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.

Engineering the thermal stability of a polyphosphate kinase by ancestral sequence reconstruction to expand the temperature boundary for an industrially applicable ATP regeneration system.

ATP-dependent energy-consuming enzymatic reactions are widely used in cell-free biocatalysis. However, the direct addition of large amounts of expensive ATP can greatly increase cost, and enzymatic production is often difficult to achieve as a result. Although a polyphosphate kinase (PPK)-polyphosphate-based ATP regeneration system has the potential to solve this challenge, the generally poor thermal stability of PPKs limits the widespread use of this method. In this paper, we evaluated the thermal stability of a PPK from Sulfurovum lithotrophicum (SlPPK2). After directed evolution and computation-supported design, we found that SlPPK2 is very recalcitrant and cannot acquire beneficial mutations. Inspired by the usually outstanding stability of ancestral enzymes, we reconstructed the ancestral sequence of the PPK family and used it as a guide to construct three heat-stable variants of SlPPK2, of which the L35F/T144S variant has a half-life of more than 14 h at 60°C. Molecular dynamics simulations were performed on all enzymes to analyze the reasons for the increased thermal stability. The results showed that mutations at these two positions act synergistically from the interior and surface of the protein, leading to a more compact structure. Finally, the robustness of the L35F/T144S variant was verified in the synthesis of nucleotides at high temperature. In practice, the use of this high-temperature ATP regeneration system can effectively avoid byproduct accumulation. Our work extends the temperature boundary of ATP regeneration and has great potential for industrial applications.IMPORTANCEATP regeneration is an important basic applied study in the field of cell-free biocatalysis. Polyphosphate kinase (PPK) is an enzyme tool widely used for energy regeneration during enzymatic reactions. However, the thermal stability of the PPKs reported to date that can efficiently regenerate ATP is usually poor, which greatly limits their application. In this study, the thermal stability of a difficult-to-engineer PPK from Sulfurovum lithotrophicum was improved, guided by an ancestral sequence reconstruction strategy. The optimal variant has a 4.5-fold longer half-life at 60°C than the wild-type enzyme, thus enabling the extension of the temperature boundary for ATP regeneration. The ability of this variant to regenerate ATP was well demonstrated during high-temperature enzymatic production of nucleotides.

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.

Index admission cholecystectomy for acute cholecystitis reduces 30-day readmission rates in pediatric patients.

BACKGROUND: Adult patients with cholecystitis who do not undergo cholecystectomy on index admission have worse outcomes, however, there is a paucity of data of the role of cholecystectomy during index hospitalization in the pediatric population. Our aim was to determine outcomes and readmission rates among pediatric patients with cholecystitis who underwent index cholecystectomy versus those who did not. METHODS: We performed a retrospective study of pediatric (< 18 years old) admitted with acute cholecystitis (AC) requiring hospitalization using the 2018 National Readmission Database (NRD). Exclusion criteria included age ≥ 18 years and death on index admission. Multivariable logistic regression was performed to identify factors associated with 30-day readmissions. RESULTS: We identified 550 unique index acute cholecystitis admissions. Mean age was 14.6 ± 3.0 years. Majority of patients were female (n = 372, 67.6%). Index cholecystectomy was performed in (n = 435, 79.1%) of cases. Thirty-day readmission rate was 2.8% in patients who underwent index cholecystectomy and 22.6% in those who did not (p < 0.001). On multivariable analysis, patients who did not undergo index cholecystectomy had higher odds of 30-day readmission than those who did not (OR 10.66, 95% CI 5.06-22.45, p < 0.001). Female patients also had higher odds of 30-day readmission compared to males (OR 3.37, 95% CI 1.31-8.69). CONCLUSIONS: Patients who did not undergo index cholecystectomy had over tenfold increase in odds of 30-day readmission. Further research is required to understand the barriers to index cholecystectomy despite society recommendations and clear clinical benefit.

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.

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.

Prognostic Factors in Philadelphia Chromosome-Positive Acute Myeloid Leukemia Using Fluorescence in Situ Hybridization.

BACKGROUND: Philadelphia chromosome-positive acute myeloid leukemia (Ph+ AML) is a rare leukemia subtype first classified by the World Health Organization in 2016. The incidence of Ph+ AML is approximately 0.5 - 3%, and its prognosis is poor. Ph+ AML with additional chromosomal abnormalities in children has rarely been reported, and its treatment and prognosis remain uncertain. METHODS: We retrospectively analyzed 649 patients with AML from 2006 - 2021. Six (0.9%) patients with Ph+ AML were identified and treated with conventional chemotherapy. The clinical features and prognoses were retrospectively analyzed. RESULTS: Six cases of AML with a Ph chromosome were reported. One of the six individuals exhibited a biphenotypic immunophenotype, one exhibited a simple myeloid immunophenotype, and the other four exhibited myeloid and lymphoid expression. Karyotypic analysis (R banding) was performed in six cases, four of which were classical Ph chromosomal abnormalities, two of which had additional abnormalities outside the Ph chromosome. Fluorescence in situ hybridization (FISH) analysis using the BCR/ABL fusion gene distinguished that the BCR major breakpoint break in three cases was type P210 and the BCR minor breakpoint break in three cases was type P190. The complete remission rate of the six patients in this study using conventional chemotherapy was 60%, with a median survival time of 7.5 months. CONCLUSIONS: In summary, Ph+ AML is a heterogeneous disease often associated with additional chromosomal abnormalities. Ph+ AML is seen with a lymphoid immunophenotype and alterations in associated genes such as the IGH gene. Adults were predominantly P210 and two cases in children were both P190. Conventional treatments are less effective, and there are no standard treatment regimens.

Clinical characteristics and outcomes among critically ill patients with cancer and COVID-19-related acute respiratory failure.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has affected individuals worldwide, and patients with cancer are particularly vulnerable to COVID-19-related severe illness, respiratory failure, and mortality. The relationship between COVID-19 and cancer remains a critical concern, and a comprehensive investigation of the factors affecting survival among patients with cancer who develop COVID-19-related respiratory failure is warranted. We aim to compare the characteristics and outcomes of COVID-19-related acute respiratory failure in patients with and without underlying cancer, while analyzing factors affecting in-hospital survival among cancer patients. METHODS: We conducted a retrospective observational study at Taipei Veterans General Hospital in Taiwan from May to September 2022, a period during which the omicron variant of the severe acute respiratory syndrome coronavirus 2 was circulating. Eligible patients had COVID-19 and acute respiratory failure. Clinical data, demographic information, disease severity markers, treatment details, and outcomes were collected and analyzed. RESULTS: Of the 215 enrolled critically ill patients with COVID-19, 65 had cancer. The patients with cancer were younger and had lower absolute lymphocyte counts, higher ferritin and lactate dehydrogenase (LDH) concentrations, and increased vasopressor use compared with those without cancer. The patients with cancer also received more COVID-19 specific treatments but had higher in-hospital mortality rate (61.5% vs 36%, P = 0.002) and longer viral shedding (13 vs 10 days, P = 0.007) than those without cancer did. Smoking [odds ratio (OR): 5.804, 95% confidence interval (CI): 1.847-39.746], elevated LDH (OR: 1.004, 95% CI: 1.001-1.012), vasopressor use (OR: 5.437, 95% CI: 1.202-24.593), and new renal replacement therapy (OR: 3.523, 95% CI: 1.203-61.108) were independent predictors of in-hospital mortality among patients with cancer and respiratory failure. CONCLUSION: Critically ill patients with cancer experiencing COVID-19-related acute respiratory failure present unique clinical features and worse clinical outcomes compared with those without cancer. Smoking, elevated LDH, vasopressor use, and new renal replacement therapy were risk factors for in-hospital mortality in these patients.

Impact of Telemedicine on No-Show Rates in an Ambulatory Gastroenterology Practice.

Background: Studies suggest that telemedicine worsens health care disparities in certain groups, partly owing to a lack of access to appropriate technology or poor technological literacy. Our aim was to use clinic no-show data to determine the impact of telemedicine on patient access to care in the ambulatory gastroenterology setting. Methods: Single-center retrospective study of ambulatory in-person and telemedicine clinic appointments comparing the 15-month prepandemic (PP) with the first 15 months during the pandemic (DTP) using an administrative database. Statistical analysis was performed using univariate and multivariable logistic regression. Results: About 9,746 and 12,808 patient-encounters were scheduled PP and DTP respectively. The no-show rate decreased from 9.8% to 6.9% DTP (p < 0.001). The no-show rate decreased for Black (p = 0.02) and non-Hispanic White patients (p = 0.018). The no-show rate increased for LatinX (p < 0.001) and Asian (p = 0.007) patients. In multivariate analysis, older patients and patients identifying as Black, Asian, or LatinX all had higher odds of no-show DTP (p < 0.05 for all). Patients from high-income counties were 43% less likely to no-show than those in the lowest income counties. Conclusions: The transition to telemedicine improves health care access by decreasing the overall no-show rate. Some groups have been negatively affected, including the older, lower income, LatinX, and Asian populations. Future studies should aim to identify the risk factors within these populations that can be modified to increase health care participation, including targeted application of in-person visits, and improved technology to drive engagement.

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.

Telecytology versus in-room cytopathologist for EUS-guided FNA or fine-needle biopsy sampling of solid pancreatic lesions.

BACKGROUND AND AIMS: Rapid on-site-evaluation (ROSE) with an in-room cytopathologist (ROSE-P) has been shown to improve the diagnostic yield of specimens obtained from patients undergoing EUS-guided FNA or fine-needle biopsy sampling (EUS-FNAB) of pancreatic lesions. Recently, there has been an increased interest and use of ROSE using telecytology (ROSE-T) to optimize clinical workflows and to address social distancing mandates created during the coronavirus disease 2019 pandemic. The purpose of this study was to compare diagnostic outcomes of ROSE-P and ROSE-T. METHODS: A single-center cohort study of patients who underwent EUS-FNAB of solid pancreatic lesions with ROSE was conducted. The primary outcome was overall diagnostic yield of cancer. All patients who underwent EUS-FNAB were entered into a prospectively maintained database. Statistical analyses were performed using descriptive statistics and univariate analysis. RESULTS: There were 165 patients in each arm. There was no difference in diagnostic yield between ROSE-P and ROSE-T (96.4% vs 94.5%, P = .428). ROSE-T was associated with an increased use of 22-gauge needles (P = .006) and more needle passes (P < .001). No significant differences were found in age, gender, lesion size, needle type, procedure times, or adverse events between the 2 groups (P < .05 for all). More pancreatic tail lesions were sampled in the ROSE-P group (P < .001). CONCLUSIONS: ROSE-T was not associated with any difference in final histologic diagnosis for EUS-FNAB of solid pancreatic masses. This has important implications for optimizing clinical workflows.

Retinal microvascular changes in diabetic patients with diabetic nephropathy.

BACKGROUND: To explore the characteristics of retina microvascular changes in patients with diabetic nephropathy (DN) and its risk factors. METHODS: Retrospective, observational study. 145 patients with type 2 diabetic mellitus (DM) and DN were included in the study. Demographic and clinical parameters were obtained from medical records. Presence of diabetic retinopathy (DR), hard exudates (HEs) and diabetic macular edema (DME) were evaluated according to the color fundus images, optical coherence tomography (OCT) and fluorescence angiography (FFA). RESULTS: DR accounted for 61.4% in type 2 DM patients with DN, of which proliferative diabetic retinopathy (PDR) accounted for 23.6% and sight threatening DR accounted for 35.7%. DR group had significantly higher levels of low-density lipoprotein cholesterol (LDL-C) (p = 0.004), HbA1c (P = 0.037), Urine albumin creatine ratio (ACR) (p < 0.001) and lower level of estimated glomerular filtration rate (eGFR) (P = 0.013). Logistic regression analysis showed DR was significantly associated with ACR stage (p = 0.011). Subjects with ACR stage3 had higher incidence of DR compared with subjects with ACR stage1 (OR = 24.15, 95%CI: 2.06-282.95). 138 eyes of 138 patients were analyzed for HEs and DME, of which 23.2% had HEs in posterior pole and 9.4% had DME. Visual acuity was worse in HEs group than in non-HEs group. There was significant difference in the LDL-C cholesterol level, total cholesterol (CHOL) level and ACR between HEs group and non-HEs group. CONCLUSIONS: A relatively higher prevalence of DR was found in type 2 DM patients with DN. ACR stage could be recognized as a risk factor for DR in DN patients. Patients with DN needs ophthalmic examination more timely and more frequently.

Over-the-Scope Clips Versus Standard Endoscopic Treatment for First Line Therapy of Non-variceal Upper Gastrointestinal Bleeding: Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Over-The-Scope Clips (OTSC) use have shown promising results for first line treatment of non-variceal upper gastrointestinal bleeding (NVUGIB). We conducted this meta-analysis to compare outcomes in patients treated with OTSC versus standard endoscopic intervention for first line endoscopic treatment of NVUGIB. METHODS: We reviewed several databases from inception to December 9, 2022 to identify studies comparing OTSC and standard treatments as the first line treatment for NVUGIB. The outcomes assessed included re-bleeding, initial hemostasis, need for vascular embolization, mortality, need for repeat endoscopy, 30 day readmission rate, and need for surgery. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using random effect model. Heterogeneity was assessed by I2 statistic. RESULTS: We included 11 studies with 1608 patients (494 patients in OTSC group and 1114 patients in control group). OTSC use was associated with significantly lower risk of re-bleeding (RR, 0.58; 95% CI 0.41-0.82). We found no significant difference in rates of initial hemostasis (RR, 1.05; 95% CI 0.99- 1.11), vascular embolization rates (RR, 0.93; 95% CI 0.40- 2.13), need for repeat endoscopy (RR, 0.78; 95% CI 0.40-1.49), 30 day readmission rate (RR, 0.59; 95% CI 0.17-2.01), need for surgery (RR, 0.81; 95% CI 0.29-2.28) and morality (RR, 0.69; 95% CI 0.38-1.23). CONCLUSIONS: OTSC are associated with significantly lower risk of re-bleeding compared to standard endoscopic treatments when used as first line endoscopic therapy for NVUGIB.

Three Novel Variants of t(8;21) and Classical t(8;21) Translocation in Acute Myeloid Leukemia.

BACKGROUND: Some studies have discussed adverse prognosis factors of AML with t(8;21) to be closely related to genetic changes. METHOD: We reviewed 58 cases of AML in children and adults with t(8;21)(q22;q22) translocation. RESULTS: Five variant translocation cases were observed: t(8;17;21)(q22;q12;q22) (case 1), t(1;8;21)(q12;q22;q22) (case 2), and t(8;12;21)(q22;p13;q22) (case 3). The translocations were first observed in three children. Case 2 was cured with chemotherapy, and the cut-off date of observation was 120 months. Case 3 relapsed after 1 year (overall survival [OS], 14 months). Patients with AML with t(8;21) variant translocation have different prognoses and require further study. Forty-two of the 58 cases were included in the survival analysis. Cox regression analysis showed that progression-free survival (PFS) was correlated with age group, white blood cell (WBC) count, bone marrow blast ratio, and loss of Y chromosome (-Y). Overall survival (OS) was correlated with age group, WBC count, and -Y. Childhood leukemia with t(8;21) has a better prognosis than adult leukemia. Survival curves were drawn according to age and cytogenetic abnormalities. CONCLUSIONS: Progression-free survival was correlated with age, white blood cell (WBC) count, bone marrow blast ratio, and loss of Y chromosome (-Y). OS was correlated with age group, WBC count, and -Y chromosome. Child-hood leukemia with t(8;21) has a better prognosis than adult leukemia.

Inhibition of mitochondrial calcium uptake by Ru360 enhances the effect of 1800 MHz radio-frequency electromagnetic fields on DNA damage.

Today, the existence of radio-frequency electromagnetic fields (RF-EMF) emitted from cell phones, wireless routers, base stations, and other sources are everywhere around our living environment, and the dose is increasing. RF-EMF have been reported to be cytotoxic and supposed to be a risk factor for various human diseases, thus, more attention is necessary. In recent years, interfere with mitochondrial calcium uptake by using mitochondrial calcium uniporter (MCU) inhibitor were suggested to be potential clinical treatment in mitochondrial calcium overload diseases, like neurodegeneration, ischemia/reperfusion injury, and cancer, but whether this approach increases the health risk of RF-EMF exposure are unknown. To address our concern, we did a preliminary study to determine whether inhibition of MCU will increase the genotoxicity of RF-EMF exposure in cells, and found that short-time (15 min) exposure to 1800 MHz RF-EMF induced significant DNA damage and cell apoptosis in mouse embryonic fibroblasts (MEFs) treated with Ruthenium 360 (Ru360), a specific inhibitor of MCU, but no significant effects on cell cycle, cell proliferation, or cell viability were observed. In conclusion, our results indicated that inhibiting MCU increases the genotoxicity of RF-EMF exposure, and more attention needs to be paid to the possible health impact of RF-EMF exposure under these treatments.

Surfactant Additives Containing Hydrophobic Fluorocarbon Chains and Hydrophilic Sulfonate Anion for Highly Reversible Zn Anode.

Aqueous zinc-ion batteries (AZIBs) show enormous potential as a large-scale energy storage technique. However, the growth of Zn dendrites and serious side reactions occurring at the Zn anode hinder the practical application of AZIBs. For the first time, we reported a fluorine-containing surfactant, i.e., potassium perfluoro-1-butanesulfonate (PPFBS), as an additive to the 2 M ZnSO4 electrolyte. Benefitting from its hydrophilic sulfonate anion and hydrophobic long fluorocarbon chain, PPFBS can promote the uniform distribution of Zn2+ flux at the anode/electrolyte interface, allowing the Zn/Zn cell to cycle for 2200 h. Furthermore, PPFBS could inhibit side reactions due to the existence of the perfluorobutyl sulfonate (C4F9SO3-) adsorption layer and the presence of C4F9SO3- in the solvation structure of Zn2+. The former can reduce the amount of H2O molecules and SO42- in contact with the Zn anode and C4F9SO3- entering the Zn2+-solvation structure by replacing SO42-. The Zn/Cu cell exhibits a superior average CE of 99.47% over 500 cycles. When coupled with the V2O5 cathode, the full cell shows impressive cycle stability. This work provides a simple, effective, and economical solution to the common issues of the Zn anode.

Suppressive effects of pterostilbene on human cytomegalovirus (HCMV) infection and HCMV-induced cellular senescence.

BACKGROUND: Human cytomegalovirus (HCMV), a member of the ß-herpesvirus family, causes the establishment of a latent infection that persists throughout the life of the host and can be reactivated when immunity is weakened. To date, there is no vaccine to prevent HCMV infection, and clinically approved drugs target the stage of viral replication and have obvious adverse reactions. Thus, development of novel therapeutics is urgently needed. METHODS: In the current study, we identified a naturally occurring pterostilbene that inhibits HCMV Towne strain replication in human diploid fibroblast WI-38 cells through Western blotting, qPCR, indirect immunofluorescence assay, tissue culture infective dose assays. The time-of-addition experiment was carried out to identify the stage at which pterostilbene acted. Finally, the changes of cellular senescence biomarkers and reactive oxygen species production brought by pterostilbene supplementation were used to partly elucidate the mechanism of anti-HCMV activity. RESULTS: Our findings revealed that pterostilbene prevented lytic cytopathic changes, inhibited the expression of viral proteins, suppressed the replication of HCMV DNA, and significantly reduced the viral titre in WI-38 cells. Furthermore, our data showed that pterostilbene predominantly acted after virus cell entry and membrane fusion. The half-maximal inhibitory concentration was determined to be 1.315 µM and the selectivity index of pterostilbene was calculated as 26.73. Moreover, cell senescence induced by HCMV infection was suppressed by pterostilbene supplementation, as shown by a decline in senescence-associated ß-galactosidase activity, decreased production of reactive oxygen species and reduced expression of p16, p21 and p53, which are considered biomarkers of cellular senescence. CONCLUSION: Together, our findings identify pterostilbene as a novel anti-HCMV agent that may prove useful in the treatment of HCMV replication.

A case report of acute testicular pain secondary to segmental testicular infarction.

BACKGROUND: Segmental testicular infarction is a rare condition that often occurs in the upper pole of the left testicle and usually presents with acute onset of scrotal pain. Contrast-enhanced ultrasound and MR are essential for diagnosing and differentiating segmental testicular infarction in clinical practice, and conservative treatment can only be adopted after a definitive diagnosis. In the present case, after conservative treatment, the infarct volume was reduced, the blood flow around the infarct was increased, and blood flow signals appeared in the infarct. We performed a correlation analysis to investigate the causes of these changes. CASE PRESENTATION: A 33-year-old male, without any specific disease history, was admitted to the hospital with a 5-day history of left testicular pain, and the imaging showed focal necrosis of the left testicle with hemorrhage. He was diagnosed with segmental testicular infarction after differentiating and excluding it from malignant tumors. Conservative medical treatment was given, and the symptoms of testicular pain were relieved after treatment. After discharge, regular reexamination at follow-ups showed that the infarct's size was reduced, the blood flow around the infarct was increased, and blood flow signals appeared in the infarct. CONCLUSION: Conservative treatment has become the standard treatment currently adopted after confirming the diagnosis of segmental testicular infarction through contrast-enhanced ultrasound and MR. The blood flow changes in and around the focus of testicular infarction can be related to various factors. At present, relevant conclusions of the underlying mechanisms were mainly deduced from infarction studies of other related organs such as the heart and brain; thus, the specific pathological mechanism needs further experimental verification.

Exposure to 10 Hz Pulsed Magnetic Field Induced Slight Apoptosis and Reactive Oxygen Species in Primary Human Gingival Fibroblasts.

Extremely low frequency pulsed magnetic fields (MFs) have been increasingly used as an effective method in oral therapy, but its potential impact on health has not been clarified. In this study, we investigated the impact of 10 Hz pulsed MF exposure on primary human gingival fibroblasts (HGFs) derived from eight healthy persons (four males and four females). Cells were exposed to 10 Hz pulsed MFs at 1.0 mT for 24 h. Cell apoptosis, cell cycle progression, intracellular reactive oxygen species levels, DNA damage, and cell proliferation were determined after exposure. The results showed that 10 Hz pulsed MFs exposure have slight effects on cellular apoptosis, cell cycle progression, and DNA damage in primary HGFs from some but not all samples. In addition, no significant effect was found on cell proliferation. © 2022 Bioelectromagnetics Society.

The characteristics and treatment strategy for transolecranon fracture-dislocation of the elbow in children: a retrospective study.

BACKGROUND: Transolecranon fracture-dislocation of the elbow is rarely seen in children. The purpose of this retrospective study was to discuss the pathological characteristics and treatment strategy for this injury in children. METHODS: From October 2016 to March 2019, 15 patients seen and treated at our institutions for transolecranon fracture-dislocation of the elbow were identified, and their medical records and radiographs were reviewed retrospectively. There were 11 boys and 4 girls, with an average age of 8.3 years (from 5 to 14 years). The left arm was involved in 10 cases, and the right arm was involved in 5 cases. Type I (simple fracture) was found in 11 cases, and type II (comminuted fracture) was found in 4 cases, 3 of which with coronoid process involved. Closed reduction was successful under local anaesthesia in 14 cases but failed in 1 case. In 11 patients with type I fractures, 10 received fixation of Kirschner wire and tension band, and one patient underwent bone plate fixation. In 4 patients with comminuted fractures (type II), internal fixation was performed with Kirschner wires combined with reconstruction plates. RESULTS: The 15 patients were followed up for 24 to 48 months (average, 30.2 months). The final evaluation showed fine anatomical relationship of the elbow in all with no complications observed. Failure of internal fixation did not occur in any patient. The fractures acquired bony union in all patients after 8 to 12 weeks (average, 9.6 weeks). The therapeutic efficacy was evaluated at the final follow-up by the Mayo elbow performance score (MEPS) as excellent in 11 cases, good in 3 cases and fair in one case. CONCLUSIONS: As a type of complicated fracture-dislocation of the elbow, the transolecranon fracture-dislocation is rare in children. The fracture is mainly simple type. Treatment options depend on the type of fracture-dislocation. Only anatomical reduction of the olecranon fracture and restoration of a normal trochlear notch can lead to a stable humeroradial joint and good clinical efficacy.