Clinical Effectiveness and Safety of Dupilumab in Chronic Obstructive Pulmonary Disease Patients: A 7-Year Population-based Cohort Study.

BACKGROUND: Previous randomized controlled trials had established the efficacy of dupilumab among patients with chronic obstructive pulmonary disease (COPD) treated with triple therapy over 52 weeks of follow-up. OBJECTIVE: This population-based cohort study aimed to explore the long-term clinical effectiveness of dupilumab in COPD patients. METHODS: This population-based cohort study included U.S. patients with COPD between April 2017 and August 2024. Patients initiating dupilumab and therapies that incorporated long-acting ß2-agonists (LABA) inhalers were included. Patients with asthma or lung cancer were excluded. The risk of outcomes after the initiation of dupilumab versus LABA-containing therapies was measured. For detailed Methods, please see the Methods section in this article's Online Repository at www.jacionline.org. RESULTS: A total of 1,521 dupilumab initiators and 1,521 propensity score-matched patients receiving LABA-based therapies were included. Dupilumab recipients were associated with lower all-cause mortality (HR:0.53, 95% CI:0.43-0.65), emergency visits (HR:0.78, 95% CI:0.69-0.89), and acute exacerbation (AE) rates (HR:0.59, 95% CI:0.53-0.65). Dupilumab was also associated with reductions in the requirement of short-acting ß2-agonists (HR:0.48, 95% CI:0.43-0.52), short-acting muscarinic antagonists (HR:0.43, 95% CI:0.37-0.49) for symptoms control. Additionally, dupilumab decreased subsequent pneumonia (HR:0.65, 95% CI:0.50-0.86), and COPD-relevant comorbidities including new-onset heart failure (HR:0.69, 95% CI:0.53-0.90) and new-onset anxiety (HR:0.70, 95% CI:0.53-0.93). CONCLUSIONS: Dupilumab was associated with a lower rate of mortality, emergency visits, reduced risk of AEs, respiratory symptoms, and respiratory infections in COPD patients. More studies are required to validate the effectiveness of dupilumab among patients with COPD across various severities.

Correction: Outcomes of lumen apposing metal stent placement in patients with surgically altered anatomy: Multicenter international experience.

[This corrects the article DOI: 10.1055/a-2411-1814.].

Insufficient Effective Time of Suberanilohydroxamic Acid, a Deacetylase Inhibitor, Treatment Promotes PC3 Cell Growth.

Castration-resistant prostate cancer (CRPC) contributes mostly to prostate cancer-specific mortality, and conventional castration therapy is almost ineffective, new therapies are needed. As a new potential anti-cancer drug, histone deacetylases (HDACs) inhibitors were demonstrated to be effective in inhibiting drug-resistance cancers in preclinical studies, but the results from clinical trials on CRPC patients were disappointing, and the reasons are unknown. In this study, we investigated the effect of suberanilohydroxamic acid (SAHA), a broad-spectrum pan-HDAC inhibitor, on proliferation, apoptosis, cell cycle progression in PC3 cells, and found that, unlike significant inhibiting effects at high-dose, low-dose SAHA significantly promoted PC3 cell growth. Further colony formation assay showed that the inhibitory effect of SAHA is also dependent on the treatment time, high-dose SAHA also exhibited promoting effect on PC3 cells when the treatment time was insufficient. However, this effect was not observed in another CRPC cell line, DU145, or another HDAC inhibitor, Trichostatin A (TSA). Our results indicate that, instead of inhibitory effect, SAHA would promote PC3 cell growth if the dose is low or the treatment time is insufficient, but this effect has not been observed in other CRPC cell line or HDAC inhibitors.

Outcomes of lumen apposing metal stent placement in patients with surgically altered anatomy: Multicenter international experience.

Background and study aims Although outcomes of lumen-apposing metal stents (LAMS) placement in native anatomy have been reported, data on LAMS placement in surgically altered anatomy (SAA) are sparse. We aimed to assess outcomes of LAMS placement in patients with SAA for different indications. Patients and methods This was an international, multicenter, retrospective, observational study at 25 tertiary care centers through November 2023. Consecutive patients with SAA who underwent LAMS placement were included. The primary outcome was technical success defined as correct placement of LAMS. Secondary outcomes were clinical success and safety. Results Two hundred and seventy patients (125 males; average age 61 ± 15 years) underwent LAMS placement with SAA. Procedures included EUS-directed transgastric ERCP (EDGE) and EUS-directed transenteric ERCP (EDEE) (n = 82), EUS-guided entero-enterostomy (n = 81), EUS-guided biliary drainage (n = 57), EUS-guided drainage of peri-pancreatic fluid collections (n = 48), and EUS-guided pancreaticogastrostomy (n = 2). Most cases utilized AXIOS stents (n = 255) compared with SPAXUS stents (n = 15). Overall, technical success was 98%, clinical success was 97%, and the adverse event (AE) rate was 12%. Using AGREE classification, five events were rated as Grade II, 21 events as Grade IIIa, and six events as IIIb. No difference in AEs were noted among stent types ( P = 0.52). Conclusions This study shows that placement of LAMS is associated with high technical and clinical success rates in patients with SAA. However, the rate of AEs is noteworthy, and thus, these procedures should be performed by expert endoscopists at tertiary centers.

Salidroside prevents cadmium chloride-induced DNA damage in human fetal lung fibroblasts.

BACKGROUND: Cadmium (Cd) is an environmental pollutant and a heavy metal known for its genotoxic effects, which can lead to cancer and other related diseases. Preventing Cd-induced genotoxicity is crucial; however, there is limited research on this topic. Salidroside (SAL), a phenylpropanoid glycoside isolated from Rhodiola rosea L., is a popular medicinal compound with several health benefits. Nevertheless, its therapeutic effect on Cd-induced genotoxicity remains unexplored. METHODS: Human fetal lung fibroblasts were treated with 20 µM Cd2+ (CdCl2) for 12 h and 5-20 µM SAL was used to test the anti-DNA damage effect. DNA damage was evaluated using γH2AX expression and the alkaline comet assay. Intracellular reactive oxygen species (ROS) levels were measured using flow cytometry. RESULTS: Exposure to 20 µM Cd2+ for 12 h induced significant DNA damage in human fetal lung fibroblasts, and this effect was notably attenuated by SAL treatment. SAL treatment did not decrease ROS levels in cells treated with Cd2+. CONCLUSION: SAL effectively prevented Cd2+-induced DNA damage in human fetal lung fibroblasts. However, the underlying mechanism requires further investigation.

Ultra-processed foods intake and sex hormone levels among children and adolescents aged 6-19 years: a cross-sectional study.

Background: Sex hormones are crucial for the development of children and adolescents. The increasing consumption of ultra-processed foods (UPFs) among children and adolescents in the United States (US) has raised concerns about their potential impact on health, including hormonal balance. Methods: Data from 3,354 participants aged 6-19 years from the NHANES 2013-2016 were analyzed. UPF intake was categorized using the NOVA food classification system, and the percentage of total daily energy intake from UPFs was calculated. The serum levels of total testosterone (TT), sex hormone-binding globulin (SHBG), and estradiol (E2) were measured. The free androgen index (FAI) and TT/E2 ratio were calculated to estimate bioavailable testosterone levels and the balance between androgens and estrogens, respectively. Multiple linear regression models, adjusted for potential confounders, estimated the associations. Results: Our results showed that higher intake of UPFs was marginally associated with decreased serum SHBG levels (quartile (Q) 2 vs. Q1: ß = -5.3, 95% confidence interval (CI): -17.0, 8.1%; Q3 vs. Q1: ß = -14.6, 95%CI: -25.1, -2.5%; Q4 vs. Q1: ß = -9.0, 95%CI: -20.3, 3.8%; P trend = 0.081), and significantly associated with increased serum FAI in female adolescents (Q2 vs. Q1: ß = 3.2, 95%CI: -3.3, 9.7; Q3 vs. Q1: ß = 7.6, 95%CI: -0.7, 16.0; Q4 vs. Q1: ß = 9.5, 95%CI: 1.5, 17.6; P trend = 0.019). Additionally, UPF intake showed a marginally positive association with increased serum SHBG levels (P trend = 0.057) in male children and FAI (P trend = 0.150) in male adolescents, respectively. Similar results were observed when participants were stratified by puberty status, except for the association between UPF intake and SHBG in male children. However, there were no associations between UPF consumption and TT, E2, or the TT/E2 ratio, both in males and females. Conclusion: Higher UPF consumption is associated with increased FAI in adolescents, particularly in girls, indicating higher bioavailable testosterone levels. Future studies should validate these findings with direct free testosterone measurements and more precise dietary intake assessments.

Comparative Analysis of Ketorolac and Parecoxib for Postoperative Pain Management in Uvulopalatopharyngoplasty.

Background/Objectives: Uvulopalatopharyngoplasty (UPPP) is a prevalent surgical procedure for treating obstructive sleep apnea. Effective postoperative pain management is crucial for patient comfort and recovery. This study aimed to compare the analgesic efficacies of parecoxib and ketorolac in patients undergoing UPPP. Methods: A prospective, randomized, double-blind study was conducted on 83 patients who received either parecoxib (40 mg intravenously every 12 h) or ketorolac (30 mg intravenously every 8 h) for 2 days following UPPP. Postoperative pain and swallowing discomfort were assessed using visual analog scales (VASs) at 4, 24, 48, and 72 h. The time to resume eating and adverse reactions were also recorded. Results: At 24 and 48 h postoperatively, the mean VAS score was significantly higher in the ketorolac group compared to the parecoxib group (5.0 ± 2.3 vs. 3.6 ± 2.2, p = 0.005 and 3.9 ± 2.2 vs. 2.5 ± 1.7, p < 0.001, respectively). However, no significant difference in the mean VAS scores was observed between the two groups at 72 h postoperatively. With regards to postoperative swallowing pain, the ketorolac group exhibited significantly higher mean VAS scores than the parecoxib group at 4, 24, 48, and 72 h postoperatively. Conclusions: Intravenous parecoxib may offer superior analgesic benefits in the early postoperative period, particularly in alleviating swallowing pain, compared to ketorolac in UPPP procedures.

A review of complex hormone regulation in thyroid cancer: novel insights beyond the hypothalamus-pituitary-thyroid axis.

Like the ovaries and prostate, the thyroid exhibits characteristic hormone secretion and regulation. Thyroid cancer (TC), especially differentiated thyroid carcinoma, has typical sex-specific and age-specific hormone-driven clinical features. Previous research has primarily focused on the effects of thyroid stimulating hormone, thyroid hormones, and estrogens on the onset and progression of TC, while the roles of growth hormone (GH), androgens, and glucocorticoids have largely been overlooked. Similarly, few studies have investigated the interactions between hormones and hormone systems. In fact, numerous studies of patients with acromegaly have shown that serum levels of GH and insulin-like growth factor-1 (IGF-1) may be associated with the onset and progression of TC, although the influences of age, sex, and other risk factors, such as obesity and stress, remain unclear. Sex hormones, the GH/IGF axis, and glucocorticoids are likely involved in the onset and progression of TC by regulating the tumor microenvironment and metabolism. The aim of this review was to clarify the roles of hormones and hormone systems in TC, especially papillary thyroid carcinoma, as references for further investigations.

Incidence and Clinical Characteristics of COVID-19 Ophthalmopathy Following the Termination of Dynamic Zero COVID-19 Strategy in China.

Ocular involvement is not uncommon in patients with COVID-19. However, the incidence of COVID-19 ophthalmopathy in COVID-19 patients is still not clear. In this prospective case series study, we recruited 2445 consecutive cases presenting at Neuro-ophthalmology clinic of our Eye Center during the last resurgence of SARS-CoV-2 infection from 8 December 2022 to 15 March 2023 in China, 149 cases were diagnosed as COVID-19 ophthalmopathy, 87 cases were female, with a mean age of 43.2 years, and the mean follow-up time was 15.4 weeks. One hundred and twenty of 149 cases suffered from systemic symptoms mostly manifesting as fever, cough and muscle pain prior to or soon after ocular involvement. The most common COVID-19 ophthalmopathy was optic neuritis (51/149), followed by acute zonal occult outer retinopathy complex disease (31/149), uveitis (17/149), ocular mobility disorder-related (third, fourth, or sixth) cranial nerve neuritis (15/149), anterior ischaemic optic neuropathy (9/149), retinal artery occlusion (8/149), retinal microangiopathy including retinal haemorrhage and cotton wool spot (8/149), viral conjunctivitis (7/149), retinal vein occlusion (3/149), viral keratitis (2/149), ptosis (2/149), and other rare ocular diseases. Except 5 cases with central retinal artery occlusion, other 144 COVID-19 ophthalmopathy cases showed good response to steroid therapy. Our study revealed an incidence of 6.09% for COVID-19 ophthalmopathy in outpatients at our Neuro-ophthalmology clinic during last resurgence of COVID-19 in China, and demonstrated that SARS-CoV-2 infection could induce an initial onset or a relapse of ophthalmic diseases, and that ocular involvement might manifest as the initial or even the only presentation of COVID-19.

A global transcriptional activator involved in the iron homeostasis in cyanobacteria.

Cyanobacteria use a series of adaptation strategies and a complicated regulatory network to maintain intracellular iron (Fe) homeostasis. Here, a global activator named IutR has been identified through three-dimensional chromosome organization and transcriptome analysis in a model cyanobacterium Synechocystis sp. PCC 6803. Inactivation of all three homologous IutR-encoding genes resulted in an impaired tolerance of Synechocystis to Fe deficiency and loss of the responses of Fe uptake-related genes to Fe-deplete conditions. Protein-promoter interaction assays confirmed the direct binding of IutR with the promoters of genes related to Fe uptake, and chromatin immunoprecipitation sequencing analysis further revealed that in addition to Fe uptake, IutR could regulate many other physiological processes involved in intracellular Fe homeostasis. These results proved that IutR is an important transcriptional activator, which is essential for cyanobacteria to induce Fe-deficiency response genes. This study provides in-depth insights into the complicated Fe-deficient signaling network and the molecular mechanism of cyanobacteria adaptation to Fe-deficient environments.

Water-filtered infrared A radiation hyperthermia combined with immunotherapy for advanced gastrointestinal tumours.

This study pioneered the use of WIRA whole-body infrared hyperthermia combined with ICI therapy to treat GIT and verified the feasibility and safety of HIT. The final results showed a DCR of 55.6%, with a median PFS of 53.5 days, median OS of 134 days, and an irAE incidence of 22.2%. Therefore, we believe that HIT can exert multiple synergistic sensitisation effects, thereby providing clinical benefits to patients with advanced GITs, increasing overall safety, and improving patients' QOL.

INTRODUCTION: This study aimed to validate the effectiveness, safety and feasibility of water­filtered infrared A radiation (WIRA) whole­body hyperthermia combined with immune checkpoint inhibitor (ICI) therapy (HIT) and evaluate the real­world clinical application prospects. METHODS: This open­label single­arm phase 2 clinical trial (NCT06022692) aimed to enrol advanced gastrointestinal tumour (GIT) patients with the MSS/pMMR phenotype. The patients were treated with whole­body hyperthermia on Days 1 and 8 of each HIT cycle along with administration of tislelizumab on Day 2. RESULTS: Between 1 June 2020 and 31 May 2022, 18 patients were enrolled in the study, including those with gastric cancer (n = 6), colon cancer (n = 7), rectal cancer (n = 3) and appendiceal cancer (n = 2). As of 19 May 2023, 17 of the 18 patients had died, including 14 deaths caused by tumour progression and three deaths caused by diseases other than cancer, while one patient was still undergoing follow­up. In terms of efficacy, the median DCR was 55.6%, while the median PFS and OS were 53.5 days and 134 days, respectively. Four patients (22.2%) experienced immune­related adverse events, and none of the patients reported grade 3 or higher irAEs. Hyperthermia was followed by an increase in the number of tumour immune­activated cells. CONCLUSIONS: HIT can provide survival benefits in patients with GITs by activating antitumour immune function and shows good safety and feasibility.

Activin A as a potential biomarker for preserved ratio impaired spirometry (PRISm) and clinical outcomes in community-dwelling adults.

INTRODUCTION: This study endeavors to decipher the association between Activin A and PRISm, thereby addressing the potential of Activin A as a serum biomarker for early detection and long-term clinical outcome prediction of PRISm and subsequent all-cause mortality. METHODS: The study sample comprised middle-aged and older adults from the I-Lan Longitudinal Aging Study. Pulmonary function including forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured. Demographic data and laboratory data (including serum Activin A levels) were also collected. Multivariate logistic regression and Cox proportional hazards models were used to identify independent predictors of PRISm and all-cause mortality, respectively. RESULTS: Among 711 eligible participants, 34 % had PRISm. The risk of PRISm elevated with Activin A levels in group quartiles (adjusted odds ratio (aOR), Q2: 1.606 [95 % CI 0.972-2.652], p = 0.064, Q3: 2.666 [1.635-4.348], p < 0.001, Q4: 3.225 [1.965-5.293], p < 0.001). On the other hand, lower hemoglobin (aOR: 1.122, p = 0.041) and higher blood urea nitrogen (BUN) levels (aOR: 1.033, p = 0.048) were associated with increased risk of PRISm. In addition, the PRISm group had a higher all-cause mortality rate (non-PRISm 4.5% vs. PRISm 8.3 %, p = 0.038). Multivariate Cox models also identify a higher level of Activin A as a risk factor of all-cause mortality (aHR: 1.001 [1.000-1.003], p = 0.042). CONCLUSIONS: Higher Activin A quartiles were linked to increased risk of PRISm, along with lower hemoglobin and higher BUN levels. Additonally, elevated Activin A was a significant risk factor of all-cause mortality.

Metagenomic Next-Generation Sequencing for the Diagnosis of Viral Infectious Uveitis and Its Mimics.

PURPOSE: To investigate the value of metagenomic next-generation sequencing (mNGS) for virus detection in patients with suspected viral infectious uveitis. METHODS: In this retrospective, multicenter case series study, 70 patients with suspected viral infectious uveitis were recruited. All patients underwent mNGS test using intraocular fluid samples and serological screening tests for pathogens. Twelve cases also underwent a PCR panel test for herpetic viruses using intraocular fluid samples; 7 cases also underwent aqueous anti-herpetic viral IgG level tests. RESULTS: Among 70 patients with suspected viral infectious uveitis, 34 cases were female, mean age was 45.3 years with a range from 6 to 78 years; 53 cases (75.7%) were diagnosed as infectious uveitis, 17 cases (24.3%) diagnosed as non-infectious uveitis. Among 53 cases with infectious uveitis, herpetic viruses, Bartonella henselae, Toxoplasma gondii, and Treponema pallidum were detected in 43, 6, 4, and 1 case, respectively. Among 43 cases with viral infectious uveitis, herpetic virus was detected in 39 cases by mNGS, the other 4 cases showed negative results in mNGS test, but positive results in 2 cases in serological screening tests, in 1 case in PCR, and in 1 case in aqueous anti-herpetic viral IgG level test, respectively. The sensitivity, specificity, positive predictive value, negative predictive value of mNGS in detecting viruses were 90.7%, 100%, 100%, and 81.0%, respectively. CONCLUSIONS: mNGS is a sensitive and valuable method to detect viruses in intraocular fluid samples, and an alternative for pathogen detection in cases with suspected viral infectious uveitis but negative test results in PCR.

Follistatin-respiratory connection predicting all-cause mortality among community-dwelling middle-to-old age individuals: Results from the I-Lan Longitudinal Study.

OBJECTIVES: The link between aging and pulmonary function decline is well-established, but the underlying mechanisms have yet to be fully revealed. Serum follistatin, a myokine implicated in muscle degeneration, may play a role in age-related pulmonary changes. This study aims to investigate the relationship between serum follistatin levels and pulmonary function decline in community-dwelling older adults, and evaluate their combined association with all-cause mortality. RESEARCH DESIGN AND METHODS: This longitudinal cohort study utilized data from 751 participants aged ≥50 years in the I-Lan Longitudinal Aging Study between 2018-2019. Serum follistatin levels, spirometry results, demographic and clinical data were retrieved. Participants were stratified based on their follistatin levels. Survival curves and group comparisons based on follistatin levels and decline in peak expiratory flow (PEF) using Kaplan-Meier analysis and log-rank tests. Multivariate Cox proportional hazards models were further used to identify independent predictors of all-cause mortality during the 52-month follow-up. RESULTS: Elevated follistatin levels significantly correlated with worse pulmonary function, particularly decreased PEF (p = 0.030). Kaplan-Meier analysis revealed the combination of elevated follistatin levels and decreased PEF was associated with increased risk of all-cause mortality (Log-rank p = 0.023). Cox proportional hazards models further identified that concurrent presence of higher follistatin levels and decreased PEF predicted higher risk of all-cause mortality (adjusted HR 3.58, 95% CI: 1.22-10.53, p = 0.020). CONCLUSION: Higher serum follistatin levels correlate with decreased pulmonary function, specifically PEF decline, in community-dwelling older adults. Furthermore, the coexistence of elevated follistatin levels and decreased PEF was associated with risk of all-cause mortality. Follistatin may serve as a biomarker for pulmonary aging and related adverse outcomes.

Genistein-Chitosan Derivative Nanoparticles for Targeting and Enhancing the Anti-Breast Cancer Effect of Tamoxifen In Vitro.

Tamoxifen (TAM) is a classical anti-estrogenic drug that antagonizes estrogen by competitively binding to estrogen receptor α (ERα). However, drug resistance to TAM remains a significant challenge in breast cancer treatment. In this study, we aimed to design an actively targeted drug delivery system to enhance the proliferation inhibitory effects of TAM on ER positive breast cancer cells. Herein, chitosan (CS) was modified with genistein (GEN) to obtain the actively targeted GEN-CS. The TAM-loaded nanoparticles (TAM-GEN-CS-NPs) were constructed using an ionic-crosslinking method, with GEN-CS as the carrier material and sodium tripolyphosphate (TPP) as the crosslinking agent. As a result, TAM-GEN-CS-NPs exhibited a spherical morphology with an average size of 299.8 nm. The encapsulation efficiency and drug loading content were 85.77% and 14.13 µg/mg, respectively. Compared with free TAM, TAM-GEN-CS-NPs displayed obvious slow-release performance. In vitro cellular assays demonstrated that TAM-GEN-CS-NPs had active targeting and proliferation inhibitory effects on MCF-7 cells. The IC50 of TAM and TAM-GEN-CS-NPs were 10.25 µg/mL and 7.22 µg/mL, respectively. More importantly, the combination index (CI) value of TAM and GEN was less than 1, indicating synergistic effects. Therefore, TAM-GEN-CS-NPs hold the potential to enhance TAM therapy for breast cancer through active targeting and synergistic treatment strategies.

Self-calibrated atom-interferometer gyroscope by modulating atomic velocities.

Atom-interferometer gyroscopes have attracted much attention for their long-term stability and extremely low drift. For such high-precision instruments, self-calibration to achieve an absolute rotation measurement is critical. In this work, we propose and demonstrate the self-calibration of an atom-interferometer gyroscope. This calibration is realized by using the detuning of the laser frequency to control the atomic velocity, thus modulating the scale factor of the gyroscope. The modulation determines the order and the initial phase of the interference stripe, thus eliminating the ambiguity caused by the periodicity of the interferometric signal. This self-calibration method is validated through a measurement of the Earth's rotation rate, and a relative uncertainty of 162 ppm is achieved. Long-term stable and self-calibrated atom-interferometer gyroscopes have important applications in the fields of fundamental physics, geophysics, and long-time navigation.

Microwave hyperthermia enhances radiosensitization by decreasing DNA repair efficiency and inducing oxidative stress in PC3 prostatic adenocarcinoma cells.

PURPOSE: Radiotherapy (RT) is the primary treatment for prostate cancer (PCa); however, the emergence of castration-resistant prostate cancer (CRPC) often leads to treatment failure and cancer-related deaths. In this study, we aimed to explore the use of microwave hyperthermia (MW-HT) to sensitize PCa to RT and investigate the underlying molecular mechanisms. METHODS: We developed a dedicated MW-HT heating setup, created an in vitro and in vivo MW-HT + RT treatment model for CRPC. We evaluated PC3 cell proliferation using CCK-8, colony experiments, DAPI staining, comet assay and ROS detection method. We also monitored nude mouse models of PCa during treatment, measured tumor weight, and calculated the tumor inhibition rate. Western blotting was used to detect DNA damage repair protein expression in PC3 cells and transplanted tumors. RESULTS: Compared to control, PC3 cell survival and clone formation rates decreased in RT + MW-HT group, demonstrating significant increase in apoptosis, ROS levels, and DNA damage. Lower tumor volumes and weights were observed in treatment groups. Ki-67 expression level was reduced in all treatment groups, with significant decrease in RT + MW-HT groups. The most significant apoptosis induction was confirmed in RT + MW-HT group by TUNEL staining. Protein expression levels of DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways significantly decreased in RT + MW-HT groups. CONCLUSION: MW-HT + RT treatment significantly inhibited DNA damage repair by downregulating DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways, leading to increased ROS levels, aggravate DNA damage, apoptosis, and necrosis in PC3 cells, a well-established model of CRPC.

Influence of vaccination on critical COVID-19 patients with acute respiratory failure: a retrospective cohort study.

BACKGROUND: Despite vaccines' effectiveness in reducing COVID-19 infection rates and disease severity, their impact on critical patients presenting with acute respiratory failure is elusive. The aim of this study was to further investigate the influence of vaccination on mortality rates among severely ill COVID-19 patients experiencing acute respiratory failure. METHODS: This retrospective cohort study was carried out at a tertiary medical center in Taiwan. From April to September 2022, patients who tested positive for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through reverse transcription polymerase chain reaction (RT-PCR) and subsequently experienced acute respiratory failure were included in the study. Baseline characteristics, including vaccination history, along with information regarding critical illness and clinical outcomes, were gathered and compared between patients who received the vaccine and those who did not. RESULTS: A total of 215 patients with COVID-19 exhibiting acute respiratory failure, as confirmed via RT‒PCR, were included in the analysis. Of this cohort, sixty-six (30.7%) patients died within 28 days. Neither administration of the vaccine nor achievement of primary series vaccination status had a significantly different effect on 28 day mortality, number of viral shedding events, acute respiratory distress syndrome (ARDS) incidence or other clinical outcomes. Patients who received the booster vaccine and completed the primary series showed a tendency of increased 28 days of ventilator-free status, though this difference was not statistically significant (p = 0.815). CONCLUSIONS: Vaccination status did not significantly influence mortality rates, the occurrence of ARDS, or the viral shedding duration in COVID-19 patients with acute respiratory failure.

Index admission cholecystectomy for biliary acute pancreatitis or choledocholithiasis reduces 30-day readmission rates in children.

BACKGROUND: Adult patients with biliary acute pancreatitis (BAP) or choledocholithiasis who do not undergo cholecystectomy on index admission have worse outcomes. Given the paucity of data on the impact of cholecystectomy during index hospitalization in children, we examined readmission rates among pediatric patients with BAP or choledocholithiasis who underwent index cholecystectomy versus those who did not. METHODS: Retrospective study of children (< 18 years old) admitted with BAP, without infection or necrosis (ICD-10 K85.10), or choledocholithiasis (K80.3x-K80.7x) using the 2018 National Readmission Database (NRD). Exclusion criteria were necrotizing pancreatitis with or without infected necrosis and death during index admission. Multivariable logistic regression was performed to identify factors associated with 30-day readmission. RESULTS: In 2018, 1122 children were admitted for index BAP (n = 377, 33.6%) or choledocholithiasis (n = 745, 66.4%). Mean age at admission was 13 (SD 4.2) years; most patients were female (n = 792, 70.6%). Index cholecystectomy was performed in 663 (59.1%) of cases. Thirty-day readmission rate was 10.9% in patients who underwent cholecystectomy during that index admission and 48.8% in those who did not (p < 0.001). In multivariable analysis, patients who underwent index cholecystectomy had lower odds of 30-day readmission than those who did not (OR 0.16, 95% CI 0.11-0.24, p < 0.001). CONCLUSIONS: Index cholecystectomy was performed in only 59% of pediatric patients admitted with BAP or choledocholithiasis but was associated with 84% decreased odds of readmission within 30 days. Current guidelines should be updated to reflect these findings, and future studies should evaluate barriers to index cholecystectomy.

The Regulation Role of the Gut-Islets Axis in Diabetes.

The gut-islets axis is an important endocrine signaling axis that regulates the function of islets by modulating the gut micro-environment and its endocrine metabolism. The discovery of intestinal hormones, such as GLP-1 and GIP, has established a preliminary link between the gut and the islet, paving the way for the development of GLP-1 receptor agonists based on the regulation theory of the gut-islets axis for diabetes treatment. This discovery has created a new paradigm for diabetes management and rapidly made the regulation theory of the gut-islets axis a focal point of research attention. Recent years, with in-depth study on gut microbiota and the discovery of intestinal-derived extracellular vesicles, the concept of gut endocrine and the regulation theory of the gut-islets axis have been further expanded and updated, offering tremendous research opportunities. The gut-islets axis refers to the complex interplay between the gut and the islet, which plays a crucial role in regulating glucose homeostasis and maintaining metabolic health. The axis involves various components, including gut microbiota, intestinal hormones, amino acids and ACE2, which contribute to the communication and coordination between the gut and the islet.