Thalidomide for Recurrent Bleeding Due to Small-Intestinal Angiodysplasia.

BACKGROUND: Recurrent bleeding from the small intestine accounts for 5 to 10% of cases of gastrointestinal bleeding and remains a therapeutic challenge. Thalidomide has been evaluated for the treatment of recurrent bleeding due to small-intestinal angiodysplasia (SIA), but confirmatory trials are lacking. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial to investigate the efficacy and safety of thalidomide for the treatment of recurrent bleeding due to SIA. Eligible patients with recurrent bleeding (at least four episodes of bleeding during the previous year) due to SIA were randomly assigned to receive thalidomide at an oral daily dose of 100 mg or 50 mg or placebo for 4 months. Patients were followed for at least 1 year after the end of the 4-month treatment period. The primary end point was effective response, which was defined as a reduction of at least 50% in the number of bleeding episodes that occurred during the year after the end of thalidomide treatment as compared with the number that occurred during the year before treatment. Key secondary end points were cessation of bleeding without rebleeding, blood transfusion, hospitalization because of bleeding, duration of bleeding, and hemoglobin levels. RESULTS: Overall, 150 patients underwent randomization: 51 to the 100-mg thalidomide group, 49 to the 50-mg thalidomide group, and 50 to the placebo group. The percentages of patients with an effective response in the 100-mg thalidomide group, 50-mg thalidomide group, and placebo group were 68.6%, 51.0%, and 16.0%, respectively (P<0.001 for simultaneous comparison across the three groups). The results of the analyses of the secondary end points supported those of the primary end point. Adverse events were more common in the thalidomide groups than in the placebo group overall; specific events included constipation, somnolence, limb numbness, peripheral edema, dizziness, and elevated liver-enzyme levels. CONCLUSIONS: In this placebo-controlled trial, treatment with thalidomide resulted in a reduction in bleeding in patients with recurrent bleeding due to SIA. (Funded by the National Natural Science Foundation of China and the Shanghai Municipal Education Commission, Gaofeng Clinical Medicine; ClinicalTrials.gov number, NCT02707484.).

The significance of serum SLC7A11 levels in the occurrence of vascular calcification in maintenance peritoneal dialysis patients.

AIM: This research aimed to explore the serum levels of solute carrier family 7 member 11 (SLC7A11) in patients with maintenance peritoneal dialysis (MPD) and its correlation with vascular calcification (VC) and clinical results. METHODS: This present prospective observational cohort study enrolled 189 patients with MPD who were undergoing regular peritoneal dialysis for over 3 months in our hospital from February 2020 to July 2022. The abdominal aortic calcification score was used to assess the VC condition of MPD patients. The serum SLC7A11, interleukin (IL)-6, IL-1ß and C-reactive protein levels were measured by enzyme-linked immunosorbent assay (ELISA). Demographic and clinical statistics were collected. All patients were followed up for 1 year and the overall survival time (OS) of all patients were recorded. All data used SPSS 18.0 for statistical analyses. RESULTS: Patients with moderate/severe calcification in MPD had a longer duration of dialysis, higher serum levels of phosphate (P) and calcium (Ca) and lower serum levels of SLC7A11. Spearman's analysis revealed a negative correlation between serum SLC7A11 levels and the levels of P, Ca and IL-1ß. Additionally, we observed an association between serum SLC7A11 levels and clinical prognosis as well as the extent of VC in MPD patients. Multivariate logistic regression analysis indicated that dialysis duration, SLC7A11, and P were risk factors for VC in MPD patients. CONCLUSION: The serum SLC7A11 levels decreased remarkably in MPD patients with moderate/severe calcification. This study may provide new targets and comprehensive approach to cardiovascular protection in patients with chronic kidney disease.

Arthroscopic inferior leaf meniscectomy of the involved anterior horn in the lateral meniscus horizontal tear via an accessary extreme far anteromedial portal.

BACKGROUND: An accessory extreme far anteromedial portal can improve visualisation and ease inferior leaf meniscectomy in patients with lateral meniscal anterior horn horizontal tears. However, the therapeutic outcomes of adding an accessory extreme far anteromedial portal remain unclear. This study aimed to evaluate the clinical efficacy of adding an accessory extreme far anteromedial portal for treating lateral meniscal horizontal tears involving the anterior horns. METHODS: This retrospective study included 101 patients with anterior horn involvement in lateral meniscal horizontal tears who underwent arthroscopic unstable inferior leaf meniscectomy between January 2016 and December 2020. The pathologies were diagnosed using physical examinations and magnetic resonance imaging. The anterior horn involved in the lateral meniscal horizontal tears was treated using inferior leaf meniscectomy. The primary endpoints were changes in the visual analogue scale, Lysholm, International Knee Documentation Committee, and Tegner scores at the final follow-up. The secondary endpoint was meniscal cure rate at 3 months postoperatively. The preoperative and postoperative functional scores were compared. The occurrence of complications was recorded. RESULTS: All patients were followed up for an average of 4.9 ± 1.2 years (range 2.3-7.5 years). After 4 months, none of the patients experienced pain, weakness, instability, or tenderness in the lateral joint line, achieving an imaging cure rate of 98%. At the final follow-up, significant postoperative improvements were observed in the average values of the visual analogue scale score (3.5 ± 0.7 vs. 0.7 ± 0.6), Lysholm score (62.7 ± 4.4 vs. 91.8 ± 3.1), International Knee Documentation Committee score (61.9 ± 3.7 vs. 91.7 ± 9.5), and Tegner score (2.0 ± 0.7 vs. 6.1 ± 0.7). Excellent Lysholm scores were obtained in 81 patients, and good outcomes were obtained in 18 patients, with an excellent-to-good rate of 98.0%. CONCLUSIONS: Inferior leaf resection via the accessory far anteromedial portal is a safe treatment option for the involved anterior horn in lateral meniscal horizontal tears. This approach enhances visibility and facilitates surgical procedures, with minimal complications.

Clinical outcomes following direct anterior approach during total hip arthroplasty without hip extension: a retrospective comparative study.

BACKGROUND: Traditional total hip arthroplasty (THA) using the direct anterior approach (DAA) requires a hip extension. This study aimed to compare the clinical outcomes of patients undergoing THA with DAA using either the no hip extension (NHE) or the traditional hip extension (THE) strategy. METHODS: A retrospective analysis of demographics, clinical and radiological outcomes, and occurrence of complications was performed using data from 123 patients treated between January 2020 and November 2021. The patients were categorised into two groups: NHE (84 patients) and THE (39 patients). RESULTS: The NHE group exhibited shorter operative time and had more male participants with higher ages. Comparable outcomes were observed in the visual analogue scale, Harris Hip, and Oxford Hip scores at the final follow-up. Furthermore, complications were observed in the NHE and THE groups, including two and one greater trochanteric fractures and three and one transfusions, respectively. CONCLUSIONS: Compared to the THE, employing the NHE strategy during THA with DAA in elderly and young female patients resulted in comparable clinical outcomes with several advantages, such as favourable surgical time. The NHE method also exhibited good safety and effectiveness. Therefore, the NHE strategy may be a favourable option for elderly and young female patients.

Enhancing the Quality of Low-Alcohol Navel Orange Wine through Simultaneous Co-Fermentation Using Saccharomyces cerevisiae SC-125, Angel Yeast SY, and Lactiplantibacillus plantarum BC114.

To date, there has been limited research on the interactive effects of yeast and lactic acid bacteria (LAB) on the sensory qualities of navel orange wine. In this study, using Jintang navel orange juice as the raw material, multi-microbial fermentation was conducted with Saccharomyces cerevisiae SC-125 and Angel yeast SY, as well as Lactiplantibacillus plantarum BC114. Single yeast and co-fermentation with Lactiplantibacillus plantarum were used as the control groups. The research aimed to investigate the physicochemical parameters of navel orange wine during fermentation. Additionally, headspace solid-phase microextraction gas chromatography-mass spectrometry (HP-SPME-GC-MS) was employed to determine and analyze the types and levels of flavor compounds in the navel orange wines produced through the different fermentation methods. The co-fermentation using the three strains significantly enhanced both the quantity and variety of volatile compounds in the navel orange wine, concomitant with heightened total phenol and flavonoid levels. Furthermore, a notable improvement was observed in the free radical scavenging activity. A sensory evaluation was carried out to analyze the differences among the various navel orange wines, shedding light on the impact of different wine yeasts and co-fermentation with LAB on the quality of navel orange wines.

The construction of Moringa oleifera seed protein emulsion: in vitro digestibility and delivery of ß-carotene.

BACKGROUND: ß-Carotene (BC) is difficult to apply effectively in the food industry due to its low solubility and bioavailability. This work aimed to fabricate Moringa oleifera seed protein (MOSP) stabilized emulsions as delivery vehicles for BC and investigate the effect of aqueous phase conditions including pH and ionic strength on this system. RESULTS: All MOSP samples were positively charged and the particle size of MOSP increased with the increase of pH. At pH 5.0 and 0.2 mol L-1 sodium chloride (NaCl), the MOSP emulsion demonstrated the highest stability coefficient and minimal creaming index, while exhibiting a lower release rate in vitro digestion. The rheological behavior of all MOSP emulsions within the frequency range of 0.1-10 Hz was dominated by viscoelasticity, forming an elastic network structure through dispersed droplets. Additionally, the MOSP emulsion loaded with BC prepared at pH 5.0 and 0.2 mol L-1 NaCl displayed enhanced ultraviolet light stability (52.31 ± 0.03% and 51.86 ± 0.05%) as well as thermal stability (72.39 ± 8.67% and 86.78 ± 10.69%). Furthermore, the BC in the emulsion at pH 7.0 exhibited favorable stability (65.14 ± 0.02%) and optimal bioaccessibility (40.30 ± 0.04%) in vitro digestion. CONCLUSION: The results provided reference data for utilizing MOSP as a novel emulsifier and broadening the application of BC in the food industry. © 2024 Society of Chemical Industry.

KRASG12C mutation-induced TOPK overexpression contributes to tumour progression in non-small cell lung cancer.

KRAS mutation is the most frequent type of genetic mutation in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma. However, KRAS mutation can affect many biological processes and the mechanisms underlying KRAS mutation-mediate carcinogenesis in NSCLC have not been fully understood. In this research, we found that KRASG12C mutation was associated with the upregulation of T-LAK cell-originated protein kinase (TOPK), which is a well-known serine/threonine MAPK-like protein kinase implicated in tumorigenesis. The overexpression of TOPK significantly promoted the malignant phenotype of A549 cells, and TOPK silencing impaired the malignant phenotype with KRASG12C mutation. Moreover, we demonstrated that TOPK level was regulated by MAPK/ERK signalling and the transcription factor Elk1. TOPK was also found to promote the activation of NF-κB signalling in A549 cells with KRASG12C mutation via facilitating the phosphorylation of TAK1. In the in vivo tumorigenesis model, the administration of TOPK inhibitor OTS514 enhanced the anticancer effect of 5-FU, and the combinatory use of OTS514 and KRASG12C inhibitor AMG510 showed synergistic anti-tumour effect. These results suggest that KRAS-TOPK axis contributes to the progression of NSCLC and targeting this axis could synergize with anticancer effect of the existing chemotherapeutics.

Metformin abrogates Fusobacterium nucleatum-induced chemoresistance in colorectal cancer by inhibiting miR-361-5p/sonic hedgehog signaling-regulated stemness.

BACKGROUND: Chemotherapy resistance is the major cause of recurrence in patients with colorectal cancer (CRC). A previous study found that Fusobacterium (F.) nucleatum promoted CRC chemoresistance. Additionally, metformin rescued F. nucleatum-induced tumorigenicity of CRC. Here, we aimed to investigate whether metformin could revert F. nucleatum-induced chemoresistance and explore the mechanism. METHODS: The role of metformin in F. nucleatum-infected CRC cells was confirmed using cell counting kit 8 assays and CRC xenograft mice. Stemness was identified by tumorsphere formation. Bioinformatic analyses were used to explore the regulatory molecules involved in metformin and F. nucleatum-mediated regulation of the sonic hedgehog pathway. RESULTS: We found that metformin abrogated F. nucleatum-promoted CRC resistance to chemotherapy. Furthermore, metformin attenuated F. nucleatum-stimulated stemness by inhibiting sonic hedgehog signaling. Mechanistically, metformin diminished sonic hedgehog signaling proteins by targeting the MYC/miR-361-5p cascade to reverse F. nucleatum-induced stemness, thereby rescuing F. nucleatum-triggered chemoresistance in CRC. CONCLUSIONS: Metformin acts on F. nucleatum-infected CRC via the MYC/miR-361-5p/sonic hedgehog pathway cascade, subsequently reversing stemness and abolishing F. nucleatum-triggered chemoresistance. Our results identified metformin intervention as a potential clinical treatment for patients with chemoresistant CRC with high amounts of F. nucleatum.

The effect of posterior cruciate ligament tibial avulsion fracture on functional outcomes in knees with concomitant ipsilateral lower limb fractures: a matched-cohort analysis.

BACKGROUND: At present, the optimal treatment for posterior cruciate ligament tibial avulsion fracture (PCLTAF) combined with concomitant ipsilateral lower limb fractures remains unclear. The present study aimed to assess the preliminary outcomes of treatment for PCLTAF with concomitant ipsilateral lower limb fractures by open reduction and internal fixation (ORIF). MATERIALS AND METHODS: The medical records of patients who sustained PCLTAF with concomitant ipsilateral lower limb fractures between March 2015 and February 2019 and underwent treatment at a single institution were retrospectively reviewed. Imaging examinations performed at the time of injury were applied to identify concomitant ipsilateral lower limb fractures. We used 1:2 matching between patients with PCLTAF combined with concomitant ipsilateral lower limb fractures (combined group; n = 11) and those with isolated PCLTAF (isolated group; n = 22). Outcome data were collected, including the range of motion (ROM) and visual analogue scale (VAS), Tegner, Lysholm, and International Knee Documentation Committee (IKDC) scores. At the final follow-up, the clinical outcomes were compared between the combined and isolated groups and between patients who underwent early-stage surgery and those who underwent delayed treatment for PCLTAF. RESULTS: Thirty-three patients (26 males, 7 females) were included in this study, with eleven patients having PCLTAF and concomitant ipsilateral lower limb fractures and a follow-up of 3.1 to 7.4 years (average, 4.8 years). Compared to patients in the isolated group, patients in the combined group demonstrated significantly worse Lysholm scores (85.7 ± 5.8 vs. 91.5 ± 3.9, p = 0.040), Tegner scores (4.4 ± 0.9 vs. 5.4 ± 0.8, p = 0.006), and IKDC scores (83.6 ± 9.3 vs. 90.5 ± 3.0, p = 0.008). Inferior outcomes were found in patients with delayed treatment. CONCLUSIONS: Inferior results were found in patients with concomitant ipsilateral lower limb fractures, while better outcomes were obtained in patients with PCLTAF through early-stage ORIF using the posteromedial approach. The present findings may help determine the prognoses of patients with PCLTAF combined with concomitant ipsilateral lower limb fractures treated through early-stage ORIF.

Hip effusion/synovitis influences results after multiple drilling core decompression for bone marrow edema syndrome of hip.

BACKGROUND: At present, it is not known whether hip effusion/synovitis affects the therapeutic effect of multiple drilling core decompression (MDCD) in patients with bone marrow edema syndrome of hip (BMESH). The aims were to assess hip effusion/synovitis and its relationship with results of MDCD in patients with BMESH. METHODS: The data of undergoing arthroscopic-assisted MDCD for treatment of BMESH with hip effusion/synovitis by one surgeon were retrospectively reviewed from the associated medical records at the Affiliated Hospital of Zunyi Medical University (2016-2019). Seven patients (9 hips) participated in this study. Patients were followed up at 1, 2, 3, 6, 12 and 24 months. Data included demographics and clinical outcomes. The pre- and postoperative pain and functional outcomes were measured with the visual analogue scale (VAS), Harris Hip Score (HHS), Hip Outcome Score Activities of Daily Living subscale (HOS-ADL), International Hip Outcome Tool-12 (iHOT-12) and range of motion (ROM). RESULTS: Seven patients (9 hips) were followed up. Disappearance of hip pain immediately obtained at rest after surgery. All of 7 patients returned to their former activity level at postoperative 3 months, bone marrow edema had disappeared on Magnetic Resonance Imaging (MRI). The VAS, HHS, HOS-ADL, iHOT-12, and ROM at postoperative 1 month had a significant difference (P < 0.05) compared with preoperative. It was also statistically significant (P < 0.05) when compared with other time points. At the final follow-up, all patients had no limited ROM, which was symmetrical with the contralateral of hip joint. Hip effusion/synovitis were observed in 9 hips. Labral tears, cartilage fissure, and loose bodies were observed in 1 hip, respectively. Kirschner wire tracks bleeding occurred in 1 hip. No other complications occurred. CONCLUSIONS: Hip effusion/synovitis could affect the clinical outcomes after MDCD in patients with BMESH. Arthroscopic procedure of hip effusion/synovitis can shorten postoperative pain relief time, disappearance time of bone marrow edema on MRI. It can simultaneously diagnose and treat other concomitant intraarticular pathologies, and be a safe operation with fewer complications.

Whey protein hydrolysates as prebiotic and protective agent regulate growth and survival of Lactobacillus rhamnosus CICC22152 during spray/freeze-drying, storage and gastrointestinal digestion.

BACKGROUND: Probiotic products are receiving increasing attention because of their tremendous beneficial health effects. However, it is still a great challenge to preserve probiotic viability during processing, storage and gastrointestinal digestion. Encapsulation is a widely known technology for enhancing bacterial viability and product stability. Hence highly hydrolyzed whey protein hydrolysate (HWPH) and moderately hydrolyzed whey protein hydrolysate (MWPH) used as a one-step culture medium and wall material for Lactobacillus rhamnosus were investigated. RESULTS: H/MWPH-substitutive medium for the growth of Lactobacillus rhamnosus presented double the biomass production compared to other media. The H/MWPH-substitutive medium in combination with freeze drying also led to the highest survival ratio (97.13 ± 9.16%) and cell viability (10.62 log CFU g-1 ). The highest survival rate of spray-dried cells was 85.56 ± 7.4%. In addition, the cell viability of spray-dried Lactobacillus rhamnosus with MWPH as culture and dry medium was 0.79 log CFU g-1 higher than that of HWPH. Images confirmed that spray-dried Lactobacillus rhamnosus in MWPH provided better protection and it showed greater sustained viability after gastrointestinal digestion. CONCLUSION: Overall, WPH just as carrier provides better thermal protection and MWPH is a preferable two-in-one medium for probiotics. © 2022 Society of Chemical Industry.

Analysis of the Development Trend in Forensic Odontology Based on CiteSpace.

OBJECTIVES: To realize the dynamic visualization of forensic odontology based on the bibliometrics methods, and capture the research hotspots and identify the future development trend. METHODS: Literature articles published from January 1995 to December 2020 were searched according to specific subject words in the core data set of Web of Science. The visualization analysis of publishing country, institution, discipline, author, co-cited journal and keywords was performed by CiteSpace 5.7.R5W software. RESULTS: The annual analysis of publications showed an upward trend of forensic odontology research literature year by year, with the number of annual publications more than 110 in the last five years. Developed countries were the main source of contributions and the average centrality was greater than 0.2. The research of forensic odontology involved multiple disciplines, including stomatology, biology, computer science and medical imaging, with a distinct interdisciplinary feature. A total of 115 nodes were obtained by keyword cluster analysis. The principal line of forensic odontology mainly included individual identification and age estimation and the emergence of hotspots was closely related to new technologies. Population-based odontology investigation, improvement of traditional dental age estimation method and dental age estimation based on new technology were popular research in forensic odontology. CONCLUSIONS: Developing countries urgently need to increase the focus on related research. It may be an important direction for the development of forensic odontology to establish and enrich the regional dental database, develop new odontology identification technology combined with frontier and high-end technology, and develop the identification program based on advanced information technology.

Lack of Knowledge, the main Stumbling Block of Fertility Preservation Promotion in China.

The aim of this study is to evaluate fertility preservation (FP) popularization in China among female cancer patients in terms of awareness of fertility, knowledge about FP, and attitudes toward FP. A questionnaire-based survey was conducted among female cancer patients in Tongji Hospital in China from March 2019 to July 2019. The 29 fertility-related issues, which were presented in either five-point Likert scales or "yes or no", in this questionnaire consisted of demographic characteristic and disease-related situation, awareness of fertility, knowledge about FP, and attitudes toward FP. Participants were required to finish the questionnaire, and data were gathered and analyzed by SPSS. Forty-five valid questionnaires without missing data remained in the final analysis. The survey discovered that a regional imbalanced limitation in knowledge of infertility risk and FP in young cancer patients acted as a major obstacle in FP promotion nationwide and FP decision-making in patients. Compared with rural patients, patients from urban areas were more eager to give birth and more likely to have a better understanding of FP with a more positive attitude. Moreover, most of the participants (62.2%) had a low level of understanding of FP, although they remained positive toward it. "Cancer treatment as the priority", "Cancer relapse caused by FP", and "Health of the next generation" were the top three factors affecting decisions on FP. The findings revealed a general FP actuality in China and specifically offered some intervention targets in the near future to improve FP service and networks, benefiting more female patients of childbearing age who are at risk of infertility.

A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice.

OBJECTIVE: This study aimed to develop a novel therapeutic vaccine based on a unique B cell epitope and investigate its therapeutic potential against chronic hepatitis B (CHB) in animal models. METHODS: A series of peptides and carrier proteins were evaluated in HBV-tolerant mice to obtain an optimised therapeutic molecule. The immunogenicity, therapeutic efficacy and mechanism of the candidate were investigated systematically. RESULTS: Among the HBsAg-aa119-125-containing peptides evaluated in this study, HBsAg-aa113-135 (SEQ13) exhibited the most striking therapeutic effects. A novel immunoenhanced virus-like particle carrier (CR-T3) derived from the roundleaf bat HBV core antigen (RBHBcAg) was created and used to display SEQ13, forming candidate molecule CR-T3-SEQ13. Multiple copies of SEQ13 displayed on the surface of this particulate antigen promote the induction of a potent anti-HBs antibody response in mice, rabbits and cynomolgus monkeys. Sera and purified polyclonal IgG from the immunised animals neutralised HBV infection in vitro and mediated efficient HBV/hepatitis B virus surface antigen (HBsAg) clearance in the mice. CR-T3-SEQ13-based vaccination induced long-term suppression of HBsAg and HBV DNA in HBV transgenic mice and eradicated the virus completely in hydrodynamic-based HBV carrier mice. The suppressive effects on HBsAg were strongly correlated with the anti-HBs level after vaccination, suggesting that the main mechanism of CR-T3-SEQ13 vaccination therapy was the induction of a SEQ13-specific antibody response that mediated HBV/HBsAg clearance. CONCLUSIONS: The novel particulate protein CR-T3-SEQ13 suppressed HBsAg effectively through induction of a humoural immune response in HBV-tolerant mice. This B cell epitope-based therapeutic vaccine may provide a novel immunotherapeutic agent against chronic HBV infection in humans.

SRSF3 functions as an oncogene in colorectal cancer by regulating the expression of ArhGAP30.

BACKGROUND: Splicing factor SRSF3 is an oncogene and overexpressed in various kinds of cancers, however, the function and mechanism involved in colorectal cancer (CRC) remained unclear. The aim of this study was to explore the relationship between SRSF3 and carcinogenesis and progression of CRC. METHODS: The expression of SRSF3 in CRC tissues was detected by immunohistochemistry. The proliferation and invasion rate was analyzed by CCK-8 assay, colony formation assay, transwell invasion assay and xenograft experiment. The expression of selected genes was detected by western blot or real time PCR. RESULTS: SRSF3 is overexpressed in CRC tissues and its high expression was associated with CRC differentiation, lymph node invasion and AJCC stage. Upregulation of SRSF3 was also associated with shorter overall survival. Knockdown of SRSF3 in CRC cells activated ArhGAP30/Ace-p53 and decreased cell proliferation, migration and survival; while ectopic expression of SRSF3 attenuated ArhGAP30/Ace-p53 and increases cell proliferation, migration and survival. Targeting SRSF3 in xenograft tumors suppressed tumor progression in vivo. CONCLUSIONS: Taken together, our data identify SRSF3 as a regulator for ArhGAP30/Ace-p53 in CRC, and highlight potential prognostic and therapeutic significance of SRSF3 in CRC.

PD-L1 Overexpression on Tumor-Infiltrating Lymphocytes Related to Better Prognosis of Colorectal Cancer.

BACKGROUND: PD-L1 expression on tumor-infiltrating lymphocytes (TILs) has recently been reported as a biomarker for colorectal cancer (CRC). However, the prognostic and clinical significance of PD-L1 on TILs in CRC remains controversial. We performed this meta-analysis to evaluate the association between the PD-L1 expression on TILs and clinicopathological features and prognosis of CRC patients. METHODS: A comprehensive literature search for relevant studies published up to Feb 2020 was performed using Medline, Embase, and Web of Science. Odds ratio (OR) with 95% CI was selected to appraise the correlation between PD-L1 expression on TILs with prognostic and clinicopathological characteristics of CRC patients. Begg's and Egger's test were used to assess publication bias. The statistical analysis was conducted using Stata software. RESULTS: A total of 19 studies including 5,213 CRC cases were included in this meta-analysis. The pooled results showed that PD-L1 overexpression on TILs was relevant to longer OS (OR = 1.36, 95% CI = 1.19 - 1.55, p < 0.01) and longer DFS/RFS (OR = 1.22, 95% CI = 1.03 - 1.44, p = 0.02). Moreover, CRC patients with high expression of PD-L1 on TILS was associated with lower T stage (OR = 2.30, 95% CI = 1.85 - 2.87, p < 0.01), less lymph node in-vasion (OR = 1.48, 95% CI = 1.03 - 2.13, p = 0.03), less distant metastasis (OR = 2.56, 95% CI = 1.81 - 3.64, p < 0.01), earlier TNM stage (OR = 1.93, 95% CI = 1.34 - 2.66, p < 0.01), later tumor grade (OR = 0.38, 95% CI = 0.23 - 0.62, p < 0.01) and high MSI status (OR = 0.36, 95% CI = 0.25 - 0.52, p < 0.01). But it is not related to tumor size, tumor differentiation, MMR status, BRAF mutant, and KRAS mutant. CONCLUSIONS: This meta-analysis revealed that PD-L1 expression on TILs can serve as a significant biomarker for positive prognosis and clinicopathological features of CRC. Our results may provide some useful information when using PD-L1 expression to predict the survival of CRC patients and to select the beneficial CRC patients from PD-1/PD-L1 antibody treatment.

Improving the diagnosis of common parotid tumors via the combination of CT image biomarkers and clinical parameters.

BACKGROUND: Our study aims to develop and validate diagnostic models of the common parotid tumors based on whole-volume CT textural image biomarkers (IBMs) in combination with clinical parameters at a single institution. METHODS: The study cohort was composed of 51 pleomorphic adenoma (PA) patients and 42 Warthin tumor (WT) patients. Clinical parameters and conventional image features were scored retrospectively and textural IBMs were extracted from CT images of arterial phase. Independent-samples t test or Chi-square test was used for evaluating the significance of the difference among clinical parameters, conventional CT image features, and textural IBMs. The diagnostic performance of univariate model and multivariate model was evaluated via receiver operating characteristic (ROC) curve and area under ROC curve (AUC). RESULTS: Significant differences were found in clinical parameters (age, gender, disease duration, smoking), conventional image features (site, maximum diameter, time-density curve, peripheral vessels sign) and textural IBMs (mean, uniformity, energy, entropy) between PA group and WT group (P<0.05). ROC analysis showed that clinical parameter (age) and quantitative textural IBMs (mean, energy, entropy) were able to categorize the patients into PA group and WT group, with the AUC of 0.784, 0.902, 0.910, 0.805, respectively. When IBMs were added in clinical model, the multivariate models including age-mean and age-energy performed significantly better than the univariate models with the improved AUC of 0.940, 0.944, respectively (P<0.001). CONCLUSIONS: Both clinical parameter and CT textural IBMs can be used for the preoperative, noninvasive diagnosis of parotid PA and WT. The diagnostic performance of textural IBM model was obviously better than that of clinical model and conventional image model in this study. While the multivariate model consisted of clinical parameter and textural IBM had the optimal diagnostic performance, which would contribute to the better selection of individualized surgery program.

[Clinical effectiveness of Subjective Global Nutritional Assessment in hospitalized children with cerebral palsy].

OBJECTIVE: To investigate the nutritional status of children with cerebral palsy (CP) and the clinical effectiveness of Subjective Global Nutritional Assessment (SGNA) in nutritional assessment of hospitalized children with CP. METHODS: A total of 208 children with CP, aged 1-5 years, who were hospitalized from April to October 2019 were enrolled as subjects. SGNA was used to investigate nutritional status, and the Z-score method recommended by the World Health Organization was used as a reference standard to validate the clinical effectiveness of SGNA. RESULTS: The detection rate of malnutrition in children with CP was 42.3% by SGNA and 39.4% by the Z-score method (P>0.05). The application of SGNA showed high consistency between different evaluators (κ=0.621, P<0.001). With the Z-score method as the reference standard, SGNA had a sensitivity of 80.5%, a specificity of 82.5%, a positive predictive value of 75.0%, and a negative predictive value of 86.7%, and high consistency was observed between the two evaluation methods (κ=0.622, P<0.001). SGNA was moderately consistent with weight-for-age Z-score and height-for-age Z-score (κ=0.495 and 0.478 respectively, P<0.001) and was poorly consistent with weight-for-height Z-score (κ=0.197, P<0.05). CONCLUSIONS: There is a relatively high incidence rate of malnutrition in children with CP. SGNA can be used as a tool to assess the nutritional status of children with CP.

Developing TRAIL/TRAIL death receptor-based cancer therapies.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that can initiate the apoptosis pathway by binding to its associated death receptors DR4 and DR5. The activation of the TRAIL pathway in inducing tumor-selective apoptosis leads to the development of TRAIL-based cancer therapies, which include recombinant forms of TRAIL, TRAIL receptor agonists, and other therapeutic agents. Importantly, TRAIL, DR4, and DR5 can all be induced by synthetic and natural agents that activate the TRAIL apoptosis pathway in cancer cells. Thus, understanding the regulation of the TRAIL apoptosis pathway can aid in the development of TRAIL-based therapies for the treatment of human cancer.

Ternary Emission of a Blue-, Green-, and Red-Based Molecular Imprinting Fluorescence Sensor for the Multiplexed and Visual Detection of Bovine Hemoglobin.

A novel ternary-emission fluorescence sensor was proposed by post-imprinting mixing blue-/green-/red-emission bovine hemoglobin (BHb) imprinted polymers (b-MIPs, g-MIPs, and r-MIPs) at a proper ratio and realized the multiplexed and visual detection of BHb. The three MIPs were individually embedded with blue-emission 7-hydroxycoumarin, green-emission CdTe quantum dots (QDs), and red-emission CdTe/ZnS QDs. Upon interaction with BHb within 8 min, the fluorescence of CdTe and CdTe/ZnS QDs were simultaneously turned off, whereas the 7-hydroxycoumarin turned on the fluorescence intensity. Thereupon, the ratiometric fluorescence intensity of the ternary emission linearly varied within 0.025-3 µM BHb, accompanying the profuse fluorescence color evolution from yellowish green to yellow to salmon to plum to purple to finally blue. In comparison with the dual- or single-emission sensor, the ternary-emission fluorescence MIPs sensor provided a wider color variation covering the green-red-blue window for accurate naked-eye determination of BHb, as well as a lower detection limit down to 7.8 nM and a higher imprinting factor of 15.2. Moreover, the satisfactory recoveries of 99.25-111.7% in determining the spiked BHb in bovine urine samples, as well as the optical stability and post-imprinting construction convenience, indicated that the developed tricolor-emission fluorescence MIPs sensor provided an ideal alternative for rapid, sensitive, and visual determination of proteins in complicated samples.