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Objective: Drug-induced liver injury (DILI) is one of the most challenging forms of liver disorder. We aimed to use ultrasound dual elastography, by combining strain and shear wave imaging, to noninvasively assess liver inflammation and injury severity of DILI. Methods: 291 DILI patients were included in the prospective multicenter study and divided into training and validation cohorts. All patients received liver biopsy and dual elastography examination. Liver inflammation grading (G0-4) and fibrosis staging (F0-4) were considered as the gold standard of liver injury and G+F ≥ 5 was defined as severe liver injury. Indexes of dual elastography and serological indicators (DESI) were selected and analyzed with multivariable logistic regression to build DESI models for evaluating liver inflammation, and the C score model was built with the same method for diagnosing severe liver injury. Results: Areas under the receiver operating characteristic curve (AUCs) of the DESI model to assess liver inflammation ≥ G2 were 0.887 and 0.868 in training and validation cohorts, respectively. AUCs of the DESI model in diagnosing ≥ G3 were 0.893 and 0.896 in the two cohorts, respectively. The C score accurately assessed severe liver injury with AUCs of 0.909 and 0.885 in two cohorts. Of the 87 patients with mild clinical severity, 10 (11.49%) had severe pathological injury, which could be identified by C score. Conclusion: Dual elastography demonstrated high performance in diagnosing liver inflammation and identifying severe pathological liver injury of DILI, making up for the deficiency of serological indicators alone for evaluating DILI severity.

This case report describes a 62-year-old male with a notable medical history, including surgically treated bladder cancer and the suspicion of metastatic disease. He underwent 18F-FDG PET/CT imaging as part of the initial diagnostic workup, which identified several marginally hypodense hepatic lesions. These lesions exhibited metabolic activity that was slightly lower than the surrounding hepatic parenchyma, raising concerns for metastatic involvement. Subsequent 18F-DOTATATE PET/CT imaging significantly expanded the diagnostic perspective by identifying multiple somatostatin receptor (SSTR)-positive lesions, not only in the liver but also in lymph nodes and bones. This marked an important diagnostic advancement over the initial FDG PET/CT findings, showcasing the superior sensitivity of 18F-DOTATATE PET/CT in detecting SSTR-expressing tumors. Pathological evaluation after these imaging studies confirmed the diagnosis of a rectal neuroendocrine tumor (NET) with extensive hepatic metastasis, altering the clinical management and therapeutic approach for the patient. This case underscores the pivotal role of integrating 18F-DOTATATE and FDG PET/CT in the diagnostic and therapeutic management of neuroendocrine tumors, highlighting the complementary nature of these imaging modalities. The findings advocate for the use of 18F-DOTATATE PET/CT in cases where NETs are suspected, particularly for its enhanced sensitivity in detecting SSTR-positive lesions across various sites, thereby facilitating a more comprehensive disease assessment and informed therapeutic planning.

Objective This study aimed to evaluate the development of atherosclerosis in ApoE-deficient dogs fed with a high-fat diet (HFD) using vascular duplex ultrasonography (VDU). Methods Thirty beagle dogs were enrolled, including 10 wild-type, 16 heterozygous (ApoE-/+), and four homozygous (ApoE-/-) mutant dogs. The dogs were categorized into either the normal diet (ND) or HFD group. Plasma lipids levles were tested at baseline and then after feeding the dog a different diet for 6 months. The carotid arteries, abdominal aorta (AO) and iliac arteries were examined using VDU. Artery sections of the ApoE-/- dogs were analyzed. Results After HFD, lipids especially triglycerides, total cholesterol and low-density lipoprotein (LDL) in the wild type and ApoE-/+ dogs were significantly increased. Both the intima-media thickness (IMT) of the common carotid artery (CCA) and AO in the wild type and ApoE-/+ dogs significantly increased. In the ApoE-/+ dogs, the mean percentages increases in CCA-IMT and AO-IMT after HFD were higher than those in the ND dogs. The mean values of CCA-IMT and AO-IMT in the ApoE-/-dogs increased to 2-2.5 folds after HFD. Histological analysis confirmed that the carotid and iliac arteries had advanced atherosclerotic lesions in the ApoE-/- dogs. Conclusions HFD may accelerate the development of atherosclerosis in ApoE-deficient dogs, which is an optimal large-animal model of atherosclerosis.

Background: Pelvic fractures in trauma patients can be associated with substantial massive hemorrhage. Hemostasis interventions mainly consist of pelvic packing (PP) and endovascular intervention (EI), such as angiography-embolization (AE) and resuscitative endovascular balloon occlusion of the aorta (REBOA). Whether PP or EI should be prioritized for the management of hemodynamic unstable patients with pelvic fractures remains under debate. This meta-analysis aimed to establish the evidence-based recommendations for the management of hemodynamic unstable patients. Materials and methods: PubMed, CENTRAL, and EMBASE databases were searched for articles published from January 1, 2000 to January 31, 2023. Eligible studies, such as retrospective cohort studies, propensity score matching studies, prospective cohort studies, observational cohort studies, quasi-randomized clinical trials evaluating PP and EI (AE or REBOA) for the management of patients with hemodynamically unstable pelvic fractures, were included. Mean Difference (MD), relative risk (RR), and 95 % confidence intervals (CI) were calculated using fixed- or random-effects models depending on the heterogeneity of included trials. We compared the effectiveness of the two methods in terms of mortality, unstable fracture pattens, injury severity score (ISS), systolic blood pressure (SBP), lactate (LA), base deficiency (BE), hemoglobin preoperatively, blood transfusion requirement, the time to and of operation, complications. Results: Overall, 15 trials enrolling 1136 patients were analyzed, showing a total mortality rate of 28.4 % (323/1136). No effect of PP preference on the ISS (PP 36.4 ± 10.4 vs. EI 34.5 ± 12.7), SBP (PP 81.1 ± 24.3 mmHg vs. EI 94.2 ± 32.4 mmHg), LA (PP 4.66 ± 2.72 mmol/L vs. 4.85 ± 3.45 mmol/L), BE (PP 8.14 ± 5.64 mmol/L vs. 6.66 ± 5.68 mmol/L), and unstable fracture patterns (RR = 1.10, 95 % CI [0.63, 1.92]) was observed. PP application was associated with lower preoperative hemoglobin level (PP 8.11 ± 2.28 g/dL vs. EI 8.43 ± 2.43 g/dL, p 0.05). Conclusions: PP showed advantages of reducing the amount of postoperative transfusion, shortening the time of waiting and operating, and decreasing mortality due to uncontrolled hemorrhage in the acute phase without raising the odds of mortality due to complications. PP, a reliable hemostatic method, should be prioritized for resuscitating most pelvic fractures with hemodynamically unstable, especially in case of bleeding from veins and fracture sites, as well as inadequate EI.

Ye-Meng Mao, Ming-Dao Zhang Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, World Health Organization Collaborating Center for Research and Training in Mental Health, Shanghai, People’s Republic of China Abstract: We focused on the application of antidepressants in schizophrenia treatment in this review. Augmentation of antidepressants with antipsychotics is a common clinical practice to treat resistant symptoms in schizophrenia, including depressive symptoms, negative symptoms, comorbid obsessive–compulsive symptoms, and other psychotic manifestations. However, recent systematic review of the clinical effects of antidepressants is lacking. In this review, we have selected and summarized current literature on the use of antidepressants in patients with schizophrenia; the patterns of use and effectiveness, as well as risks and drug–drug interactions of this clinical practice are discussed in detail, with particular emphasis on the treatment of depressive symptoms in schizophrenia. Keywords: depressive symptoms, drug-drug interaction, antipsychotics

Purpose Develop an albumin nanoparticle-based nanoprobe for targeted glioblastoma (GBM) diagnosis and treatment, utilizing Angopep-2 for low-density lipoprotein receptor-related protein (LRP) targeting. Methods Combined albumin-coated superparamagnetic iron oxide (SPIO), Carmustine (BCNU), and indocyanine green (ICG). Assessed morphology, size, Zeta potential, fluorescence, and drug encapsulation. Conducted in vitro fluorescence/MRI imaging and cell viability assays, and in vivo nanoprobe accumulation evaluation in brain tumors. Results ANG-BSA/BCNU/ICG MNPs exhibited superior targeting and cytotoxicity against GBM cells in vitro. In vivo, enhanced brain tumor accumulation during imaging was observed. Conclusion This targeted imaging and drug delivery system holds promise for efficient GBM therapy and intraoperative localization, addressing Blood-brain barrier (BBB) limitations with precise drug delivery and imaging capabilities.

Background: Ginsenosides (GS), including total GS, Rh2, Rg3 and compound K (CK), have been utilized as adjuvants in transarterial chemoembolization (TACE), surgery, and chemotherapy for hepatocellular carcinoma (HCC) therapy. However, the safety and efficacy of such combination treatments have been contradictory across different studies. This study aims to systematically evaluate the efficacy and safety of GS as adjuvant therapy for HCC. Methods : A literature search of PubMed, CNKI, Wanfang Data, Cochrane Library, Embase, and Web of Science was conducted up to May 2024 for clinical randomized controlled trials (RCTs) on GS-based adjuvant treatments for HCC. Two researchers independently screened the literature, extracted relevant data, and assessed study quality. Meta-analysis was conducted using RevMan 5.4. Results : Nineteen articles involving 1448 patients were included. Meta-analysis showed that GS as an adjuvant therapy for HCC improved disease control rate (risk ratio (RR) = 1.42, 95% CI [1.26, 1.60]), objective response rate (RR = 1.20, 95% CI [1.09, 1.32]), life quality (RR = 1.49, 95% CI [1.23, 1.79]), 1-year overall survival rate (RR = 1.27, 95% CI [1.06, 1.52]), 2-year overall survival rate (RR = 1.43, 95% CI [1.06, 1.95]), ehanced Child-Pugh in A level (RR = 1.59, 95% CI [1.08, 2.34]), Child-Pugh in B level (RR = 1.28, 95% CI [1.08, 1.52]); increased CD3 + (MD = 8.81, 95% CI [3.91, 13.71]), NKC (MD = 8.00, 95% CI [6.76, 9.24]) and CD4 + (MD = 9.38, 95% CI [8.04, 10.72]), and reduced incidence of adverse reactions including nausea and vomiting (RR = 0.66, 95% CI [0.57, 0.77]), anorexia (RR = 0.33, 95% CI [0.21, 0.50]), leukopenia (RR = 0.55, 95% CI [0.46, 0.67]) and myelosuppression (RR = 0.54, 95% CI [0.40, 0.74]); decreased Child-Pugh in C level (RR = 0.43, 95% CI [0.27, 0.68]) and CD4 + /CD8 + ratio (MD = 0.50, 95% CI [0.47, 0.57]). Conclusions : In summary, GS combined with Western medical approaches (TACE, surgery, chemotherapy) for the treatment of HCC can improve clinical efficacy, increase overall survival rates, enhance patient life quality, and reduce the occurrence of adverse reactions. However, due to the generally low quality of the included studies, more large-sample, multi-center, high-quality, RCTs are warranted to further consolidate these findings.

Background: Food allergy (FA) is a common disorder in children and affects the health of children worldwide. The gut microbiota is closely related to the occurrence and development of FA. Fecal microbiota transplantation (FMT) is a way to treat diseases by reconstituting the microbiota; however, the role and mechanisms of FA have not been validated. Methods: In this study, we established an ovalbumin (OVA)-induced juvenile mouse model and used 16S RNA sequencing, pathological histological staining, molecular biology, and flow-through techniques to evaluate the protective effects of FMT treatment on FA and to explore the mechanisms. Results: OVA-induced dysregulation of the gut microbiota led to impaired intestinal function and immune dysregulation in FA mice. FMT treatment improved the structure, diversity, and composition of the gut microbiota and restored it to a near-donor state. FMT treatment reduced levels of Th2-associated inflammatory factors, decreased intestinal tissue inflammation, and reduced IgE production. In addition, FMT reduced the number of mast cells and eosinophils and suppressed OVA-specific antibodies. Further mechanistic studies revealed that FMT treatment induced immune tolerance by inducing the expression of CD103+DCs and programmed cell death ligand 1 (PD-L1) in mesenteric lymph nodes and promoting the production of Treg through the programmed cell death protein 1 (PD-1)/PD-L1 pathway. Meanwhile, Th2 cytokines, OVA-specific antibodies, and PD-1/PD-L1 showed a significant correlation with the gut microbiota. Conclusions: FMT could regulate the gut microbiota and Th1/Th2 immune balance and might inhibit FA through the PD-1/PD-L1 pathway, which would provide a new idea for the treatment of FA.

Introduction: Previous results from the phase 3 ALESIA study (NCT02838420) revealed that alectinib (a central nervous system [CNS]-active, ALK inhibitor) had clinical benefits in treatment-naïve Asian patients with advanced ALK-positive NSCLC, consistent with the global ALEX study. We present updated data after more than or equal to 5 years of follow-up from the “last patient in” date. Methods: Adult patients with treatment-naïve, advanced ALK-positive NSCLC from mainland China, South Korea, and Thailand were randomized 2:1 to receive twice-daily 600 mg alectinib (n = 125) or 250 mg crizotinib (n = 62). The primary endpoint was investigator-assessed progression-free survival. Secondary or exploratory endpoints included overall survival, objective response rate, time to CNS progression, and safety. Results: At the data cutoff (May 16, 2022), the median survival follow-up was 61 and 51 months in the alectinib and crizotinib arms, respectively. Median progression-free survival was 41.6 months with alectinib versus 11.1 months with crizotinib (stratified hazard ratio = 0.33, 95% confidence interval: 0.23–0.49). Overall survival data remain immature; 5-year overall survival rates were 66.4% (alectinib arm) versus 56.1% (crizotinib arm). Objective response rate was 91.2% versus 77.4% with alectinib and crizotinib, respectively. CNS progression was delayed with alectinib versus crizotinib (cause-specific hazard ratio = 0.16, 95% confidence interval: 0.08–0.32). Median treatment duration was longer with alectinib versus crizotinib (42.3 versus 12.6 mo). No new safety signals were observed. Conclusions: With four additional years of follow-up, these updated results confirm the clinical benefit and manageable safety of alectinib in Asian patients with advanced ALK-positive NSCLC, and confirm alectinib as a standard-of-care treatment for patients with advanced ALK-positive NSCLC.

IGFBP6, a member of the IGF binding protein (IGFBP) family, is a specific inhibitor of insulin-like growth factor II (IGF-II) and can inhibit the growth of malignant tumors overexpressing IGF-II. Type 2 diabetes (T2D) is a basic disorder of glucose metabolism that can be regulated by IGF-related pathways. We performed bioinformatics analysis of the TCGA database to explore the possible mechanism of IGFBP6 in breast cancer (BC) metabolism and prognosis and collected clinical samples from BC patients with and without T2D to compare and verify the prognostic effect of IGFBP6. In our study, the levels of IGFBP1–6 were positively correlated with overall survival (OS) in patients with breast cancer. IGFBP6 was upregulated in estrogen receptor (ER)-positive BC, and ER-positive and progesterone receptor (PR) positive patients had a higher expression level of IGFBP6 than ER-negative and PR-negative patients. IGFBP6 could be used as an independent prognostic factor in BC. The expression of IGFBP6 was decreased in BC tissue, and BC tissue from patients with T2D had lower IGFBP6 expression levels than BC tissue from patients without T2D. IGFBP6 is mainly involved in the PI3K–Akt and TGF-β signaling pathways and tumor microenvironment regulation. In terms of metabolism, the expression of IGFBP6 was negatively correlated with that of most glucose metabolism-related genes. IGFBP6 expression was mainly correlated with mutations in TP53, PIK3CA, CDH1, and MAP3K1. In addition, the upregulation of IGFBP6 in BC increased the drug sensitivity to docetaxel, paclitaxel and gemcitabine. Overall, these results indicated that high expression of IGFBP6 is associated with a good prognosis in BC patients, especially in those without T2D. It is not only involved in the maintenance of the tumor microenvironment in BC but also inhibits the energy metabolism of cancer cells through glucose metabolism-related pathways. These findings may provide a new perspective on IGFBP6 as a potential prognostic marker for BC.

Objectives: Heparanase (HPSE), an endoglycosidase that cleaves heparan sulfate, regulates various biological processes related to tumor progression. We explore the prognostic value of HPSE and its relationship with immunotherapy response in patients with breast cancer, to improve the effectiveness of immunotherapy and increase the survival outcomes. Methods: In the study, we explored the prognostic value of HPSE through the The Cancer Genome Atlas (TCGA) database. By using the single-sample gene set enrichment analysis ( ssGSEA) method, we measured the infiltration levels of 24 immune cell types in the tumor microenvironment. Cancer Therapeutics Response Portal (CTRP) and PRISM datasets provide the area under the dose-response curve (AUC) to measure drug sensitivity. Using nomograms, we predicted overall survival ability. In vivo studies, we investigated the relationship between HPSE and immune checkpoint proteins and pro-inflammatory cytokines by immunohistochemistry of Triple-Negative Breast Cancer tumors in mice. Results: Our model demonstrated that the integrating of HPSE with the clinical stage effectively predicts patients’ survival time, highlighting high HPSE expression as a prognostic risk factor for breast cancer. Then the Receiver Operating Characteristic (ROC) curve [AUC of 1 year = 0.747, AUC of 3 years = 0.731] and Decision Curve Analysis (DCA) curve illustrated the satisfactory discriminative capacity of our model, emphasizing its valuable clinical applicability. Immune-related results showed that HPSE correlates strongly with immune infiltrating cells, immune-related genes, and the anti-cancer immunity cycle. In vivo studies have demonstrated that HPSE in breast cancer is associated with increased expression of immune checkpoint proteins CD274 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and is positively correlated with the pro-inflammatory cytokine TNF-α. Meanwhile, we analyzed the 11 types of drugs that are sensitive to the HPSE gene. Conclusion: Our results show that HPSE can serve as an effective biomarker to predict the prognosis of breast cancer patients and reflect the impact of immunotherapy.

Background ICU patients have a high incidence of VTE. The American College of Chest Physicians antithrombotic practice guidelines recommend assessing the risk of VTE in all ICU patients. Although several VTE risk assessment tools exist to evaluate the risk factors among hospitalized patients, there is no validated tool specifically for assessing the risk of VTE in ICU patients. Methods A retrospective corhort study was conducted between June 2018 and October 2022. We obtained data from the electronic medical records of patients with a variety of diagnoses admitted to a mixed ICU. Multivariable logistic regression analysis was used to evaluate the independent risk factors of VTE. Receiver operating characteristic (ROC) curves were used to analyse the predictive accuracy of different tools. Results A total of 566 patients were included, and VTE occurred in 89 patients (15.7%), 62.9% was asymptomatic VTE. A prediction model (the ICU-VTE prediction model) was derived from the independent risk factors identified using multivariate analysis. The ICU-VTE prediction model included eight independent risk factors: history of VTE (3 points), immobilization ≥4 days (3 points), multiple trauma (3 points), age ≥70 years (2 points), platelet count >250 × 10 3 /μL (2 points), central venous catheterization (1 point), invasive mechanical ventilation (1 point), and respiratory failure or heart failure (1 point). Patients with a score of 0–4 points had a low (1.81%) risk of VTE. Patients were at intermediate risk, scoring 5–6 points, and the overall incidence of VTE in the intermediate-risk category was 17.1% (odds ratio [OR], 11.1; 95% confidence interval [CI], 4.2-29.4). Those with a score ≥7 points had a high (44.1%) risk of VTE (OR, 42.6; 95% CI, 16.4-110.3). The area under the curve (AUC) of the ICU-VTE prediction model was 0.838, and the differences in the AUCs were statistically significant between the ICU-VTE prediction model and the other three tools (ICU-VTE score, Z = 3.723, P

Background: Given the complexity of arthroscopic rotator cuff repair (ARCR) and increasing prevalence, there is a need for comprehensive, large-scale studies that investigate potential correlations between surgeon-specific factors and postoperative outcomes after ARCR. This study examines how surgeon-specific factors including case volume, career length, fellowship training, practice setting, and regional practice impact two-year reoperation rates, conversion to total shoulder arthroplasty (anatomic or reverse), and 90-day post-ARCR hospitalization. Methods: The PearlDiver Mariner database was used to collect surgeon-specific variables and query patients who underwent ARCR from 2015 to 2018. Patient outcomes were tracked for two years, including reoperations, hospitalizations, and International Classification of Diseases, Tenth Revision codes for revision rotator cuff repair (RCR) laterality. Hospitalizations were defined as any emergency department (ED) visit or hospital readmission within 90 days after primary ARCR. Surgeon-specific factors including surgeon case volume, career length, fellowship training, practice setting, and regional practice were analyzed in relation to postoperative outcomes using both univariate and multivariate logistic regression. Results: 94,150 patients underwent ARCR by 1489 surgeons. On multivariate analysis, high-volume surgeons demonstrated a higher risk for two-year total reoperation (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.01-1.12, P = .03) and revision RCR (OR = 1.06, 95% CI: 1.01-1.12, P = .02) compared to low-volume surgeons. Early-career surgeons showed higher rates of 90-day ED visits (mid-career surgeons: OR = 0.78, 95% CI: 0.73-0.83, P

Objective Aimed to evaluate patients with essential hypertension (EH) using four-dimensional automatic left atrial quantification (4DLAQ) To assess the occurrence of EH. Methods This study selected 80 patients with EH for the EH group and 36 healthy individuals for the control group. Various cardiac parameters, including left atrial diameter (LAD), interventricular septal thickness (IVST), left ventricular end-diastolic diameter (LVDD), left ventricular posterior wall thickness (LVPWT), early E-wave velocity of mitral valve diastole/mitral valve ring myocardial displacement velocity (E/e'), biplanar left ventricular ejection fraction (biplanLVEF), left atrial minimum volume (LAVmin), lateral left atrial maximum volume (LAVmax), left atrial presystolic volume (LAVpreA), left atrial ejection fraction obtained by two-dimensional echocardiography (LAEF), left atrial passive ejection fraction (LAPEF), left atrial active ejection fraction (LAAEF), left atrial reservoir longitudinal strain (LASr), left atrial catheter longitudinal strain (LAScd), left atrial systolic longitudinal strain (LASct), left atrial reservoir circular strain (LASr_c), left atrial catheter circular strain (LAScd_c), and left atrial systolic circular strain (LASct_c) were measured using 4DLAQ. Binary logistic regression was employed to analyze the effect of 4DLAQ strain parameters on EH. Receiver operating characteristic (ROC) curves were used to assess the predictive value of 4DLAQ strain parameters for EH. Results Systolic blood pressure and diastolic blood pressure in the EH group were higher than those in the control group (P = 0.000 and 0.000, respectively). In the EH group, LAD, IVST, LVDD, LVPWT, E/e', LAVmin, LAVmax, and LAVpreA were significantly increased (P = 0.000, 0.000, 0.072, 0.000, 0.000, 0.001, 0.052, and 0.004, respectively), whereas biplanLVEF, LAEF, LAPEF, LAAEF, LASr, LAScd, LASct, LASr_c, LAScd_c, and LASct_c significantly decreased (P = 0.090, 0.000, 0.009, 0.064, 0.000, 0.000, 0.000, 0.000, 0.000, and 0.689, respectively). Bland-Altman plots were used to illustrate the relationship between variables and audience consensus. LASr and LAScd were identified as independent risk factors for EH. The area under the ROC curve (AUC) for LASr was 0.925, (95% confidence interval [CI] = 0.879-0.971) with a sensitivity of 80.00%, specificity of 94.44%, using a cut-off value of 20%. For LAScd, the AUC-ROC was 0.878 (95% CI = 0.818-0.939 with a sensitivity of 76.25%, specificity 86.11%, and using a critical value of -11%. Conclusion LASr and LAScd exhibited superior predictive capabilities for EH, with LASr performing the best. This study fills a critical gap in left atrial research and holds significant clinical implications.

Objective: The study objective was to determine if intraoperative peritoneal catheter placement is associated with improved outcomes in neonates undergoing high-risk cardiac surgery with cardiopulmonary bypass. Methods: This propensity score–matched retrospective study used data from 22 academic pediatric cardiac intensive care units. Consecutive neonates undergoing Society of Thoracic Surgeons–European Association for Cardio-Thoracic Surgery category 3 to 5 cardiac surgery with cardiopulmonary bypass at centers participating in the NEonatal and Pediatric Heart Renal Outcomes Network collaborative were studied to determine the association of the use of an intraoperative placed peritoneal catheter for dialysis or passive drainage with clinical outcomes, including the duration of mechanical ventilation. Results: Among 1490 eligible neonates in the NEonatal and Pediatric Heart Renal Outcomes Network dataset, a propensity-matched analysis was used to compare 395 patients with peritoneal catheter placement with 628 patients without peritoneal catheter placement. Time to extubation and most clinical outcomes were similar. Postoperative length of stay was 5 days longer in the peritoneal catheter placement cohort (17 vs 22 days, P = .001). There was a 50% higher incidence of moderate to severe acute kidney injury in the no-peritoneal catheter cohort (12% vs 18%, P = .02). Subgroup analyses between specific treatments and in highest risk patients yielded similar associations. Conclusions: This study does not demonstrate improved outcomes among neonates with placement of a peritoneal catheter during cardiac surgery. Outcomes were similar apart from longer hospital stay in the peritoneal catheter cohort. The no-peritoneal catheter cohort had a 50% higher incidence of moderate to severe acute kidney injury (12% vs 18%). This analysis does not support indiscriminate peritoneal catheter use, although it may support the utility for postoperative fluid removal among neonates at risk for acute kidney injury. A multicenter controlled trial may better elucidate peritoneal catheter effects.

Objective: To reduce the frequency of insufficient overlap of intravenous (IV) and subcutaneous (SC) insulin during the treatment of diabetic ketoacidosis (DKA) as a quality improvement project. Patients and Methods: Rates of insufficient IV and SC insulin overlap (< 2-hour overlap, SC insulin given after IV insulin discontinuation, or no SC insulin given after IV insulin discontinuation) were assessed in adults with DKA treated with IV insulin at a large tertiary care referral center in Rochester, Minnesota, from July 1, 2021, to March 15, 2023. After a preintervention analysis period, an electronic medical record–based best practice advisory was introduced to notify hospital providers discontinuing IV insulin if SC long-acting insulin had not been given in the previous 2-6 hours. Demographic characteristics and clinical outcomes before and after intervention were compared. Results: A total of 352 patient encounters were included (251 in the preintervention phase and 101 in the postintervention phase). The rate of insufficient IV to SC insulin overlap decreased from (88 of 251) 35.1% before intervention to (20 of 101) 19.8% after intervention (P=.005). The rate of posttransition hypoglycemia (250 mg/dL), rebound DKA, length of hospital stay, and duration of IV insulin therapy were similar before and after intervention. Conclusion: Using quality improvement methodology, the rates of insufficient IV to SC insulin overlap during treatment of DKA in a large tertiary care referral center were measured and reduced through an electronic medical record–based best practice advisory targeting hospital providers.

Background: There is no consensus on optimal time points or systolic blood pressure (SBP) ranges for calculating SBP time in target range (TTR). Objectives: The purpose of this study was to examine the association between various SBP TTR metrics and long-term major adverse cardiovascular events (MACEs). Methods: This post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial) included participants with complete SBP records and excluded those with events in the initial 2 years. SBP TTR indices were calculated using 3 distinct time points and 3 SBP ranges. The SBP TTR index was the percentage of BP segments within the target SBP ranges. MACE, a composite of heart attack, stroke, heart failure, and cardiovascular death, was the primary outcome. Results: The study included 7,134 participants, of which 280 had a MACE. The median follow-up was 3.91 years. The SBP TTR 110-140 mm Hg in the initial 3 months (3-month TTR 110-140) had the optimal association with incident MACEs (HR per SD increase: 0.898 [95% CI: 0.788-1.022], relative informativeness = 24,398%). Furthermore, a cutoff value of 0.65 for 3-month TTR 110 to 140 index was identified by threshold saturation analysis and used to evaluate early SBP control. No difference in MACE was seen between different mean SBP subgroups in those with good early control (3-month TTR >0.65) (P = 0.88), but in those with poor early control (3-month TTR ≤0.65), a higher mean SBP of 130 to 140 mm Hg was related to increased MACEs risk (P = 0.019). Conclusions: In nondiabetic hypertensive patients, the 3-month TTR 110 to 140 mm Hg index was independently associated with 2-year MACEs. A cutoff of TTR index as 0.65 indicated that the patient was within BP target range 65% of the time, combined with mean SBP, could potentially be used as a metric for early control stability and late cardiovascular risks. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062)

Purpose: To investigate the safety and efficacy of intensity modulated carbon ion radiation therapy (IM-CIRT) using pencil beam scanning technology for patients with unresectable sacrococcygeal chordoma (SC). Methods and Materials: A total of 35 patients with unresectable SC were retrospectively analyzed, including 54.3% (19/35) recurrent cases. In 68.6% (24/35) cases, tumor was located in S2 or above, and all cases were treated with hypofractionated IM-CIRT. The median dose was 70.4 Gy (range, 69-80 Gy) (relative biologic effectiveness) in 16 fractions (range, 16-23 fractions), typically delivered over 5 fractions per week. Results: The 3-year overall survival, cause-specific survival, progression-free survival, locoregional progression–free survival, and distant metastasis–free survival rates with a median follow-up time of 42 months (range, 12-91 months) for the entire cohort were 93.2%, 96.3%, 61.8%, 80%, and 77.3%, respectively. Multivariate analysis revealed that gross tumor volume (hazard ratio, 3.807; 95% CI, 1.044-13.887; P = .043) was the only significant prognostic factor for progression-free survival and the dose for the gross tumor volume ≥70.4 Gy (relative biologic effectiveness) was relevant with significantly better locoregional progression–free survival (hazard ratio, 0.190; 95% CI, 0.038-0.940; P = .042). No significant prognostic factor for overall survival, cause-specific survival, and distant metastasis–free survival and no severe (ie, grade ≥3) acute toxicity were identified. Severe late toxicities occurred in 3 patients (8.57%): pain (1 patient), motor neuropathy (1 patient), and skin ulcer (1 patient). Furthermore, no severe toxicity related to urinary function or defecation was observed following IM-CIRT. Pain grades improved or remained unchanged in 85.7% of patients. Conclusions: IM-CIRT produced acceptable 3-year outcomes without substantial late adverse effects, especially urinary and anorectal complications for SC, and did not appear to increase pain. IM-CIRT at high doses using hypofractionated radiation therapy may improve outcomes for local control and seems to be feasible even for postoperative recurrent SC.

Background:. The occurrence of blindness resulting from facial injection is a catastrophic complication that remains a significant safety concern for patients. The aim was to assess public awareness of blindness caused by hyaluronic acid injection. Methods:. The Tencent questionnaire platform was used to gather self-reported demographic data, information about injection experience, and factors influencing the understanding of blindness. Additionally, we included an educational section on blindness caused by hyaluronic acid injection and evaluated the respondents’ intention to undergo injections. Results:. A total of 1000 respondents completed the questionnaire, 15.4% had received filler injections, and 53.7% expressed their consideration of facial filler injections. The majority of respondents (68.3%) reported being aware of the risk of blindness associated with filler injections, with professional health blogs, social media, and news serving as the primary sources of information. Furthermore, 93.4% of the respondents believed that plastic surgeons should discuss the risk of blindness with patients before injection. Conclusions:. The majority of the respondents in this study were aware of the possibility of blindness resulting from filler injections. Health blogs, news outlets, and social media platforms are likely the primary channels through which the public obtains information on this topic.

Patients with no-option chronic limb-threatening ischemia are not candidates for conventional revascularization options and will inevitably require major amputation. Deep venous arterialization (DVA) is a potential option for these patients. A complete endovascular system to perform DVA has recently received great acclaim and US Foor and Drug Administration approval. However, patients with severe tibial medial calcinosis such as those with diabetes or renal failure may not be candidates for this because most endovascular needles cannot penetrate severe calcium. Here we describe a novel hybrid approach to DVA that provided technical success in three patients with end-stage renal disease and severe medial calcinosis.

Background: Particulated autograft cartilage implantation is a surgical technique that has been previously described for the repair of osteochondral lesions of the talus (OLT). It uses cartilage fragments harvested from the OLT that are minced into 1-2-mm 3 fragments and then immediately reimplanted back into the chondral defect and sealed with fibrin glue during a single-stage surgery. The purpose of this study was to characterize the suitability of these minced cartilage fragments as immediate autograft for the treatment of OLTs. Methods: Thirty-one patients undergoing primary arthroscopic surgery for their OLT consented to have their loose or damaged cartilage fragments removed and analyzed in the laboratory. Harvested specimens were minced into 1- to 2-mm 3 fragments and cell count, cell density, and cell viability were determined. In addition, physical characteristics of the OLT lesion were recorded intraoperatively and analyzed including size, location, Outerbridge chondromalacia grade of the surrounding cartilage, density of underlying bone, and whether the surgeon thought the OLT was primarily hyaline or fibrocartilage. Results: An average of 419 000 cells was able to be obtained from the harvested OLT fragments. The cells were 71.2% viable after mincing. Specimens from younger patients and from lesions with worse chondromalacia adjacent to the OLT had significantly higher cell numbers. Those from lateral lesions and with worse neighboring chondromalacia had a significantly higher cell density. None of the remaining physical OLT characteristics studied seemed to significantly affect cell number or viability. Conclusion: A large number of viable cells are available for immediate autografting by removing the loose or damaged cartilage from an OLT and mincing it into 1- to 2-mm 3 fragments. These can be reimplanted into the chondral defect in a single-stage surgery. Future clinical studies are needed to determine if the addition of these live autologous cells either alone or in conjunction with other techniques significantly improves the quality of the repair tissue and clinical outcomes. Level of Evidence: Level IV, case series.

Anshen Dingzhi prescription (ADP) is a classic prescription of traditional Chinese medicine, which has been used in the treatment of neuropsychiatric diseases. However, its treatment of breast cancer-related post-traumatic stress disorder (BC-PTSD) lacks clinical research evidence and its mechanism is not clear. The present study investigated the efficacy and action mechanism of ADP against BC-PTSD. The results of the clinical trial showed that after 4 weeks of treatment, both groups showed reduced post-traumatic stress disorder checklist-civilian version (PCL-C), Pittsburgh sleep quality index (PSQI), self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores, and increased functional assessment of cancer therapy-breast (FACT-B) scores. The serum cortisol (CORT), tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) levels were decreased and brain-derived neurotrophic factor (BDNF) level were increased, and the improvement of serum TNF-α, IL-1β, and BDNF in treatment group was better than that of the control group. The overall treatment efficacy in the treatment group (43.90%) was superior to that in the control group (23.81%), and the overall incidence of adverse effects was lower than that in the control group. The results of network analysis and molecular docking showed that ADP blood components could act on IL1B, TNF, and BDNF. ADP contributes to the treatment of BC-PTSD symptoms, with a mechanism possibly related to its regulatory effect on TNF-α, IL-1β, and BDNF levels. Trial registration: Chinese Clinical Trial Registry, http://www.chictr.org.cn,ChiCTR2300077801

Background Rivaroxaban, a direct Factor Xa inhibitor, is commonly used for cerebral venous thrombosis (CVT) correction. However, pharmacokinetic differences in Chinese may vary in sensitivity and tolerance, resulting in either insufficient or excessive anticoagulation. Herein, the optimizing dosages of rivaroxaban in Chinese patients with CVT were analyzed based on monitoring anti-Xa activity dynamically, to maintain therapeutic efficacy and reduce rivaroxaban-related bleeding. Methods A real-world cohort study was conducted involving 112 CVT patients in Xuanwu Hospital, from August 2021 through January 2024. Patients were grouped according to their doses of rivaroxaban use (5, 10, 15, and 20 mg daily) based on dynamic plasma anti-Xa activity monitored using the chromogenic anti-Xa assay. Plasma levels of anti-Xa activity reached the therapeutic range, bleeding events and the dosage of rivaroxaban among these groups were analyzed. Results The ratios of the patients whose plasma anti-Xa levels reached the standard therapeutic level (0.3–0.7 IU/mL) between the cohorts less than 20 mg/d and 20 mg/d showed no statistical difference, and no significant disparities were observed among 5, 10, 15, and 20 mg/d dose groups. There was a discernible increase in the proportion of patients with bleeding events in the 20 mg/d group, even though the results did not reach a statistical difference. Meanwhile, in patients with bleeding events, their plasma anti-Xa levels could exceed 0.7 IU/mL. Conclusion Sensitivity and tolerance to rivaroxaban in Chinese may vary. Individualized therapy dosage under the guidance of anti-Xa activity monitoring may not only guarantee anticoagulation effect, but also reduce rivaroxaban-related bleeding events.

Background: In patients with metastatic colorectal cancer (mCRC), Quxie Cap-sule (QX)—a combination of conventional therapy (including chemotherapy, targeted therapy or supportive care)—has shown a significant overall survival benefit compared with placebo and might have the property of dual effects of antitumor and immunity enhancement, both mediated by the microbiome. In preclinical models, QX has also shown activity against colorectal cancer. This study aimed to describe how the aforementioned effects of QX look after when focusing on the patients in third or above line setting. Methods: A Simon’s Minimax two-stage phase II design was used in this study, which enrolled mCRC patients who progressed after second-line treatment. Patients received conventional therapy plus QX until disease progression or unacceptable toxicity. Before and after 1-month intervention, we collected patients’ stool samples for microbiome analysis by 16s rRNA sequencing approaches. And the microbiome analysis before and after 1-month intervention was done through bioinformation analysis platform. Results: Fifteen patients were enrolled and gut microbiome were analyzed from 7 of 10 patients that with PFS over 3.7 months. Microbiome community analysis on genus level showed that the proportion of Lachnospiraceae_UCG-001 (0.04% vs 1.06%, P = .02249) significantly increased after conventional therapy plus QX while the proportion of Alistipes (2.96% vs 1.35%, P = .03461), Flavonifractor (0.04% vs 0.02%, P = .02249), Bifidobacterium (6.11% vs 1.14%, P = .02249) and Butyricimonas (0.24% vs 0.11%, P = .03603) significantly decreased after intervention . LEfSe analysis showed that after intervention, samples were highly related with unclassified-f-lachnospiraceae , Eubacterium and Lachnospiraceae_UCG-001 . Conclusions: Decrease of gut bacteria with potential roles in carcinogenesis of colorectal cancer and increase in the abundance of gut anticancer bacteria such as Lachnospiraceae may partly explain how conventional therapy combined with QX can influence carcinogenesis and tumor progression in colon cancer. Trial registration: Chinese Clinical Trial Registry (ChiCTR2100053874).

Introduction: Responses to first-line programmed cell death protein 1 inhibition vary among patients with metastatic NSCLC and a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) greater than or equal to 50%. We previously reported improved clinical outcomes to first-line programmed cell death protein 1 inhibition in patients with metastatic NSCLC with a PD-L1 TPS of greater than or equal to 90% versus 50% to 89% in a pilot study. Here, we report the three-year survival with first-line pembrolizumab and cemiplimab in two large independent cohorts of patients with PD-L1 TPS greater than or equal to 90% versus 50% to 89% and characterize genomic and immunophenotypic differences between these PD-L1 expression groups, which were largely unknown. Methods: We analyzed three-year outcomes of the following two independent cohorts: (1) a multicenter cohort of patients from four academic centers in the United States treated with pembrolizumab and (2) EMPOWER-Lung 1, randomized, phase III trial comparing first-line cemiplimab with chemotherapy. Tumor genomic profiling and multiplexed immunofluorescence were performed to evaluate genomic and immunophenotypic correlates of very high PD-L1 expression. Results: At three years of follow-up, progression-free survival (hazard ratio [HR], 0.69; p < 0.001) and overall survival (HR, 0.70; p < 0.01) to first-line commercial pembrolizumab were significantly improved in patients with a PD-L1 TPS greater than or equal to 90% versus 50% to 89%. In the EMPOWER-Lung 1, patients assigned to the cemiplimab arm with a PD-L1 TPS greater than or equal to 90% also had significant improvements in progression-free survival (HR, 0.53; p < 0.0001) and overall survival (HR, 0.63; p = 0.007) compared with those with a PD-L1 of 50% to 89%. Tumor genomic profiling of 553 NSCLC samples revealed that mutations in STK11 and SMARCA4 were significantly more frequent in tumors with a PD-L1 TPS of 50% to 89% compared with those with a PD-L1 TPS greater than or equal to 90% (Q < 0.15), whereas BRCA2 was enriched in NSCLC samples with a PD-L1 TPS greater than or equal to 90% (Q < 0.15). Multiplexed immunofluorescence on 93 NSCLC samples identified higher intratumoral CD8+PD1+ T cells (p = 0.02) in tumors with PD-L1 TPS greater than or equal to 90% versus 50% to 89%. Conclusion: Pembrolizumab and cemiplimab were found to have long-term survival benefit and favorable genomic and immunophenotypic profile in patients with advanced NSCLC with PD-L1 TPS greater than or equal to 90% compared with TPS 50% to 89%.

Objectives Surgery is the mainstream treatment for early-stage esophageal squamous cell carcinoma (ESCC) and occult recurrent laryngeal nerve lymph node metastasis (RLNM) is not uncommon among those with R0 resection. The clinical value of postoperative radiotherapy (PORT) in patients with RLNM only is still controversial. Methods Consecutive patients with early-stage ESCC treated with R0 resection and pathologically confirmed RLNM only from June 2012 to July 2022 were retrospectively reviewed. PORT, covering the supraclavicular and superior mediastinum area (small T-field) at a dose of 50.4 Gy for 28 fractions, was performed in some patients. Propensity score matching (PSM) was performed to balance the baseline characteristics between patients with or without PORT. Pattern of failure, disease-free survival (DFS), and overall survival (OS) were compared. Results Among the 189 patients identified, 69 (35.5%) received PORT and the other 120 (63.5%) did not. After PSM, 154 patients were included in the matched cohort, including 62 in the PORT group and 92 in the non-PORT group. With a median follow-up of 48 (95% CI: 40.3-55.7) months, 69 patients developed their initial disease recurrence in the whole population and PORT significantly decreased the frequency of local recurrence (61.2% vs 21.4%) among those with recurrent disease. Additionally, in the PSM matched cohort, PORT significantly prolonged patients’ DFS (HR 0.393, P = 0.002) and OS (HR 0.462, P = 0.020). Moreover, PORT remained as the independent factor associated with improved DFS (HR 0.360, P = 0.001) and OS (HR 0.451, P = 0.021) after multivariate Cox analyses. In addition, tumor location and pathological TNM stage were found to be independent prognostic factors associated with survival outcomes. Conclusion PORT is associated with improved DFS and OS in ESCC patients with R0 resection and RLNM only, which warrants future validation.

Communication is a core component of a clinician’s role; however, when clinicians conduct research, communicating the emerging findings and recommendations to different types of stakeholders can be unfamiliar territory. Communicating research to advocate for change can be even more challenging. Clinician researchers seeking to be agents for change need to conceive and craft specific, evidence-based messages and communicate these effectively to different stakeholders to negotiate action. As part of a global health research program, we developed and tested a novel game-based model to strengthen the communication skills of clinician researchers, from 4 countries, for improving services for chronic obstructive pulmonary disease. This model focused on communication with 3 key stakeholder groups for knowledge translation: Patients/carers, healthcare providers and policy makers/healthcare managers. Delivered through a series of facilitated, online meetings, this model consisted of 2 parts: developing and rehearsing advocacy messages with coaching support, and then testing them with a panel of 3 representative stakeholders, and an audience of fellow researchers. All the country teams reported increased confidence in crafting advocacy messages for specific stakeholders and have applied lessons learned from the model. Delivering this model within a global health research program requires mentoring, time, commitment, resources and translation support to address language barriers. It offers an exemplar to build the communication skills of clinician and non-clinician researchers so that they can go beyond dissemination toward translation of evidence into policy and practice.

Background Recently, the effect of Lipoprotein(a) [Lp(a)] on thrombogenesis has aroused great interest, while inflammation has been reported to modify the Lp(a)-associated risks through an unidentified mechanism. Purpose This study aimed to evaluate the association between platelet reactivity with Lp(a) and high-sensitivity C-reactive protein (hs-CRP) levels in percutaneous intervention (PCI) patients treated with clopidogrel. Methods Data were collected from 10,724 consecutive PCI patients throughout the year 2013 in Fuwai Hospital. High on-treatment platelet reactivity (HTPR) and low on-treatment platelet reactivity (LTPR) were defined as thrombelastography (TEG) maximum amplitude of adenosine diphosphate-induced platelet (MA ADP ) > 47 mm and

Background Currently, no universally accepted standardized VTE risk assessment model (RAM) is specifically designed for critically ill patients. Although the ICU-venous thromboembolism (ICU-VTE) RAM was initially developed in 2020, it lacks prospective external validation. Objectives To evaluate the predictive performance of the ICU-VTE RAM in terms of VTE occurrence in mixed medical-surgical ICU patients. Methods We prospectively enrolled adult patients in the ICU. The ICU-VTE score and Caprini or Padua score were calculated at admission, and the incidence of in-hospital VTE was investigated. The performance of the ICU-VTE RAM was evaluated and compared with that of Caprini or Padua RAM using the receiver operating curve. Results We included 269 patients (median age: 70 years; 62.5% male). Eighty-three (30.9%) patients experienced inpatient VTE. The AUC of the ICU-VTE RAM was 0.743 (95% CI, 0.682-0.804, P

Background. Combined heart liver transplant (CHLT) continues to gain attention as a surgical treatment for patients with end-stage heart and liver disease but remains rare. We present our institutional longitudinal experience with up to 14 y of follow-up, focused on long-term outcomes in CHLT recipients. Methods. We conducted a single-institutional, retrospective review from January 1, 2010, to December 31, 2023, including 7 patients ages 7–17 y who underwent CHLT. Results. Most patients were surgically palliated via Fontan procedure pretransplant (n = 6), and all had evidence of advanced fibrosis or cirrhosis before transplant. The 30-d mortality was 14.3% (n = 1, multiorgan failure). During the follow-up period, 1 patient developed acute heart rejection which required treatment and 2 developed acute liver rejection. In all cases, rejection was successfully treated. Two patients developed acute heart rejection which did not require treatment (grade 1R). No patients developed chronic or refractory rejection. No patients developed allograft coronary artery vasculopathy. Conclusions. CHLT remains a rarely performed treatment for pediatric patients with end-stage heart and liver disease, but our long-term data suggest that this treatment strategy should be considered more frequently.

Allergic rhinitis (AR) and urticaria affect a sizable portion of the population worldwide, resulting in reduced quality-of-life and productivity and increased healthcare costs.Fexofenadine (FEX) is a non-sedating second-generation H1 antihistamine with pronounced efficacy and a very good safety profile, used for the treatment of allergic diseases. In addition to its antihistaminic properties, FEX also has anti-inflammatory effects. FEX has a wide therapeutic window and is not associated with any sedative effects, even at higher than recommended doses.There is a need for an integrated management system for AR and urticaria which includes safe and effective treatment options.An ideal anti-allergic formulation should provide fast relief of symptoms and long-lasting effect without drowsiness. Data from randomized clinical trials show that FEX meets these criteria and is an effective treatment option with a favourable safety profile, improving the quality of life of patients suffering from AR and urticaria.

Background: Underprescribing of guideline-directed medical therapy (GDMT) for heart failure (HF) persists. Objectives: The purpose of this study was to assess polypharmacy as a barrier to GDMT. Methods: We examined participants hospitalized for HF with reduced ejection fraction and HF with mildly reduced ejection fraction between 2003 and 2017 from the Reasons for Geographic and Racial Differences in Stroke study. Participants were stratified by admission medication count—0 to 4, 5 to 9, and ≥10 medications. We examined GDMT use at admission, GDMT contraindications, and initiation of eligible indicated GDMT by medication count. We conducted a multivariable Poisson regression with robust standard errors to examine the association between medication count and GDMT initiation. GDMT included agents for HF with reduced ejection fraction/HF with mildly reduced ejection fraction, antiplatelet agents and statins for coronary artery disease, and anticoagulants for atrial fibrillation. Results: Among 545 participants with HF, 34% were not taking a beta-blocker, 39% were not taking an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, or hydralazine-isosorbide dinitrate, and 90% were not taking a mineralocorticoid receptor antagonist at admission; among participants with coronary artery disease, 36% were not taking an antiplatelet agent, and 38% were not taking a statin; and among participants with atrial fibrillation, 49% were not taking an anticoagulant. Polypharmacy was inversely associated with initiation of at least one indicated medication (5-9 medications: relative risk [RR]: 0.67; 95% CI: 0.56-0.82; P

Background: Allergic rhinitis (AR) is a typical type 2 inflammatory disease and eosinophils play a critical role of cardinal effectors in type 2 inflammation. However, the distribution of eosinophils in patients with different subtypes of rhinitis and the effect of allergen exposure on them remain understudied. The aim of this study was to investigate the characteristics and factors influencing the distribution of systemic and local eosinophils in patients with non-AR (NAR), perennial AR (PAR), and seasonal AR (SAR), as well as the effect of seasonal allergen exposure levels on eosinophils. Methods: This was a population-based, cross-sectional observational study of consecutive chronic rhinitis (CR) outpatients who volunteered to participate in the survey during the spring pollen season and non-pollen season of 2023 in Beijing. All participants underwent serum allergen testing, blood routine examination, and nasal secretion smear cytology, and completed questionnaires mainly involving basic information, history review, and symptom assessment. Spring pollen dispersal concentration were considered. Results: A total of 558 CR patients eligible for enrollment were collected, including 198 NAR, 204 PAR, and 156 SAR patients. PAR had the highest blood eosinophil levels and the most severe overall nasal and ocular symptoms of SAR. Compared with subjects with blood eosinophil counts

Background Previous studies have established a positive correlation between serum uric acid to creatinine (SUA/Cr) ratio and cardiovascular disease, but the relationship between SUA/Cr ratio and the prognosis of heart failure (HF) remains unknown. This study investigated the potential of SUA/Cr ratio as a prognostic predictor for patients with HF. Methods This single-center prospective cohort study enrolled 2,122 patients with HF between March 2013 and June 2017. All patients were divided into 3 groups according to SUA/Cr ratio tertiles and were followed up with until December 31, 2022. The association between SUA/Cr ratio and the prognosis of HF was assessed using the Cox proportional hazards model. Results The mean (SD) age and mean (SD) SUA/Cr ratio of the study cohort (66% male) were 59.3 (14.7) years and 4.71 (2.09), respectively. During a median follow-up period of 15 months (range, 11-26 months), 390 end-point events were observed. Prognosis analysis revealed that a high SUA/Cr ratio was associated with an increased mortality risk of HF (hazard ratio, 1.62 [95% CI, 1.26-2.09]; P < .001) compared with the SUA/Cr ratio in the lowest tertile. After adjusting for covariates, the hazard ratio for mortality risk of HF was 1.71 (95% CI, 1.23-2.37; P = .001). Subgroup analysis showed that mortality risk increased in direct proportion with the SUA/Cr ratio in female patients, patients with a history of hypertension and β-blocker use, and patients with UA levels below 428 μmol/L and creatinine levels less than 97 mg/dL. Stratification by age; by history of diabetes, hyperlipidemia, and smoking; and by level of fasting plasma glucose, however, had no obvious effect on the association between SUA/Cr ratio and HF prognosis. Patients with higher SUA/Cr ratios had reduced left ventricular ejection fraction and increased left ventricular end-diastolic diameter. Conclusion A high SUA/Cr ratio was an independent risk factor for the mortality risk of HF.

Objective To investigate the effectiveness of SMI in evaluating hepatic IRI and detecting its therapy response. Methods Thirty rats were randomly divided into sham (n = 12), IRI (n = 12), and andrographolide pretreatment (n = 6) groups. SMI, pathological, and biochemical examinations were conducted for the sham and IRI groups at 4 (n = 6) and 24 h (n = 6) after reperfusion, respectively. Two ultrasonologists measured the vascular index (VI). The interobserver agreement was evaluated using the intraclass correlation coefficient (ICC). The rat liver parameters, including Suzuki's score, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), were obtained at different time steps in each group. For the andrographolide pretreatment group, data were obtained at 24 h after reperfusion to further verify the advantage of VI. Parameters were analyzed for correlations and compared between each group at 4 and 24 h. Results The ICC between two ultrasonologists who measured the VI was 0.912 (95%CI: 0.889-0.940). Suzuki's score and VI were negatively correlated (r = -0.504, P = 0.012). Compared with the sham group, the IRI group showed a significant decrease in the VI at 4 and 24 h after reperfusion [(24.78 ± 3.23) versus (20.22 ± 2.55); (22.67 ± 1.36) versus (19.27 ± 2.23), P < 0.05)]. The VI in the andrographolide pretreatment group was higher than that in the IRI group [(21.90 ± 1.47) versus (19.27 ± 2.23), P

Objective: Challenges persist in surgery for neonatal total anomalous pulmonary venous connection (neoTAPVC), with the high mortality risk not mitigated over time. Methods: A prospectively collected single-center database containing all neonates with TAPVC undergoing biventricular repair in 2012 to 2020 was retrospectively reviewed. The primary outcome was death or postoperative pulmonary venous obstruction (PPVO). Based on the preoperative admission location in our hospital, patients were classified into those being admitted to cardiac intensive care unit versus neonatal intensive care unit or general pediatric intensive care unit. Access to dedicated presurgical care (DPC) was defined as patients who were preoperatively admitted to the cardiac intensive care unit. Results: Overall, 241 patients with a median age at surgery of 14 days (interquartile range [IQR], 9-21 days) were included. Anomalous return was supracardiac in 38.6%, cardiac in 26.1%, infracardiac in 28.6%, and mixed in 6.6%. Patients receiving DPC had better survival (96.3% vs 84.3%; P = .0028) and lower incidence of PPVO (15.2% vs 28.6%; P = .011) compared with those without DPC. Patients in the DPC group were less likely to undergo operation within 24 hours on presentation (27.1% vs 40.3%; P = .041), had improved lactate clearance (1.5 [IQR, 1.0-2.2] vs 2.8 [IQR, 1.8-4.1]; P

Torrential bleeding is a rare and life-threatening complication of arteriovenous malformations (AVMs). We report a case of head and neck AVMs present with uncontrollable torrential bleeding, which was treated with embolization and sclerotherapy. Then we explored the potential multidisciplinary handling of the procedure for this kind of case. A 25-year-old female patient was born with right face and head AVMs. The AVMs had grown gradually and ruptured spontaneously with uncontrollable torrential bleeding before admission. Emergent direct hemostasis, nasotracheal intubation, and staged embolization and sclerotherapy were carried out on this patient. Finally, the bleeding stopped and the wound healed successfully. Embolization and sclerotherapy are effective for head and neck AVMs with uncontrollable torrential bleeding. Multidisciplinary collaboration is needed to achieve a good outcome.

Background Breast cancer is a prevalent public health concern affecting numerous women globally and is associated with palmitoylation, a post-translational protein modification. Despite increasing focus on palmitoylation, its specific implications for breast cancer prognosis remain unclear. The work aimed to identify prognostic factors linked to palmitoylation in breast cancer and assess its effectiveness in predicting responses to chemotherapy and immunotherapy. Methods We utilized the “limma” package to analyze the differential expression of palmitoylation-related genes between breast cancer and normal tissues. Hub genes were identified using the “WGCNA” package. Using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis, we identified a prognostic feature associated with palmitoylation and developed a prognostic nomogram with the “regplot” package. The predictive values of the model for chemotherapy and immunotherapy responses were assessed using immunophenoscore (IPS) and the “pRophetic” package. Results We identified 211 differentially expressed genes related to palmitoylation, among which 44 demonstrated prognostic potential. Subsequently, a predictive model comprising eleven palmitoylation-related genes was developed. Patients were classified into high-risk and low-risk groups based on the median risk score. The findings revealed that individuals in the high-risk group exhibited lower survival rates, while those in the low-risk group showed increased immune cell infiltration and improved responses to chemotherapy and immunotherapy. Moreover, the BC-Palmitoylation Tool website was established. Conclusion This study developed the first machine learning-based predictive model for palmitoylation-related genes and created a corresponding website, providing clinicians with a valuable tool to improve patient outcomes.

Detect the expression of Farnesoid X Receptor(FXR), Multiple Drug Resistance Associated Protein-1(MRP-1) and Solute Carrier Family 7, Member 5 (SLC7A5) in hepatocellular carcinoma(HCC) of rat model, so as to provide new therapeutic targets for gene therapy of HCC. Sixty male Wistar rats were randomly divided into three groups. The rats in experimental group were given 0.2% diethylnitrosamine (DEN) by gavage with a dose of 10 mg/kg, 3 times a week, and it stopped at 12 weeks. The control group rats were given physiological saline by gavage, while the sham operation group did not receive anything by gavage. At 10 weeks, one rat in the experimental group was euthanized, and the changes of livers were recorded. The procedure was repeated at 12 weeks. After 12 weeks, HCC only occurred in the experimental group. After confirming the formation of the tumor through pathological examination, liver tissues and tumor tissues were taken from the three groups. FXR, MRP-1 and SLC7A5 expression in liver tissues and tumor tissues was detected. After 7 weeks the rats in experimental group ate less, and their weight was significantly reduced. Three months later, HCC was detected in 15 rats in the experimental group. The ratio of FXR/GAPDH mRNA, MRP-1/GAPDH mRNA, SLC7A5/GAPDH mRNA were significantly different among the three groups. Under the light microscope the FXR protein, MRP-1 protein, and SLC7A5 protein react with their respective antibodies, and they showed granular expression. Every pathological section included different numbers of positive cells in each group. FXR expression in HCC of rats was significantly lower than that in normal liver tissues, but MRP-1 and SLC7A5 expression in HCC were significantly higher than that in normal liver tissues, suggesting that drugs targeting FXR, MRP-1 and SLC7A5 may be new strategies for the treatment of HCC.

Lung cancer is the most prevalent and lethal malignant tumor in China, primarily categorized into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC accounts for more than 80% of all lung cancer cases, with current treatments primarily consisting of surgery, chemotherapy, and targeted therapy. However, these treatments often come with various adverse effects and drug resistance issues, highlighting the urgent need for new NSCLC therapies. Traditional Chinese medicine serves as a natural treasury of medicinal compounds and an important avenue for discovering novel active compounds. Platycodin D (PD) is a triterpenoid saponin isolated from the roots of Platycodon, possessing various pharmacological properties. Nevertheless, the exact mechanism of PD’s anti-lung cancer activity remains unclear. In this study, 3 lung cancer cell models, A549, NCI-H1299, and PC-9, were employed. After intervention with Platycodin-D, tumor cell proliferation and migration were assessed. Cell migration ability was assessed through transwell assays, while transcriptomics was employed to explore the mechanism of PD’s anticancer activity. Bioinformatic analysis revealed significant enrichment of apoptosis and the TGFβ pathway following PD intervention, as shown in gene expression heatmaps, where genes associated with cancer were significantly downregulated by PD intervention. Subsequently, we used immunofluorescent labeling of KI-67 to evaluate cell proliferation, flow cytometry to assess apoptosis, and Western blot to detect protein expression of TGFβ and P-SMAD3. Immunofluorescence was also employed to investigate E-cadherin, vimentin, and N-cadherin. Finally, molecular docking and dynamic simulations were utilized to study the interaction between PD and TGFβ proteins. The results of this study indicate that PD exhibits robust anti-lung cancer pharmacological activity, with its primary target being TGFβ. PD may serve as a potential TGFβ inhibitor and a candidate drug for NSCLC treatment.

Summary:. Calvarial reconstruction of complex frontal bone defects after head trauma surgery is challenging, especially when it coexists with an absence of eyebrow arch and supraorbital wall. Due to various reasons, the patient’s bone flap could not be used. Common alternative materials include polyetheretherketone (PEEK) and titanium. Careful and detailed planning is required to maximize functional and aesthetic reconstruction, thereby benefiting the patient. We present a case of a 36-year-old man who had multiple frontal bone defects after multiple operations for craniofacial fractures performed with reconstruction surgery using a PEEK implant successfully. With a follow-up for 2 years, the patient was satisfied with the long-term aesthetic effect without any consequences such as surrounding tissue infection or implant displacement. The authors believe that the PEEK implant has great potential for calvarial reconstruction due to its incredible strength, durability, and inertness.

To investigate the status quo and influencing factors of overall frailty and its 3 domains among rural community-dwelling older adults. This is a cross-sectional study. A convenience sample of 195 older adults from 6 villages in Bashang Area of Zhangjiakou City, Hebei Province, China, were recruited from August to September, 2022. The demographic characteristics, the Chinese version of Tilburg Frailty Indicator, Charlson Comorbidity Scale and Hospital Anxiety and Depression Scale were used to investigate frailty and its influencing factors. Univariate analysis and multiple linear regression analysis were employed. The prevalence of overall frailty among the older adults in Bashang Area was 85.13%. Multiple linear regression analysis showed that age, gender, marital status, regular exercise, comorbidity, and anxiety were the influencing factors of overall frailty. While anxiety was the only shared influencing factor for physical frailty, psychological frailty, and social frailty, age, gender, marital status, financial burden, the comorbidity, and regular exercise were factors which influenced 1 or 2 domains of frailty. The prevalence of overall frailty among the older adults in rural areas, Zhangjiakou City is high. It is influenced by many factors. Medical staff and policy makers should work hand in hand to improve frailty among rural community-dwelling older adults in China.

Background: To evaluate the efficacy and safety of allogenic CD8 + natural killer T (CD8+ NKT) immunotherapy combined with gefitinib in the treatment of advanced or metastatic EGFR mutant non-small cell lung cancer (NSCLC). Methods: This study is prospective. The NSCLC patients with exon 19 (Ex19del) or exon 21 L858R point mutations, and response to gefitinib treatment were enrolled into the trial to be randomly assigned into the gefitinib arm and the gefitinib/NKT arm. Allogenic CD8+ NKT cells were cultured in vitro and adaptive transferred into the patients via vein in the gefitinib/NKT arm. The primary endpoint was progression-free survival (PFS). Secondary endpoint analysis included time to disease progression (TTP), overall survival (OS), levels of serum tumour markers for carcinoembryonic antigen (CEA) and alanine aminotransferase (ALT) in the blood, the response rate and safety. From July 2017 to June 2021, 19 patients were randomly assigned to the gefitinib arm (n = 8) and the gefitinib/NKT arm (n = 11). Results: The estimated median survival PFS in the gefitinib/NKT arm was significantly longer than that of the gefitinib arm (12 months vs 7 months). Similar results were also observed for the median TTP. Moreover, the gefitinib/NKT arm had better CEA control than the gefitinib arm. Clinical grade 3 adverse reactions occurred in 64% and 39% of patients in the gefitinib/NKT arm and the gefitinib arm, respectively. The most common grade 3 adverse events in the gefitinib/NKT arm included abnormal liver function in 8 cases (73%) and diarrhoea in 1 case (9%), both of which resolved after drug intervention. Conclusion: The PFS of EGFR-mutated advanced NSCLC treated with allogenic CD8+ NKT cells combined with gefitinib was longer than that of gefitinib alone. No obvious serious adverse reactions occurred, and the patients compliance and survival status were good.

Background Patients with frailty are more prone to have perioperative adverse events, and enhanced recovery after surgery (ERAS) has been widely adopted to improve perioperative outcomes. The purpose of this study was to assess the impact of improved compliance with ERAS on perioperative outcomes in frail patients. Methods Geriatric patients (over 65 years) who underwent multi-level lumbar fusion surgery between June 2017 and June 2022 were included. The patients were divided into two groups according to their degree of compliance with the ERAS. Stepwise nearest-neighbor propensity score matching 1:1 cohorts for age, gender, body mass index (BMI), American Society of Anesthesiologists (ASA) classfication and Charlson Comorbidity Index (CCI) was performed between groups, namely frail-compliant (FC), frail-noncompliant (FN). Further length of stay (LOS), complications and clinical efficacy were compared between groups. Results There were 83 pairs of well-balanced patients with comparable clinical baseline data. It was worth noting that patients in FC group has significant lower overall complications (20.5% in the FC group vs 39.8% in the FN group, P = 0.007), major complications (7.2% in the FC group vs 19.3% in the FN group, P = 0.022) and shorter LOS (11.18 ± 5.32 in the FC group vs 14.45 ± 4.68 in the FN group, P < 0.001) than patients in FN group. In addition, the initial occurrence of ambulation (2.14 ± 1.21 in FC group vs 3.18 ± 1.73 in FN group, P = 0.012) and bowel movement (3.68 ± 1.24 in FC group vs 4.17 ± 1.32 in FN group, P = 0.031) were earlier for patients in FC group than patients in FN group. With regard to clinical efficacy, there were no significant difference between FC and FN group in terms of patients who meet minimal clinical important difference (MCID) for Oswestry Disability Index (ODI) at postoperative day (POD) 30, Visual Analog Scale (VAS) for back at POD 30-90 and VAS for legs at POD 30, 90, and 180 follow-up intervals. However, there were significant more patients meeting MCID for ODI at POD 90 and180, and VAS for back at POD 180 between FC and FN group. Conclusions In this retrospective cohort study, we found that frail patients with higher ERAS adherence group had a lower incidence of overall complication, mjor complications, and a shorter LOS than their lower ERAS adherence counterparts. In addition, frail patients with higher ERAS adherence had earlier ambulatioin and bowel movement. More importantly, we found there were significant more patients meeting MCID for ODI at POD 90 and180, and VAS for back at POD 180 in higher ERAS adherence than their lower counterparts.

Introduction and objectives The present study aimed to investigate different peripheral lymphocyte subsets in patients with severe hemophilia A (HA) and factor VIII (FVIII) inhibitor production. For this, age-matched cases of 19 FVIII inhibitor-positive (IP), 21 FVIII inhibitor-negative (IN) and 45 healthy controls were selected for study. Methods Flow cytometry was used to analyze the peripheral lymphocyte subsets, including T, B, natural killer (NK) and NKT cells. The T cell subsets included CD3 + CD4-CD8- [double negative T (DNT)], CD3 + CD4 + CD8+ [double-positive T (DPT)], CD3 + CD4 + CD8- and CD3 + CD4-CD8+ T cells. Pairwise comparisons of absolute lymphocyte subset values were conducted among the three groups. The cut-off value for absolute lymphocyte counts was determined using receiver operating characteristic curve analysis. Results The results demonstrated that the absolute values of DPT cells in the IN and IP groups were significantly lower than those in the healthy control group ( P = 0.007). The DNT values were also lower in severe HA patients with or without inhibitor than those in healthy subjects, but these differences were not statistically significant ( P = 0.053). In addition, the absolute value of CD4+ Th cells in the IP group was lower than that in the healthy controls ( P = 0.013). Although not statistically significant ( P = 0.064), the absolute values of NKT cells were higher in the IN group compared with the IP group, and higher in the IP group compared with the healthy control group. There were no statistically significant differences in total T, B, CD8 + and NK cells among the IN, IP and healthy control groups. The cut-off value for absolute CD4+ Th cells in the IN group was 598/µl, clinicians should be vigilant for possible FVIII inhibitor production, especially on days prior to FVIII exposure.

Purpose Research on bone metastasis in esophageal cancer (EC) is relatively limited. Once bone metastasis occurs in patients, their prognosis is poor, and it severely affects their quality of life. Currently, there is a lack of convenient tumor markers for early identification of bone metastasis in EC. Our research aims to explore whether neutrophil-lymphocyte ratio (NLR) can predict bone metastasis in patients with EC. Methods Retrospective analysis of clinical indicators was performed on 604 patients with EC. They were divided into groups based on whether or not there was bone metastasis, and the patients’ coagulation-related tests, blood routine, tumor markers and other indicators were collected. The receiver operating characteristic curve (ROC) were used to determine the predictive ability of parameters such as NLR for bone metastasis in EC, and univariate and multivariate logistic regression analyses were conducted to determine the impact of each indicator on bone metastasis. Using binary logistic regression to obtain the predictive probability of NLR combined with tumor markers. Results ROC curves analysis suggested that the area under the curve (AUC) of the NLR was 0.681, with a sensitivity of 79.2% and a specificity of 52.6%, which can be used as a predictive factor for bone metastasis in EC. Multivariate logistic regression analysis showed that high NLR (odds ratio [OR]: 2.608, 95% confidence interval [CI]: 1.395-4.874, P = 0.003) can function as an independent risk factor for bone metastasis in patients with EC. Additionally, high PT, high APTT, high FDP, high CEA, high CA724, low hemoglobin, and low platelet levels can also predict bone metastasis in EC. When NLR was combined with tumor markers, the area under the curve was 0.760 (95% CI: 0.713-0.807, P

Introduction: In recent years, the development of drug-eluting embolization beads that can be imaged has become a hot research topic in regard to meeting clinical needs. In our previous study, we successfully developed nano-assembled microspheres (NAMs) for multimodal imaging purposes. NAMs can not only be visualized under CT/MR/Raman imaging but can also load clinically required doses of doxorubicin. It is important to systematically compare the pharmacokinetics of NAMs with those of commercially available DC Beads and CalliSpheres to evaluate the clinical application potential of NAMs. Methods: In our study, we compared NAMs with two types of drug-eluting beads (DEBs) in terms of irinotecan, drug-loading capacity, release profiles, microsphere diameter variation, and morphological characteristics. Results: Our results indicate that NAMs had an irinotecan loading capacity similar to those of DC Beads and CalliSpheres but exhibited better sustained release in vitro. Conclusion: NAMs have great potential for application in transcatheter arterial chemoembolization for the treatment of colorectal cancer liver metastases.

This study explored 1-year follow-up of Parmaco-invasive strategy with half-dose recombinant human prourokinase (PHDP) in patients with acute ST-segment elevation myocardial infarction (STEMI). The follow-up endpoints were major adverse cardiovascular events (MACEs) occurring within 30 days and 1 year, as well as postoperative bleeding events. The study ultimately included 150 subjects, with 75 in the primary percutaneous coronary intervention (PPCI) group and 75 in the PHDP group. This study found that the PHDP group had a shorter FMC-reperfusion time (42.00 min vs 96.00 min, P 0.05). The PHDP facilitates early treatment of infarct-related vessels, shortens FMC-reperfusion time, and does not increase the risk of MACEs.