conclusion: The detection of asymptomatic recurrence using intensive follow-up was associated with an appreciable improvement in overall survival. However, more robust data from high-quality studies are still required to verify this issue. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=327370, identifier CRD42022327370.

Characterization of Pedestrian Crossing Spatial Violations and Safety Impact Analysis in Advance Right-Turn Lane.

In view of the pedestrian space violation in an advance right-turn lane, the pedestrian crossing paths are divided by collecting the temporal and spatial information of pedestrians and motor vehicles, and the characteristics of different pedestrian crossing behaviors are studied. Combined with the time and speed indicators of conflict severity, the K-means method is used to divide the level of conflict severity. A multivariate ordered logistic regression model of the severity of pedestrian-vehicle conflict was constructed to quantify the effects of different factors on the severity of the pedestrian-vehicle conflict. The study of 1388 pedestrians and the resulting pedestrian-vehicle conflicts found that the type of spatial violation has a significant impact on pedestrian crossing behavior and safety. The average crossing speed and acceleration variation values of spatially violated pedestrians were significantly higher than those of other pedestrians; there is a significant increase in the severity of pedestrian-vehicle conflicts in areas close to the oncoming traffic; the average percentage of pedestrian-vehicle conflicts due to spatial violations increased by 12%, and the percentage of serious conflicts due to each type of spatial violation increased from 18% to 87%, 74%, 30%, and 63%, respectively, compared with those of non-violated pedestrians. In addition, the decrease in the number of lanes and the increase in speed and vehicle reach all lead to an increase in the severity of pedestrian-vehicle conflicts. The results of the study will help traffic authorities to take measures to ensure pedestrian crossing safety.

Inhibitory Effect of Lotus Leaf-Enriched Flavonoid Extract on the Growth of HT-29 Colon Cancer Cells through the Expression of PI3K-Related Molecules.

Objectives: Lotus leaf is rich in flavonoids, and this study is aimed at examining the inhibitory effect of lotus leaf-enriched flavonoid extract (LLEFE) on HT-29 colon cancer cells through phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) expression regulation. Methods: Lotus leaves were extracted by ethanol and purified using FL-3 macroporous resin to create the LLEFE. HT-29 colon cancer cells were tested using various methods: their proliferation was observed by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, their survival status was observed by fluorescence staining, their oxidative stress level was observed by biochemical kits, and their mRNA expression was determined by quantitative polymerase chain reaction (qPCR) assay. Additionally, the composition of the flavonoids in lotus leaf was determined by HPLC. Results: The results showed that the proliferation of NCM460 normal human colon cells was not affected by 0-500 µg/mL LLEFE but the proliferation of HT-29 human colon cancer cells decreased. LLEFE increased the LDH level in an HT-29 colon cancer cell culture medium; also increased the superoxide dismutase (SOD), catalase (CAT) activities, and glutathione (GSH) level in HT-29 cells; and decreased the malondialdehyde (MDA) level. Further experimental results showed that LLEFE upregulated the expression of SOD1, CAT, and GSH mRNA and downregulated the expression of PI3K, Akt, and mammalian target of rapamycin (mTOR) in HT-29 cells. The high-performance liquid chromatography (HPLC) results showed that kaempferin, hyperoside, astragaloside, phloridzin, and quercetin were the main chemical constituents of lotus leaf. Conclusion: Lotus leaves contain functional flavonoids that inhibit the proliferation of HT-29 colon cancer cells and regulate the expression of PI3K/Akt through five important chemicals.

Distinct Metagenomic Signatures in the SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause gastrointestinal symptoms in the patients, but the role of gut microbiota in SARS-CoV-2 infection remains unclear. Thus, in this study, we aim to investigate whether SARS-CoV-2 infection affects the composition and function of gut microbiota. In this study, we demonstrated for the first time that significant shifts in microbiome composition and function were appeared in both SARS-CoV-2-infected asymptomatic and symptomatic cases. The relative abundance of Candidatus_Saccharibacteria was significantly increased, whereas the levels of Fibrobacteres was remarkably reduced in SARS-CoV-2-infected cases. There was one bacterial species, Spirochaetes displayed the difference between patients and asymptomatic cases. On the genus level, Tyzzerella was the key species that remarkably increased in both symptomatic and asymptomatic cases. Analyses of genome annotations further revealed SARS-CoV-2 infection resulted in the significant 'functional dysbiosis' of gut microbiota, including metabolic pathway, regulatory pathway and biosynthesis of secondary metabolites etc. We also identified potential metagenomic markers to discriminate SARS-CoV-2-infected symptomatic and asymptomatic cases from healthy controls. These findings together suggest gut microbiota is of possible etiological and diagnostic importance for SARS-CoV-2 infection.

Antioxidative and Anti-Inflammatory Effects of Lactobacillus plantarum ZS62 on Alcohol-Induced Subacute Hepatic Damage.

Lactobacillus plantarum ZS62 is a newly isolated strain from naturally fermented yogurt that might offer some beneficial effects in the setting of alcohol-induced subacute liver injury. The liver-protective effect of L. plantarum ZS62 was investigated by gavage feeding of mice with this Lactobacillus strain (1 × 109 CFU/kg BW) before alcohol administration daily for 7 days. We then compared hepatic morphology, liver function indexes, liver lipid levels, inflammation, oxidative stress levels, and mRNA expression of oxidative metabolism- and inflammation-related genes in mice that had been pretreated with Lactobacillus plantarum versus control mice that had not been pretreated. Our results showed that L. plantarum ZS62 attenuated alcohol-induced weight loss; prevented morphological changes in hepatocytes; reduced markers of liver damage including aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), hyaluronidase (HAase), precollagen III (PC III), and inflammatory cytokines; and enhanced the antioxidative status. L. plantarum ZS62 also significantly downregulated inflammation-related genes and upregulated lipid- and oxidative-metabolism genes. Thus, Lactobacillus plantarum pretreatment appears to confer hepatic protection by reducing inflammation and enhancing antioxidative capacity. The protective effect of L. plantarum ZS62 was even better than that of a commonly used commercial lactic acid bacteria (Lactobacillus delbrueckii subsp. Bulgaricus). The L. plantarum ZS62 might be a potentially beneficial prophylactic treatment for people who frequently drink alcoholic beverages.

The Preventive Effect of Lactobacillus plantarum ZS62 on DSS-Induced IBD by Regulating Oxidative Stress and the Immune Response.

In this study, we used DSS to establish an IBD mouse model to study the preventive effect of Lactobacillus plantarum (L. plantarum) ZS62 on IBD in the context of oxidative stress and the immune response. We assessed the mitigating effect of this strain on IBD mice by examining the length of and histopathological changes in the colon, determining the serum antioxidant index and the levels of inflammatory cytokines, as well as the mRNA and protein expression levels of relevant genes. The study results showed that L. plantarum ZS62 could inhibit colonic atrophy in IBD mice, reduce the degree of colonic damage, downregulate the serum levels of MDA, MPO, IL-1ß, IL-6, IL-12, TNF-α, and IFN-γ and the relative mRNA and protein expression of IL-1ß, IL-12, TNF-α, COX-2, iNOS, and NF-κB p65 in mouse colon tissues, and upregulate the serum levels of CAT, T-SOD, and IL-10 and the relative mRNA and protein expression of Cu/Zn SOD, Mn SOD, GSH-Px, CAT, IL-10, and IκB-α in colon tissues. In summary, L. plantarum ZS62 exhibited a good preventive effect on DSS-induced IBD by regulating oxidative stress and the immune response.