LX1 Targets Androgen Receptor Variants and AKR1C3 to overcome Therapy Resistance in Advanced Prostate Cancer.

The development of resistance to current standard-of-care treatments, such as androgen receptor (AR) targeting therapies, remains a major challenge in the management of advanced prostate cancer. There is an urgent need for therapeutic strategies targeting key resistance drivers, such as AR variants like AR-V7 and steroidogenic enzymes like AKR1C3, to improve outcomes for patients with advanced prostate cancer. Here, we designed, synthesized, and characterized a class of LX compounds targeting both AR/AR variants and AKR1C3. Molecular docking indicated that LX compounds bound to the AKR1C3 active sites. LX1 blocked AKR1C3 enzymatic activity, suppressing the conversion of androstenedione into testosterone. LX compounds also reduced AR/AR-V7 expression and downregulated their target genes. In vitro, LX1 inhibited the growth of prostate cancer cells resistant to antiandrogens, including enzalutamide, abiraterone, apalutamide, and darolutamide. Treatment with LX1 in vivo significantly decreased tumor growth, lowered serum PSA levels, and reduced intratumoral testosterone levels, without affecting mouse body weight. Furthermore, LX1 overcame resistance to enzalutamide treatment, and the combination of LX1 with enzalutamide further suppressed tumor growth. Collectively, the dual effect of LX1 in reducing intratumoral testosterone and AR signaling, along with its synergy with standard therapies in resistant models, underscores its potential as a valuable treatment option for advanced prostate cancer.

Does one-stitch method of temporary ileostomy affect the stoma-related complications after laparoscopic low anterior resection in rectal cancer patients?

PURPOSE: This current study attempted to investigate whether one-stitch method (OM) of temporary ileostomy influenced the stoma-related complications after laparoscopic low anterior resection (LLAR). METHODS: We searched for eligible studies in four databases including PubMed, Embase, Cochrane Library, and CNKI from inception to July 20, 2023. Both surgical outcomes and stoma-related complications were compared between the OM group and the traditional method (TM) group. The Newcastle-Ottawa Scale (NOS) was adopted for quality assessment. RevMan 5.4 was conducted for data analyzing. RESULTS: Totally 590 patients from six studies were enrolled in this study (272 patients in the OM group and 318 patients in the TM group). No significant difference was found in baseline information (P > 0.05). Patients in the OM group had shorter operative time in both the primary LLAR surgery (MD = - 17.73, 95%CI = - 25.65 to - 9.80, P < 0.01) and the stoma reversal surgery (MD = - 18.70, 95%CI = - 22.48 to -14.92, P < 0.01) than patients in the TM group. There was no significant difference in intraoperative blood loss of the primary LLAR surgery (MD = - 2.92, 95%CI = - 7.15 to 1.32, P = 0.18). Moreover, patients in the OM group had fewer stoma-related complications than patients in the TM group (OR = 0.55, 95%CI = 0.38 to 0.79, P < 0.01). CONCLUSION: The OM group had shorter operation time in both the primary LLAR surgery and the stoma reversal surgery than the TM group. Moreover, the OM group had less stoma-related complications.

Adaptive Neural Control for Hysteretic Nonlinear Systems With Hysteresis Neural Direct Inverse Compensator and Its Application.

Aiming at high precision control for a class of hysteretic nonlinear systems, a new hysteresis direct inverse compensator-based adaptive output feedback control scheme is designed in this article. First, a novel long short-term memory neural network (LSTMNN)-based hysteresis inverse compensator is established to compensate the asymmetric hysteresis nonlinearity, where the LSTMNN is used as the prediction mechanism for model operator weights, rather than the overall mapping of hysteresis input and output. Second, by designing the modified high-gain K -Filter states observer and the error transformed function, the unmeasurable states are estimated with arbitrarily small estimation error and the prespecified tracking performance is achieved. Lastly, the biconical dielectric elastomer actuator (DEA) motion platform is constructed. Then, the effectiveness of the proposed LSTMNN-based hysteresis inverse compensator and control scheme are verified on the experimental platform. The experimental results illustrate the effectiveness and advantages of proposed control scheme.

Multicenter registry of multisystem inflammatory syndrome in children (MIS-C) and Paired comparison with Kawasaki disease.

OBJECTIVES: This study aimed to identify clinical characteristics to differentiate multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) in Taiwan, an island with a delayed cluster of MIS-C and a high incidence of KD. Additionally, we studied risk factors for developing severe complications in patients with MIS-C. METHODS: We conducted a retrospective, multicenter, cohort, and observational study that linked data on patients with MIS-C between May and December 2022 and patients with KD between 2019 and 2021 from 12 medical centers. Hemodynamic compromise, defined as the need for inotropic support or fluid challenge, was recorded in patients with MIS-C. We also evaluated maximal coronary Z-scores before treatment and one month after disease onset. RESULTS: A total of 83 patients with MIS-C and 466 patients with KD were recruited. A 1:1 age and gender-matched comparison of 68 MIS-C and KD pairs showed that MIS-C patients had a lower percentage of positive BCG red halos, lower leukocyte/platelet counts, more gastrointestinal symptoms, and a higher risk of hemodynamic compromise. In Taiwan, 38.6% of MIS-C patients experienced hemodynamic compromise, with presence of conjunctivitis and elevated levels of procalcitonin (>1.62 ng/mL) identified as independent risk factors. CONCLUSIONS: We identified two independent risk factors associated with hemodynamic compromise in MIS-C patients. The comparison between matched MIS-C and KD patients highlighted significant differences in clinical presentations, like BCG red halos, which may aid in the differential diagnosis of the two disease entities, especially in regions with a high incidence rate of KD.

High-throughput screen identifies non inflammatory small molecule inducers of trained immunity.

Trained immunity is characterized by epigenetic and metabolic reprogramming in response to specific stimuli. This rewiring can result in increased cytokine and effector responses to pathogenic challenges, providing nonspecific protection against disease. It may also improve immune responses to established immunotherapeutics and vaccines. Despite its promise for next-generation therapeutic design, most current understanding and experimentation is conducted with complex and heterogeneous biologically derived molecules, such as ß-glucan or the Bacillus Calmette-Guérin (BCG) vaccine. This limited collection of training compounds also limits the study of the genes most involved in training responses as each molecule has both training and nontraining effects. Small molecules with tunable pharmacokinetics and delivery modalities would both assist in the study of trained immunity and its future applications. To identify small molecule inducers of trained immunity, we screened a library of 2,000 drugs and drug-like compounds. Identification of well-defined compounds can improve our understanding of innate immune memory and broaden the scope of its clinical applications. We identified over two dozen small molecules in several chemical classes that induce a training phenotype in the absence of initial immune activation-a current limitation of reported inducers of training. A surprising result was the identification of glucocorticoids, traditionally considered immunosuppressive, providing an unprecedented link between glucocorticoids and trained innate immunity. We chose seven of these top candidates to characterize and establish training activity in vivo. In this work, we expand the number of compounds known to induce trained immunity, creating alternative avenues for studying and applying innate immune training.

A fragment of the ß-glucosidase gene from the rumen fungus Neocallimastix patriciarum J11 encodes a recombinant protein that exhibits activities in ß-glucosidase and ß-glucanase.

Lignocellulose, the most abundant organic waste on Earth, is of economic value because it can be converted into biofuels like ethanol by enzymes such as ß-glucosidase. This study involved cloning a ß-glucosidase gene named JBG from the rumen fungus Neocallimastix patriciarum J11. When expressed recombinantly in Escherichia coli, the rJBG enzyme exhibited significant activity, hydrolyzing 4-nitrophenyl-ß-d-glucopyranoside and cellobiose to release glucose. Surprisingly, the rJBG enzyme also showed hydrolytic activity against ß-glucan, breaking it down into glucose, indicating that the rJBG enzyme possesses both ß-glucosidase and ß-glucanase activities, a characteristic rarely found in ß-glucosidases. When the JBG gene was expressed in Saccharomyces cerevisiae and the transformants were inoculated into a medium containing ß-glucan as the sole carbon source, the ethanol concentration in the culture medium increased from 0.17 g/L on the first day to 0.77 g/L on the third day, reaching 1.3 g/L on the fifth day, whereas no ethanol was detected in the yeast transformants containing the recombinant plasmid pYES-Sur under the same conditions. These results demonstrate that yeast transformants carrying the JBG gene can directly saccharify ß-glucan and ferment it to produce ethanol. This gene, with its dual ß-glucosidase and ß-glucanase activities, simplifies and reduces the cost of the typical process of converting lignocellulose into bioethanol using enzymes and yeast.

Comparing the Diagnostic Value of FDG PET or PET/CT With FDG PET/MR in Inflammatory Bowel Disease-A Systematic Review and Meta-analysis.

BACKGROUND: The aim of this study was to compare the diagnostic value of 18F-FDG PET or PET/CT with FDG PET/MR in patients with inflammatory bowel disease (IBD). METHODS: A comprehensive search was performed in PubMed for studies reporting the diagnostic performance of FDG PET (PET/CT) and FDG PET/MR in IBD from the inception of the database to March 14, 2024, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Fourteen studies were included in this systematic review and meta-analysis. Pooled estimates of segment-based sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for FDG PET (PET/CT) and FDG PET/MR were calculated alongside 95% confidence intervals. Summary receiver operating characteristic (SROC) curves were plotted, and the area under the SROC curve was determined alongside the Q* index. RESULTS: The segment-based pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the SROC curve of FDG PET (PET/CT) for diagnosing IBD (9 studies) were 0.81, 0.86, 5.76, 0.22, 31.92, and 0.92, respectively. Those of FDG PET/MR (5 studies) were 0.78, 0.92, 10.97, 0.25, 51.79, and 0.95. There was no significant difference in the abilities of detecting or excluding IBD between FDG PET (PET/CT) and FDG PET/MR. CONCLUSIONS: For diagnostic value in patients with IBD, there was no significant difference between FDG PET (PET/CT) and FDG PET/MR. Both FDG PET (PET/CT) and FDG PET/MR have demonstrated high diagnostic performance for accurate diagnosing in patients with IBD.

Optimizing surgical strategies for retroperitoneal liposarcoma: a comprehensive evaluation of standardized aggressive surgical policies.

BACKGROUND: Retroperitoneal liposarcoma (RLPS) constitutes the majority of retroperitoneal sarcomas. While surgical resection remains the sole curative approach, determining the optimal surgical strategy for RLPS remains elusive. This study addresses the ongoing debate surrounding the optimal surgical strategy for RLPS. METHODS: We recruited 77 patients with RLPS who underwent aggressive surgical policies. Patients were categorized into three surgical subtypes: suprapancreatic RLPS, pancreatic RLPS, and subpancreatic RLPS. Our standardized surgical strategy involved resecting macroscopically uninvolved adjacent organs according to surgical subtypes. We collected clinical, pathological and prognostic data for analyses. RESULTS: The median follow-up was 45.5 months. Overall survival (OS) and recurrence-free survival (RFS) were significantly correlated with multifocal RLPS, pathological subtype, recurrent RLPS and histological grade (P for OS = 0.011, 0.004, 0.010, and < 0.001, P for RFS = 0.004, 0.001, < 0.001, and < 0.001, respectively). The 5-Year Estimate OS of well-differentiated liposarcoma (WDLPS), G1 RLPS, de novo RLPS and unifocal RLPS were 100%, 89.4%, 75.3% and 69.1%, respectively. The distant metastasis rate was 1.4%. The morbidity rates (≥ grade III) for suprapancreatic, pancreatic, and subpancreatic RLPS were 26.7%, 15.6%, and 13.3%, respectively. The perioperative mortality rate is 2.6%. CONCLUSIONS: Standardized aggressive surgical policies demonstrated prognostic benefits for RLPS, particularly for G1 RLPS, WDLPS, unifocal RLPS, and de novo RLPS. This approach effectively balanced considerations of adequate exposure, surgical safety, and thorough removal of all fat tissue. G1 RLPS, WDLPS, unifocal RLPS, and de novo RLPS could be potential indications for aggressive surgical policies.

Therapeutic Effect of Lecigel, Cetiol®CC, Activonol-6, Activonol-M, 1,3-Propanediol, Soline, and Fucocert® (LCAA-PSF) Treatment on Imiquimod-Induced Psoriasis-like Skin in Mice.

The individual ingredients of 1,3-Propanediol, Soline, and Fucocert® (PSF) are often used as cosmetic formulations in skin care. In addition, the mixture of Lecigel, Cetiol®CC, Activonol-6, and Activonol-M (LCAA) is often used as a cosmetic base. However, whether the combination of LCAA with PSF (LCAA-PSF) exerts a therapeutic effect on psoriasis remains unclear. In this study, mice induced with imiquimod (IMQ) were divided into three groups and administered 100 mg/day of LCAA, 100 mg/day of LCAA-PSF, or Vaseline on the dorsal skin of each mouse. Weight-matched mice treated with Vaseline alone were used as controls. Hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay(ELISA) were used to assess tissue morphology and inflammatory cytokines. RNA sequencing analysis was used to predict the mechanism underlying the action of LCAA-PSF against psoriasis, while immunohistochemical analysis validation was used to identify pertinent molecular pathways. The results demonstrated that LCAA-PSF alleviated IMQ-induced keratinocyte differentiation/ proliferation bydecreasingthe serum levels of inflammatory cytokines such as IL-6, TNF-α, IL-23, and IL-17A and the epidermisof TGFß, Ki67, CK5/6, and VEGF expression, which is associated with angiogenesis and keratinocyte differentiation/ proliferation. These findings highlight the antipsoriatic activity of LCAA-PSF in a psoriasis-like mouse model and suggest this may occurvia the inhibition of inflammatory factor secretionand the TGFß-related signal pathway.

The Clinical Impact of Different Types of Preoperative Biliary Intervention on Postoperative Biliary Tract Infection of Patients Undergoing Pancreaticoduodenectomy.

Background: For patients with obstructive jaundice and who are indicated for pancreaticoduodenectomy (PD) or biliary intervention, either endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography and drainage (PTCD) may be indicated preoperatively. However, the possibility of procedure-related postoperative biliary tract infection (BTI) should be a concern. We tried to evaluate the impact of ERCP and PTCD on postoperative BTI. Methods: Patients diagnosed from June 2013 to March 2022 with periampullary lesions and with PD indicated were enrolled in this cohort. Patients without intraoperative bile culture and non-neoplastic lesions were excluded. Clinical information, including demographic and laboratory data, pathologic diagnosis, results of microbiologic tests, and relevant infectious outcomes, was extracted from medical records for analysis. Results: One-hundred-and-sixty-four patients from the cohort (164/689) underwent preoperative biliary intervention, either ERCP (n = 125) or PTCD (n = 39). The positive yield of intraoperative biliary culture was significantly higher in patients who underwent ERCP than in PTCD (90.4% vs. 41.0%, p < 0.001). Although there was no significance, a trend of higher postoperative BTI (13.8% vs. 2.7%) and BTI-related septic shock (5 vs. 0, 4.0% vs. 0%) in the ERCP group was noticed. While the risk factors for postoperative BTI have not been confirmed, a trend suggesting a higher incidence of BTI associated with ERCP procedures was observed, with a borderline p-value (p = 0.05, regarding ERCP biopsy). Conclusions: ERCP in patients undergoing PD increases the positive yield of intraoperative biliary culture. PTCD may be the favorable option if preoperative biliary intervention is indicated.

Macrolide-Resistant Mycoplasma pneumoniae Infections among Children before and during COVID-19 Pandemic, Taiwan, 2017-2023.

Before the COVID-19 pandemic, Mycoplasma pneumoniae infections emerged during spring to summer yearly in Taiwan, but infections were few during the pandemic. M. pneumoniae macrolide resistance soared to 85.7% in 2020 but declined to 0% during 2022-2023. Continued molecular surveillance is necessary to monitor trends in macrolide-resistant M. pneumoniae.

The effect of low-level laser therapy on osteoclast differentiation: Clinical implications for tooth movement and bone density.

Background/purpose: Osteoclast differentiation is crucial for orchestrating both tooth movement and the maintenance of bone density. Therefore, the current study sought to explore the impact of low-level laser therapy (LLLT) on osteoclast differentiation, functional gene expression, molecular signaling pathways, and orthodontic tooth movement in clinical settings. Materials and methods: The RAW 264.7 cell line served as the precursor for osteoclasts, and these cells underwent irradiation using a 808-nm LLLT. Osteoclast differentiation was assessed through tartrate-resistant acid phosphatase (TRAP) staining. Functional gene expression levels were evaluated using real-time quantitative polymerase chain reaction (RT-qPCR) while signaling molecules were examined through Western blot analysis. In the clinical study, 12 participants were enrolled. Their tooth movement was monitored using a TRIOS desktop scanner. Bone density measurements were conducted using Mimics software, which processed cone-beam computed tomography (CBCT) images exported in Digital Imaging and Communications in Medicine (DICOM) format. Results: We found that LLLT effectively promoted receptor activator of nuclear factor-κB ligand (RANKL)-dependent osteoclast differentiation and the expression of osteoclast functional genes, including matrix metallopeptidase 9 (MMP9), nuclear factor of activated T-cells cytoplasmic 1(NFATc1), tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CTSK) in RAW264.7 cells. Clinically, the cumulative tooth movement over 90 days was significantly higher in the laser group than in the control group. Conclusion: Our research demonstrates that LLLT not only significantly promotes osteoclast differentiation but is also a valuable adjunct in orthodontic therapy.

Triple click chemistry for crosslinking, stiffening, and annealing of gelatin-based microgels.

Microgels are spherical hydrogels with physicochemical properties ideal for many biomedical applications. For example, microgels can be used as individual carriers for suspension cell culture or jammed/annealed into granular hydrogels with micron-scale pores highly permissive to molecular transport and cell proliferation/migration. Conventionally, laborious optimization processes are often needed to create microgels with different moduli, sizes, and compositions. This work presents a new microgel and granular hydrogel preparation workflow using gelatin-norbornene-carbohydrazide (GelNB-CH). As a gelatin-derived macromer, GelNB-CH presents cell adhesive and degradable motifs while being amenable to three orthogonal click chemistries, namely the thiol-norbornene photo-click reaction, hydrazone bonding, and the inverse electron demand Diels-Alder (iEDDA) click reaction. The thiol-norbornene photo-click reaction (with thiol-bearing crosslinkers) and hydrazone bonding (with aldehyde-bearing crosslinkers) were used to crosslink the microgels and to realize on-demand microgel stiffening, respectively. The tetrazine-norbornene iEDDA click reaction (with tetrazine-bearing crosslinkers) was used to anneal microgels into granular hydrogels. In addition to materials development, we demonstrated the value of the triple-click chemistry granular hydrogels via culturing human mesenchymal stem cells and pancreatic cancer cells.

Does chronic kidney disease affect the short-term outcomes and prognosis of colorectal cancer surgery? A propensity score matching analysis.

Purpose: The aim of this study was to analyze the effect of chronic kidney disease (CKD) on the short-term outcomes and prognosis of colorectal cancer (CRC) patients who underwent primary surgery. Methods: CRC patients who underwent radical surgery were included from Jan 2011 to Jan 2020 in a single hospital. The short-term outcomes and prognosis were compared between the CKD group and the Non-CKD group using propensity score matching (PSM) analysis. Results: A total of 4056 patients undergoing CRC surgery were included, including 723 patients in the CKD group and 3333 patients in the Non-CKD group. After 1:1 PSM, there were 666 patients in each group, respectively. No significant difference was found in baseline characteristics between the two groups. (p>0.05). After PSM, the CKD group had a longer postoperative hospital stay (P=0.009) and a higher incidence of overall complications (p=0.050). Cox analysis was performed on matched patients to find predictors of overall survival (OS) and disease-free survival (DFS). We found that age (p<0.01, HR=1.045, 95% CI=1.028-1.062), tumor stage (p<0.01, HR=1.931, 95% CI=1.564-2.385) and overall complications (p<0.01, HR=1.858, 95% CI=1.423-2.425) were independent predictors of OS. Age (p<0.01, HR=1.034, 95% CI=1.020-1.049), tumor stage (p<0.01, HR=1.852, 95% CI=1.537-2.231), and overall complications (p<0.01, HR=1.651, 95% CI=1.295-2.10) were independent predictors of DFS. However, CKD was not an independent predictor of OS or DFS (OS: p=0.619, HR=1.070, 95% CI=0.820-1.396; DFS: p=0.472, HR=1.092, 95% CI=0.859-1.389). Conclusion: CKD prolonged postoperative hospital stay; however, CKD might not affect major postoperative complications, OS or DFS of CRC.

Tennis player actions dataset for human pose estimation.

Tennis is a popular sport, and integrating modern technological advancements can greatly enhance player training. Human pose estimation has seen substantial developments recently, driven by progress in deep learning. The dataset described in this paper was compiled from videos of researchers' friend playing tennis. These videos were retrieved frame by frame to categorize various tennis movements, and human skeleton joints were annotated using COCO-Annotator to generate labelled JSON files. By combining these JSON files with the classified image set, we constructed the dataset for this paper. This dataset enables the training and validation of four tennis postures, forehand shot, backhand shot, ready position, and serves, using deep learning models (such as OpenPose). The researchers believe that this dataset will be a valuable asset to the tennis community and human pose estimation field, fostering innovation and excellence in the sport.

The effect of lymph node ratio on the surgical outcomes in patients with colorectal cancer.

The current study aimed to evaluate the effect of lymph node ratio (LNR) on the short-term and long-term outcomes of colorectal cancer (CRC) patients who underwent radical CRC surgery. We retrospectively collected CRC patients who underwent radical surgery from Jan 2011 to Jan 2020 in a single-center hospital. The patients were divided into the high LNR group and the low group according to the median. The baseline information and the short-term outcomes were compared between the high group and the low group. Univariate and multivariate logistic regression was performed to analyze the independent predictors for overall survival (OS) and disease-free survival (DFS). A 1:1 proportional propensity score matching (PSM) was used to reduce the selection bias between the two groups. Kaplan-Meier method was used to estimate the OS and DFS between the two groups in different T stages. A total of 1434 CRC patients undergoing radical surgery were enrolled in this study, and there were 730 (50.9%) patients in the low LNR group and 704 (49.1%) patients in the high LNR group. After the PSM, there were 618 patients in both groups, the baseline characteristics between the two groups had no significant difference (p > 0.05). After comparing the Surgery-related information and The Short-term outcomes, the high LNR group had a longer hospital stay (after PSM, p < 0.01). In univariate and multivariate logistic regression analyses, age (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), tumor location (univariate analysis, p = 0.020; multivariate analysis, p = 0.024), lymph-vascular space invasion (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), cancer nodules (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), tumor size (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), LNR (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), and overall complications (univariate analysis, p < 0.01; multivariate analysis, p < 0.01) were independent risk factors for OS, and age (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), tumor location (univariate analysis, p = 0.032; multivariate analysis, p = 0.031), T stage (univariate analysis, p < 0.01; multivariate analysis, p = 0.014), lymph-vascular space invasion (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), cancer nodules (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), LNR (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), and overall complications (univariate analysis, p < 0.01; multivariate analysis, p < 0.01) were identified as independent risk factors for DFS. The high LNR group had a worse OS in T3 (p < 0.01) and T4 (p < 0.01) as well as a worse DFS in T3 (p < 0.01) and T4 (p < 0.01). No association was found between LNR and postoperative complications, but the high LNR group had a longer hospital stay. LNR was identified as an independent predictor for OS and DFS. Furthermore, high LNR had a worse OS and DFS under T3 and T4 stages. Therefore, LNR was more prognostically significant for CRC patients under T3 and T4 stages.

Redefining aberrant P53 expression of gastric cancer and its distinct clinical significance among molecular-histologic subtypes.

BACKGROUND: Numerous studies have demonstrated a correlation between p53 overexpression and diminished survival in gastric cancer patients. However, conflicting findings exist, and we hypothesize that these discrepancies arise from the cancer's complexity and heterogeneity, coupled with a lack of consensus on aberrant p53 expression. METHODS: We enrolled a cohort of 187 patients with surgically resected gastric cancer. Patient categorization was based on Epstein-Barr virus (EBV), microsatellite instability (MSI), and Lauren classification (intestinal, diffuse and mixed). Utilizing an incremental algorithm, we evaluated p53 immunohistochemical (IHC) patterns in all 187 cases, while next-generation sequencing was successfully performed on 152 cases to identify TP53 mutations (mutTP53). RESULTS: MutTP53 was identified in 32 % of the 152 cases, comprising 36 missense, 5 nonsense, and 7 frameshift alterations. Missense mutations predominantly correlated with p53 overexpression, while nonsense and frameshifting alterations related to null expression. Trial calculations indicated that null expression and a p53 IHC cutoff at >40 % offered the best prediction of mutTP53 (kappa coefficient, 0.427), with the highest agreement (0.524) observed in diffuse type and the lowest (0.269) in intestinal type. Null expression and a p53 IHC cutoff at >10 %, but not mutTP53 per se, provided the optimal prediction of survival outcome (p = 0.043), particularly in diffuse type (p = 0.044). Multivariate analysis showed that aberrant p53 IHC expression was not an independent prognostic factor. CONCLUSIONS: P53 IHC patterns are predictive biomarkers for mutTP53 and gastric cancer outcomes, where a prerequisite involves a nuanced approach considering cutoff values and molecular-histologic subtyping.

Clinical characteristics and risk factors of severe human parainfluenza virus infection in hospitalized children.

BACKGROUND: Human parainfluenza viruses (HPIVs) commonly cause childhood respiratory illness requiring hospitalization in Taiwan. This study aimed to investigate clinical severity and identify risk factors predisposing to severe disease in hospitalized children with HPIV infection. METHODS: We included hospitalized patients with lab-confirmed HPIV infection from 2007 to 2018 and collected their demographic and clinical characteristics. Patients with ventilator support, intravenous inotropic agents, and extracorporeal membrane oxygenation were defined as severe cases. RESULTS: There were 554 children hospitalized for HPIV infection. The median age was 1.2 years; 518 patients had non-severe HPIV infection, whereas 36 patients (6.5%) had severe HPIV infection. 266 (48%) patients had underlying diseases, and 190 patients (34.3%) had bacterial co-detection. Children with severe HPIV infection were more likely to have bacterial co-detection than those without (52.8% vs 33.0%, p = 0.02). Patients with lung patch or consolidation had more invasive bacterial co-infection or co-detection than those without patch or consolidation (43% vs 33%, p = 0.06). Patients with neurological disease (adjusted OR 4.77, 95% CI 1.94-11.68), lung consolidation/patch (adjusted OR 6.64, 95% CI 2.80-15.75), and effusion (adjusted OR 11.59, 95% CI 1.52-88.36) had significantly higher risk to have severe HPIV infection. CONCLUSION: Neurological disease and lung consolidation/patch or effusion were the most significant predictors of severe HPIV infection.

The impact of previous abdominal surgery on colorectal cancer patients undergoing laparoscopic surgery.

The current study aimed to investigate whether previous abdominal surgery (PAS) could affect the outcomes of colorectal cancer (CRC) surgery. We conducted the search strategy in three databases (PubMed, Embase, and the Cochrane Library) from inception to May 26, 2022. The short-term and long-term outcomes were compared between the PAS group and the non-PAS group. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled up. Stata (V.16.0) software was used for data analysis. We included 34,827 patients from 14 studies in the current study. After pooling up all the data, we found that there were higher proportions of overall complications (OR = 1.12, I2 = 4.65%, 95% CI 1.03 to 1.23, P = 0.01), ileus (OR = 1.96, I2 = 59.74%, 95% CI 1.12 to 3.44, P = 0.02) and mortality (OR = 1.26, I2 = 0.00%, 95% CI 1.11 to 1.42, P = 0.00) in the PAS group than the non-PAS group. Patients with a history of PAS had higher risks of overall complications and death following CRC surgery. However, it did not appear to significantly affect the short-term outcomes apart from ileus. Surgeons should raise awareness of patients with a history of PAS, and take steps to reduce postoperative complications and mortality.