Logistic regression analysis of risk factors influencing childhood enuresis: a comprehensive survey study.

OBJECTIVE: To identify risk factors associated with childhood enuresis. METHODS: We conducted a retrospective analysis of 146 children aged 6 to 13 years diagnosed with enuresis at Anhui Province Children's Hospital between June 2020 and June 2023. Children were categorized based on bedwetting frequency: those with less frequent episodes (once a week to twice a month) were placed in the mild group (60 cases), and those with frequent episodes (two or more times per week) were placed in the severe group (86 cases). We compared demographic data, family histories, and personal characteristics between the groups and performed logistic regression to determine significant risk factors. RESULTS: The analysis revealed that a stubborn personality, nocturnal polyuria, sleep-wake disorders, and bladder dysfunction significantly increased the risk of enuresis (P < 0.05). These findings underscore the importance of a holistic approach in evaluating psychological aspects, nocturnal urination patterns, sleep quality, and bladder health in managing enuresis. CONCLUSION: The study identifies stubborn personality, nocturnal polyuria, sleep-wake disorders, and bladder dysfunction as independent risk factors for childhood enuresis. Understanding these factors is crucial for developing targeted interventions that can enhance the management and outcomes of enuresis. Future research should explore the interrelationships among these factors to refine preventive and therapeutic strategies for early childhood enuresis.

Intermittent lysis on a single paper-based device to extract exosomal nucleic acid biomarkers from biological samples for downstream analysis.

As the role of exosomes in physiological and pathological processes has been properly perceived, harvesting them and their internal components is critical for subsequent applications. This study is a debut of intermittent lysis, which has been integrated into a simple and easy-to-operate procedure on a single paper-based device to extract exosomal nucleic acid biomarkers for downstream analysis. Exosomes from biological samples were captured by anti-CD63-modified papers before being intermittently lysed by high-temperature, short-time treatment with double-distilled water to release their internal components. Exosomal nucleic acids were finally adsorbed by sol-gel silica for downstream analysis. Empirical trials not only revealed that sporadically dropping 95 °C ddH2O onto the anti-CD63-modified papers every 5 min for 6 times optimized the exosomal nucleic acids extracted by the anti-CD63 paper but also verified that the whole deployed procedure is applicable for point-of-care testing (POCT) in low-resource areas and for both in vitro (culture media) and in vivo (plasma and chronic lesion) samples. Importantly, downstream analysis of exosomal miR-21 extracted by the paper-based procedure integrated with this novel technique discovered that the content of exosomal miR-21 in chronic lesions related to their stages and the levels of exosomal carcinoembryonic antigen originated from colorectal cancer cells correlated to their exosomal miR-21.

Evaluation of a novel vaginal cells self-sampling device for human papillomavirus testing in cervical cancer screening: A clinical trial assessing reliability and acceptability.

Cervical cancer is a significant public health concern, particularly in low- and middle-income countries where resources for prevention and treatment are limited. Routine screening, such as the Papanicolaou test (Pap smears) and human papillomavirus (HPV) testing, plays a crucial role in the early detection and prevention of cervical cancer. However, the participation rate in cervical cancer screening programs remains below optimal levels due to various factors. This study aimed to evaluate the reliability and acceptability of the HygeiaTouch Self Sampling Kit for Women in collecting vaginal samples for HPV typing, comparing the results with samples collected by physicians. The study included 1210 women aged 21-65 from three medical centers in Taiwan. The findings indicated that the self-sampling kit was as effective as physician-collected specimens in terms of obtaining valid samples and identifying HPV. The agreement between the two methods was 88%, with a κ value of 0.75. Furthermore, the study assessed the mechanical characteristics of the self-sampling applicator through tensile, bending, and torque tests, and determined that it was safe for intravaginal use. Additionally, the study evaluated the safety and satisfaction of self-sampling and found a low rate of adverse events (0.7%) and high levels of satisfaction (over 90%) among participants. Overall, we demonstrated that the HygeiaTouch Self Sampling Kit for Women is a reliable and acceptable device for HPV testing and cervical screening, providing a convenient, safe, and effective alternative for women.

Risk Factors and Predictive Nomogram for Survival in Elderly Patients with Brain Glioma.

OBJECTIVE: To determine the factors that contribute to the survival of elderly individuals diagnosed with brain glioma and develop a prognostic nomogram. METHODS: Data from elderly individuals (age ≥65 years) histologically diagnosed with brain glioma were sourced from the Surveillance, Epidemiology, and End Results (SEER) database. The dataset was randomly divided into a training cohort and an internal validation cohort at a 6:4 ratio. Additionally, data obtained from Tangdu Hospital constituted an external validation cohort for the study. The identification of independent prognostic factors was achieved through the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis, enabling the construction of a nomogram. Model performance was evaluated using C-index, ROC curves, calibration plot and decision curve analysis (DCA). RESULTS: A cohort of 20 483 elderly glioma patients was selected from the SEER database. Five prognostic factors (age, marital status, histological type, stage, and treatment) were found to significantly impact overall survival (OS) and cancer-specific survival (CSS), with tumor location emerging as a sixth variable independently linked to CSS. Subsequently, nomogram models were developed to predict the probabilities of survival at 6, 12, and 24 months. The assessment findings from the validation queue indicate a that the model exhibited strong performance. CONCLUSION: Our nomograms serve as valuable prognostic tools for assessing the survival probability of elderly glioma patients. They can potentially assist in risk stratification and clinical decision-making.

Fluorescence-based reagent and spectrum-based optical reader for lactoferrin detection in tears: differentiating Sjögren's syndrome from non-Sjögren's dry eye syndrome.

Identification of an early biomarker and effective testing device to differentiate dry eye disease secondary to autoimmune disease (Sjögren's syndrome dry eye disease) from non-Sjögren's dry eye disease are prerequisites for appropriate treatment. We aimed to demonstrate the capacity of a new photo-detection device to evaluate tear lactoferrin levels as a tool for differentiating systemic conditions associated with dry eye disease. Patients with non-Sjögren's and Sjögren's syndrome dry eye disease (n = 54 and n = 52, respectively) and controls (n = 11) were enrolled. All participants completed the Ocular Surface Disease Index questionnaire. Tear collection was performed with Schirmer test, and tear break-up time was examined using a slit lamp. Tear lactoferrin was evaluated using our newly developed photo-detection device. The average lactoferrin concentration was significantly lower in samples from patients with non-Sjögren's dry eye disease (0.337 ± 0.227 mg/mL, n = 54) and Sjögren's syndrome dry eye disease (0.087 ± 0.010 mg/mL, n = 52) than in control samples (1.272 ± 0.54 mg/mL, n = 11) (p < 0.0001). Further, lactoferrin levels were lower in patients with Sjögren's syndrome dry eye disease than in those with non-Sjögren's dry eye disease (p < 0.001). Our cost-effective, antibody-free, highly sensitive photo-detection device for evaluating tear lactoferrin levels can assist ophthalmologists in differentiating different types of dry eye diseases.

A retrospective study of uropathogen and its antibiotic resistance among children with urinary tract infection from a single center in China.

Urinary tract infection (UTI) is a well-known bacterial infection posing serious health problem in children. A retrospective study was conducted to explore the uropathogen and its antibiotic resistance in children with UTI. Data of urine culture and antimicrobial susceptibility test was collected. Consequently, 840 children were included. The overall culture-positive UTI was 458 (54.52 %) with Escherichia coli 166 (36.24 %), followed by Enterococcus faecalis 59 (12.88 %), Enterococcus faecium 70 (15.28 %) and others. They were highly resistant to the most commonly used antibiotics. In 694 children with complicated UTI, there were 8 children with fungal infection. Multiple drug resistance (MDR) was recorded in 315 (80.98 %). The overall proportion of Extended Spectrum ß-Lactamase (ESßL) production was 25 (6.43 %). In 146 children with simple UTI, MDR were also detected in 47 (77.05 %). There were 6 (9.84 %) positive for ESßL production. Our study found that complicated UTI was relatively common. Escherichia coli was the most prevalent isolate, followed by Enterococcus faecium and Enterococcus faecalis. These organisms were highly resistant to the most commonly used antibiotics. Relatively high prevalence of MDR and low ESßL-producing organisms were observed.

The Force-Frequency Characteristics of Quartz Wafers under a Cantilever Beam Structure.

This study investigated the force-frequency characteristics of quartz wafers inside a cantilever beam frame. Firstly, the force-frequency coefficient formula of quartz wafers with fixed ends under axial force was analyzed. Firstly, the formula for the force-frequency coefficient of quartz wafers with fixed ends under axial force was analyzed. A force-frequency coefficient formula suitable for cantilever beam structures was derived by considering the changes in surface stress and stiffness of quartz wafers with fixed ends and one end under force on the other. Subsequently, the formula's accuracy was verified by experiments, and the accuracy was more than 92%. In addition, strain simulation analysis was performed on three different shapes of quartz wafers, and experimental verification was carried out on two of them. The results revealed that trapezoidal quartz wafers and cantilever beam structures exhibited superior stress distribution to rectangular chips. Furthermore, by positioning electrodes at various locations on the surface of the quartz chip, it was observed that, as the electrodes moved closer to the fixed end, the force-frequency coefficient of the rectangular quartz chip increased, along with an increase in chip strain under the cantilever structure. In summary, this study provides a new approach for designing cantilever quartz resonator sensors in the future.

Unilateral boundary time series forecasting.

Time series forecasting is an essential tool across numerous domains, yet traditional models often falter when faced with unilateral boundary conditions, where data is systematically overestimated or underestimated. This paper introduces a novel approach to the task of unilateral boundary time series forecasting. Our research bridges the gap in existing methods by proposing a specialized framework to accurately forecast within these skewed datasets. The cornerstone of our approach is the unilateral mean square error (UMSE), an asymmetric loss function that strategically addresses underestimation biases in training data, improving the precision of forecasts. We further enhance model performance through the implementation of a dual model structure that processes underestimated and accurately estimated data points separately, allowing for a nuanced analysis of the data trends. Additionally, feature reconstruction is employed to recapture obscured dynamics, ensuring a comprehensive understanding of the data. We demonstrate the effectiveness of our methods through extensive experimentation with LightGBM and GRU models across diverse datasets, showcasing superior accuracy and robustness in comparison to traditional models and existing methods. Our findings not only validate the efficacy of our approach but also reveal its model-independence and broad applicability. This work lays the groundwork for future research in this domain, opening new avenues for sophisticated analytical models in various industries where precise time series forecasting is crucial.

COVID-19 Vaccination in Pregnancy: Pilot Study of Plasma MicroRNAs Associated with Inflammatory Cytokines after COVID-19 mRNA Vaccination.

BACKGROUND: The impact of mRNA COVID-19 vaccines on the immunological profiles of pregnant women remains a crucial area of study. This research aims to explore the specific immunological changes triggered by these vaccines in this demographic. METHODS: In a focused investigation, we examined the effects of mRNA COVID-19 vaccination on microRNA expression in pregnant women. Key microRNAs, including miR-451a, miR-23a-3p, and miR-21-5p, were analyzed for expression changes post-vaccination. Additionally, we assessed variations in S1RBD IgG levels and specific cytokines to gauge the broader immunological response. RESULTS: Post-vaccination, significant expression shifts in the targeted microRNAs were observed. Alongside these changes, we noted alterations in S1RBD IgG and various cytokines, indicating an adapted inflammatory response. Notably, these immunological markers displayed no direct correlation with S1RBD IgG concentrations, suggesting a complex interaction between the vaccine and the immune system in pregnant women. CONCLUSIONS: Our pilot study provides valuable insights into the nuanced effects of the mRNA COVID-19 vaccine on immune dynamics in pregnant women, particularly emphasizing the role of microRNAs. The findings illuminate the intricate interplay between vaccines, microRNAs, and immune responses, enhancing our understanding of these relationships in the context of pregnancy. This research contributes significantly to the growing body of knowledge regarding mRNA COVID-19 vaccines and their specific impact on maternal immunology, offering a foundation for further studies in this vital area.

In silico identification of a novel Cdc2-like kinase 2 (CLK2) inhibitor in triple negative breast cancer.

Dysregulation of RNA splicing processes is intricately linked to tumorigenesis in various cancers, especially breast cancer. Cdc2-like kinase 2 (CLK2), an oncogenic RNA-splicing kinase pivotal in breast cancer, plays a significant role, particularly in the context of triple-negative breast cancer (TNBC), a subtype marked by substantial medical challenges due to its low survival rates. In this study, we employed a structure-based virtual screening (SBVS) method to identify potential CLK2 inhibitors with novel chemical structures for treating TNBC. Compound 670551 emerged as a novel CLK2 inhibitor with a 50% inhibitory concentration (IC50) value of 619.7 nM. Importantly, Compound 670551 exhibited high selectivity for CLK2 over other protein kinases. Functionally, this compound significantly reduced the survival and proliferation of TNBC cells. Results from a cell-based assay demonstrated that this inhibitor led to a decrease in RNA splicing proteins, such as SRSF4 and SRSF6, resulting in cell apoptosis. In summary, we identified a novel CLK2 inhibitor as a promising potential treatment for TNBC therapy.

Monocyte chemoattractant protein-1 detection in wound tissue fluids for the assisted diagnosis of wound infection.

BACKGROUND: Infections are commonly seen in wounds. The overall infection rate is 1.8% to 4.2%. Improper infection management can lead to serious conditions and may progress to life-threatening sepsis. Because there is a need for assistance in predicting wound infection before obvious clinical symptoms, the measurement of cytokines in wound tissue fluids has attracted our attention for determining the overall status of wound infection. Our intent was to assess the potential biomarkers in the diagnosis of wound infection. METHODS: We collected 146 tissue fluids (acute: 59, chronic: 61, and normal: 26) for analysis of biomarkers using a human cytokine array. Serum C-reactive protein was also measured from 104 patients. The sensitivity and specificity of significant wound cytokines and serum C-reactive protein for the diagnosis of wound infection were evaluated. RESULTS: Among biomarkers examined, serum C-reactive protein and tissue C-reactive protein were highly expressed in acute infection wounds, whereas monocyte chemoattractant protein-1 was significantly expressed in chronic infection wounds. Because the expression of wound biomarkers varied in different types of wounds, relationships among them were studied. A high correlation between tissue C-reactive protein and interleukin-8 (R2 = 0.7) and a moderate correlation between systemic and local C-reactive protein (R2 = 0.47) were observed. In addition, tissue monocyte chemoattractant protein-1 had better sensitivity (74%) and specificity (65%) in the diagnosis of wound infection. Moreover, combined serum C-reactive protein with monocyte chemoattractant protein-1 examination provided a higher area under the curve in the receiver operator characteristic curve (0.75). CONCLUSION: We found that tissue monocyte chemoattractant protein-1 is a superior diagnostic marker for assistance with the diagnosis of wound infection.

TRAIL and IP-10 dynamics in pregnant women post COVID-19 vaccination: associations with neutralizing antibody potency.

Introduction: The aim of this study is to investigate changes in TNF-related apoptosis-inducing ligand (TRAIL) and gamma interferon-induced protein 10 (IP-10) after COVID-19 vaccination in pregnant women and to explore their association with neutralizing antibody (Nab) inhibition. Methods: The study evaluated 93 pregnant women who had previously received two (n=21), three (n=55) or four (n=17) doses of COVID-19 vaccine. Also we evaluated maternal blood samples that were collected during childbirth. The levels of TRAIL, IP-10 and Nab inhibition were measured using enzyme-linked immunosorbent assays (ELISA). Results and discussion: Our study revealed four-dose group resulted in lower TRAIL levels when compared to the two-dose and three-dose groups (4.78 vs. 16.07 vs. 21.61 pg/ml, p = 0.014). The two-dose group had reduced IP-10 levels than the three-dose cohort (111.49 vs. 147.89 pg/ml, p=0.013), with no significant variation compared to the four-dose group. In addition, the four-dose group showed stronger Nab inhibition against specific strains (BA.2 and BA.5) than the three-dose group. A positive correlation was observed between TRAIL and IP-10 in the two-dose group, while this relationship was not found in other dose groups or between TRAIL/IP-10 and Nab inhibition. As the doses of the COVID-19 vaccine increase, the levels of TRAIL and IP-10 generally increase, only by the fourth dose, the group previously vaccinated with AZD1222 showed lower TRAIL but higher IP-10. Despite these changes, more doses of the vaccine consistently reinforced Nab inhibition, apparently without any relation to TRAIL and IP-10 levels. The variation may indicate the induction of immunological memory in vaccinated mothers, which justifies further research in the future.

Exploring the Implementation of Shared Decision-Making Involving Health Coaches for Diabetes and Hypertension Self-Management: Qualitative Study.

BACKGROUND: An emerging focus on person-centered care has prompted the need to understand how shared decision-making (SDM) and health coaching could support self-management of diabetes and hypertension. OBJECTIVE: This study aims to explore preferences for the scope of involvement of health coaches and health care professionals (HCPs) in SDM and the factors that may influence optimal implementation of SDM from the perspectives of patients and HCPs. METHODS: We conducted focus group discussions with 39 patients with diabetes and hypertension and 45 HCPs involved in their care. The main topics discussed included the roles of health coaches and HCPs in self-management, views toward health coaching and SDM, and factors that should be considered for optimal implementation of SDM that involves health coaches. All focus group discussions were audio recorded, transcribed verbatim, and analyzed using thematic analysis. RESULTS: Participants agreed that the main responsibility of HCPs should be identifying the patient's stage of change and medication education, while health coaches should focus on lifestyle education, monitoring, and motivational conversation. The health coach was seen to be more effective in engaging patients in lifestyle education and designing goal management plans as health coaches have more time available to spend with patients. The importance of a health coach's personal attributes (eg, sufficient knowledge of both medical and psychosocial management of disease conditions) and credentials (eg, openness, patience, and empathy) was commonly emphasized. Participants viewed that addressing the following five elements would be necessary for the optimal implementation of SDM: (1) target population (newly diagnosed and less stable patients), (2) commitment of all stakeholders (discrepancy on targeted times and modality), (3) continuity of care (familiar faces), (4) philosophy of care (person-centered communication), and (5) faces of legitimacy (physician as the ultimate authority). CONCLUSIONS: The findings shed light on the appropriate roles of health coaches vis-à-vis HCPs in SDM as perceived by patients and HCPs. Findings from this study also contribute to the understanding of SDM on self-management strategies for patients with diabetes and hypertension and highlight potential opportunities for integrating health coaches into the routine care process.

Left Upper Extremity Pain, Right Coronary Artery Culprit: A Puzzling Path to Aneurysm Discovery.

Giant coronary artery aneurysm (GCA) is a rare disease afflicting 0.2% of the population. It is primarily attributed to atherosclerosis in adults and Kawasaki disease in children. Other uncommon etiologies include Takayasu arteritis and post-percutaneous coronary intervention.1,2 GCA lacks a universally accepted definition, with proposed criteria including a diameter exceeding 2 cm, 5 cm, or four times the normal vessel size.3 While the majority of GCAs are asymptomatic, a subset of patients present with angina, myocardial infarction from embolization or compression, heart failure due to fistula formation, or even sudden death.1 We report a case of an adult harboring a GCA involving the right coronary artery.

Acceptability of Mobile App-Based Motivational Interviewing and Preferences for App Features to Support Self-Management in Patients With Type 2 Diabetes: Qualitative Study.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) experience multiple barriers to improving self-management. Evidence suggests that motivational interviewing (MI), a patient-centered communication method, can address patient barriers and promote healthy behavior. Despite the value of MI, existing MI studies predominantly used face-to-face or phone-based interventions. With the growing adoption of smartphones, automated MI techniques powered by artificial intelligence on mobile devices may offer effective motivational support to patients with T2DM. OBJECTIVE: This study aimed to explore the perspectives of patients with T2DM on the acceptability of app-based MI in routine health care and collect their feedback on specific MI module features to inform our future intervention. METHODS: We conducted semistructured interviews with patients with T2DM, recruited from public primary care clinics. All interviews were audio recorded and transcribed verbatim. Thematic analysis was conducted using NVivo. RESULTS: In total, 33 patients with T2DM participated in the study. Participants saw MI as a mental reminder to increase motivation and a complementary care model conducive to self-reflection and behavior change. Yet, there was a sense of reluctance, mainly stemming from potential compromise of autonomy in self-care by the introduction of MI. Some participants felt confident in their ability to manage conditions independently, while others reported already making changes and preferred self-management at their own pace. Compared with in-person MI, app-based MI was viewed as offering a more relaxed atmosphere for open sharing without being judged by health care providers. However, participants questioned the lack of human touch, which could potentially undermine a patient-provider therapeutic relationship. To sustain motivation, participants suggested more features of an ongoing supportive nature such as the visualization of milestones, gamified challenges and incremental rewards according to achievements, tailored multimedia resources based on goals, and conversational tools that are interactive and empathic. CONCLUSIONS: Our findings suggest the need for a hybrid model of intervention involving both app-based automated MI and human coaching. Patient feedback on specific app features will be incorporated into the module development and tested in a randomized controlled trial.

Pilot Study on Evaluating the Impact of Tetanus, Diphtheria, and Pertussis (Tdap), Influenza, and COVID-19 Vaccinations on Antibody Responses in Pregnant Women.

This study assessed IgG levels to influenza/pertussis and neutralizing antibody (Nab) responses of COVID-19 vaccines in blood of pregnant women following immunization with pertussis (Tdap), influenza, and COVID-19 vaccines. We prospectively collected 71 participants categorized by the following vaccine combinations: 3TI, 4TI, 3T, and 4T groups (three and four doses of COVID-19 vaccines plus Tdap/influenza or Tdap vaccines alone). Our findings have indicated that the 3TI group exhibited elevated IgG levels for influenza B compared to the 3T group (12.90 vs. 7.75 U, p = 0.001); this pattern was not observed for influenza A. Pertussis IgG levels remained uniform across all groups. The 4TI group demonstrated a greater Nab inhibition rate from COVID-19 vaccines compared to both the 3TI and 3T groups (61.34% vs. 22.5% and 15.16%, respectively, p = 0.001). We observed no correlation between Nab inhibition rate and IgG levels for Tdap/influenza, with the exception of a moderate correlation with influenza B in the 3TI group. The efficacy of Tdap vaccine in pregnant women remained consistent, regardless of the administration of COVID-19 or influenza vaccines. Interestingly, without the influenza vaccine, both three and four doses of the COVID-19 vaccine still offered protection against influenza A, but not B. Hence, co-administering COVID-19, influenza, and Tdap vaccines during prenatal care maintains immunogenicity and is highly advised to safeguard pregnant women fully.

Lung Ultrasound Score as a Predictor of Failure to Wean COVID-19 Elderly Patients off Mechanical Ventilation: A Prospective Observational Study.

Background: The lung ultrasound score was developed for rapidly assessing the extent of lung ventilation, and it can predict failure to wean various types of patients off mechanical ventilation. Whether it is also effective for COVID-19 patients is unclear. Methods: This single-center, prospective, observational study was conducted to assess the ability of the 12-region lung ultrasound score to predict failure to wean COVID-19 patients off ventilation. In parallel, we assessed whether right hemidiaphragmatic excursion or previously published predictors of weaning failure can apply to these patients. Predictive ability was assessed in terms of the area under the receiver operating characteristic curve (AUC). Results: The mean age of the 35 patients in the study was (75 ± 9) years and 12 patients (37%) could not be weaned off mechanical ventilation. The lung ultrasound score predicted these failures with an AUC of 0.885 (95% CI 0.770-0.999, p < 0.001), and a threshold score of 10 provided specificity of 72.7% and sensitivity of 92.3%. AUCs were lower for previously published predictors of weaning failure, and right hemidiaphragmatic excursion did not differ significantly between the two groups. Conclusion: The lung ultrasound score can accurately predict failure to wean critically ill COVID-19 patients off mechanical ventilation, whereas assessment of right hemidiaphragmatic excursion does not appear helpful in this regard. Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05706441.

Transarterial Chemoembolization with Epirubicin-Loaded Microspheres for Hepatocellular Carcinoma: A Prospective, Single-Arm, Multicenter, Phase 2 Study (STOPPER Trial).

PURPOSE: While the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 µm) microspheres loaded with epirubicin. MATERIALS AND METHODS: This prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30-50), 75 (range, 60-90), or 100 (range, 75-125) µm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events. RESULTS: Data from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere (n = 9), epirubicin (n = 9), or procedure (n = 12) with none resulting in death. CONCLUSION: DEB-TACE using epirubicin-loaded small-sized (≤ 100 µm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC. TRIAL REGISTRATION: Clinicaltrials.gov NCT03113955; registered April 14, 2017. Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017. LEVEL OF EVIDENCE: 2, Prospective, Non-randomized, Single-arm, study.

Efficacy and safety of neoadjuvant sintilimab in combination with FLOT chemotherapy in patients with HER2-negative locally advanced gastric or gastroesophageal junction adenocarcinoma: an investigator-initiated, single-arm, open-label, phase II study.

BACKGROUND: The addition of immune checkpoint inhibitors to neoadjuvant chemotherapy in operable advanced gastric or gastroesophageal junction (G/GEJ) cancer aroused wide interest. This study was designed to assess the efficacy and safety of neoadjuvant sintilimab, a programmed cell death protein-1 (PD-1) inhibitor, in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy for HER2-negative locally advanced G/GEJ cancer. METHODS: Eligible patients with clinical stage cT4 and/or cN+M0 G/GEJ cancer were enroled in this phase II study. Patients received neoadjuvant sintilimab (200 mg every 3 weeks) for three cycles plus FLOT (50 mg/m 2 docetaxel, 80 mg/m 2 oxaliplatin, 200 mg/m 2 calcium levofolinate, 2600 mg/m 2 5-fluorouracil every 2 weeks) for four cycles before surgery, followed by four cycles of adjuvant FLOT with same dosages after resection. The primary endpoint was the pathological complete response (pCR) rate. RESULTS: Thirty-two patients were enroled between August 2019 and September 2021, with a median follow-up of 34.8 (95% CI, 32.8-42.9) months. Thirty-two (100%) patients received neoadjuvant therapy, and 29 underwent surgery with an R0 resection rate of 93.1%. The pCR (TRG0) was achieved in 5 (17.2%; 95% CI, 5.8-35.8%) patients, and the major pathological response was 55.2%. Twenty-three (79.3%) patients had T downstaging, 21 (72.4%) had N downstaging, and 19 (65.5%) had overall TNM downstaging. Six (20.7%) patients experienced recurrence. Patients achieving pCR showed better event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) than non-pCR. The estimated 3-year EFS rate, 3-year DFS rate, and 3-year OS rate were 71.4% (95% CI, 57.2-89.2%), 78.8% (95% CI, 65.1-95.5%), and 70.9% (95% CI, 54.8-91.6%), respectively. The objective response rate and disease control rate were 84.4% (95% CI, 68.3-93.1%) and 96.9% (95% CI, 84.3-99.5%), respectively. Twenty-five (86.2%) received adjuvant therapy. The main grade ≥3 treatment-related adverse events (TRAEs) were lymphopenia (34.4%), neutropenia (28.1%), and leukopenia (15.6%). no patients died from TRAE. The LDH level exhibited a better predictive value to pathological responses than PD-L1 and MSI status. CONCLUSIONS: The study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant sintilimab plus FLOT in HER2-negative locally advanced G/GEJ cancer, which suggested a potential therapeutic option for this population.

Combined analysis of transcriptomics and metabolomics provide insights into the antibacterial mechanism of bacteriocin XJS01 against multidrug-resistant Staphylococcus aureus.

Multidrug-resistant (MDR) bacteria are widespread in the environment and pose a serious threat to public health. It has been shown that bacteriocins have a great potential in controlling MDR pathogens, including Staphylococcus aureus. A previously reported Lactobacillus salivarius bacteriocin XJS01 exhibited good antibacterial activity against MDR S. aureus 2612:1606BL1486 (henceforth referred to as S. aureus_26), but its molecular mechanism remains unknown. Herein, we investigated the antibacterial mechanism of XJS01 on S. aureus_26 using an approach combining transcriptomics and metabolomics. The results showed that XJS01 induced significant changes at both transcriptional and metabolic levels in S. aureus_26. In total, 231 differentially expressed genes (DEGs) and 206 differentially abundance metabolites (DAMs) were identified in S. aureus_26 treated with 1 × MIC (minimum inhibition concentration) XJS01 compared with untreated (XJS01-free) cells (control). Functional analysis revealed that these DEGs and DAMs, alone with the related pathways and biological processes, were typically involved in stress response, being primarily related to metal uptake, cell virulence, self-help mechanism, amino acid and energy metabolism, bacterial stress response (e.g., two-component system), and membrane transport (e.g., phosphotransferase system). Overall, this study uncovered the multi-target effects of bacteriocins against MDR S. aureus at the genome-wide transcriptional and metabolic levels. These findings might be useful in the development of bacteriocins for the control of MDR S. aureus and other drug-resistant bacteria.