Risk Factors for Bladder Neck Contracture following Transurethral Resection of the Prostate in Patients with Benign Prostatic Enlargement.

INTRODUCTION: Benign prostatic enlargement (BPE) and lower urinary tract symptoms present challenges in aging men, often addressed through transurethral resection of the prostate (TURP). Despite technological advancements, bladder neck contracture (BNC) remains a concern. This study explores predictors, including comorbidities, influencing BNC after TURP. METHODS: A retrospective cohort study at Changhua Christian Hospital analyzed 2041 BPE patients undergoing bipolar TURP. Preoperative urinary catheterization and resection speed were categorized. Patient data included demographics, comorbidities, operative details, and outcomes. Statistical analyses utilized χ2, Kruskal-Wallis tests, and Cox regression models. RESULTS: Within 3 years, 306 (15%) patients developed BNC. Univariate Cox regression identified chronic heart failure (p = 0.033), chronic obstructive pulmonary disease (COPD; p = 0.002), preoperative urinary catheterization (p < 0.001), and low resection speed (p = 0.045) as significant BNC risk factors. Notably, COPD (p = 0.011) and preoperative urinary catheterization (p < 0.001) emerged as independent risk factors for BNC development in multivariate Cox regression analysis. CONCLUSIONS: Preoperative urinary catheterization and COPD were significant predictors of BNC post-TURP, while resection speed showed no significant influence. These findings offer clinicians insights for risk assessment, enhancing patient outcomes, and optimizing resources post-TURP.

Utilization of Ureteral Access Sheath in Retrograde Intrarenal Surgery: A Systematic Review and Meta-Analysis.

Background and Objectives: This paper evaluates the efficacy and safety of ureteral access sheath (UAS) utilization in retrograde intrarenal surgery (RIRS). Materials and Methods: We searched PubMed, Embase, and the Cochrane Library up to 30 August 2023. The inclusion criteria comprised English-language original studies on RIRS with or without UAS in humans. The primary outcome was SFR, while the secondary outcomes included intraoperative and postoperative complications, the lengths of the operation and the hospitalization period, and the duration of the fluoroscopy. Subgroup analyses and a sensitivity analysis were performed. Publication bias was assessed using funnel plots and Egger's regression tests. Dichotomous variables were analyzed using odds ratios (ORs) with 95% confidence intervals (CIs), while mean differences (MDs) were employed for continuous variables. Results: We included 22 studies in our analysis. These spanned 2001 to 2023, involving 12,993 patients and 13,293 procedures. No significant difference in SFR was observed between the UAS and non-UAS groups (OR = 0.90, 95% CI 0.63-1.30, p = 0.59). Intraoperative (OR = 1.13, 95% CI 0.75-1.69, p = 0.5) and postoperative complications (OR = 1.29, 95% CI 0.89-1.87, p = 0.18) did not significantly differ between the groups. UAS usage increased operation times (MD = 8.30, 95% CI 2.51-14.10, p = 0.005) and fluoroscopy times (MD = 5.73, 95% CI 4.55-6.90, p < 0.001). No publication bias was detected for any outcome. Conclusions: In RIRS, UAS usage did not significantly affect SFR, complications, or hospitalization time. However, it increased operation time and fluoroscopy time. Routine UAS usage is not supported, and decisions should be patient-specific. Further studies with larger sample sizes and standardized assessments are needed to refine UAS utilization in RIRS.

Serum vitamin D levels in females with urinary incontinence: a meta-analysis of observational trials.

INTRODUCTION AND HYPOTHESIS: The association of vitamin D deficiency with female urinary incontinence is unclear. METHODS: A systematic review of English and non-English articles was conducted. All observational studies in databases including PubMed, EMBASE, the Cochrane Library Trials Register, and Google Scholar were searched until 5 October 2020. Additional studies were identified by contacting clinical experts and searching the bibliographies and abstracts of the compiled articles. Search terms included urinary incontinence and vitamin D. Article data, including study quality indicators, were independently extracted by two authors using predefined data fields. RESULTS: Two cohort studies, four case-control studies and five cross-sectional studies were included in the qualitative synthesis. Two cohort studies and one cross-sectional study, with a total of 2501 females, were included in the meta-analysis. Heterogeneity among the three studies was not observed (I2 = 0.0%, P = 0.69). All pooled analyses were based on fixed-effects models. No difference in vitamin D level was observed between the urinary incontinence group and the control group (mean difference 0.07 ng/ml; 95% confidence interval [CI] -0.57-0.72, P = 0.81, I2 = 0%). CONCLUSIONS: Our meta-analysis revealed that adult females with urinary incontinence did not have lower serum vitamin D levels than control females.

Early-onset prostate cancer is associated with increased risks of disease progression and cancer-specific mortality.

OBJECTIVE: Prostate cancer (PCa) incidence has stabilized but not in patients at a young age. We assessed patient characteristics and disease progression in early-onset PCa. METHODS: A retrospective cohort of 28,039 newly diagnosed PCa patients aged ≥35 years was constructed using the Taiwan Cancer Registry in 2008-2016. Patients were categorized by age at diagnosis (≤54, 55-59, 60-69, 70-74, and ≥75 years). The clinical stage at diagnosis, Gleason score, prostate-specific antigen level at diagnosis, Charlson's comorbidity index, and primary and secondary treatments for PCa were included in the analysis. All-cause mortality and prostate cancer-specific mortality (PCSM) were reported. Hazard ratios (HRs) and 95% confidence intervals (CIs) estimating the risks of death and of receiving secondary cancer treatment were generated by Cox hazard models. RESULTS: In patients aged ≤54, 55-59, and 60-69 years, about 60% of them in each group were classified into the high-risk, very high-risk, or metastatic group. However, young patients ≤54 years had a higher risk of PCSM than patients aged 60-69 years (HR = 1.22; 95% CI = 1.10-1.49). This trend of an increased risk in PCSM remained for high-risk, very high-risk, or metastatic patients (HR = 1.24; 95% CI = 1.01-1.51), but not in low- or intermediate-risk patients. Besides, young patients diagnosed with high-risk diseases had the highest risk of receiving secondary cancer treatment within 180 days after completing primary treatment among all age groups (HR = 1.32; 95% CI = 1.07-1.63). CONCLUSIONS: PCa arising in young patients ≤54 years of age, especially those with a high risk or metastatic form, might be more aggressive than that in other age groups.

Loco-regional deep hyperthermia combined with intravesical Mitomycin instillation reduces the recurrence of non-muscle invasive papillary bladder cancer.

OBJECTIVES: To compare the therapeutic effects of locoregional deep hyperthermia combined with intravesical chemotherapy with those of intravesical chemotherapy alone in patients with intermediate-/high-risk non-muscle invasive bladder cancer (NMIBC). To evaluate the impact of thermal dose in hyperthermia treatment. METHODS: We analyzed data retrieved from the medical records of patients with intermediate-/high-risk NMIBC treated with intravesical mitomycin (IM group) or locoregional deep hyperthermia combined with intravesical mitomycin (CHT group) at a single tertiary care hospital between May 2016 and June 2019. The primary and secondary endpoints were the recurrence-free survival rate and progression-free survival rate, respectively. Thermal dose was evaluated and adverse events were also recorded. RESULTS: In total, 43 patients (CHT: 18 patients, IM: 25 patients) were enrolled. The median follow-up durations were 14 and 23 months, respectively. The recurrence rate at 12 months was significantly lower in the CHT group than in the IM group (11.1% vs. 44%, p = .048); this trend persisted at 24 months (CHT: 11.1%, IM: 48%; p = .027). The recurrence-free survival was also significantly higher in the CHT group than in the IM group (p = .028). No tumor recurrence was noted in patients who received a thermal dose of ≥4 CEM43. All adverse events were well tolerated, and there was no treatment-related mortality. CONCLUSIONS: Intravesical chemotherapy combined with locoregional deep hyperthermia for intermediate-/high-risk papillary NMIBC can significantly decrease the recurrence rate relative to that observed after intravesical chemotherapy alone.

Clinical Experience of Steroid Switch from Prednisone to Dexamethasone in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone Acetate.

OBJECTIVE: To evaluate the therapeutic efficacy of a steroid switch from prednisone to dexamethasone in Asians with metastatic castration-resistant prostate cancer (mCRPC) that progressed after docetaxel chemotherapy. METHODS: This study included postdocetaxel patients with mCRPC treated with abiraterone acetate combined with prednisone (AA + P) who had experienced prostate-specific antigen (PSA) progression. All patients underwent a steroid switch from prednisone (10 mg/day) to dexamethasone (1 mg/day). The PSA level and clinical symptoms were recorded. Moreover, follow-up was conducted until patients were either lost to follow-up or death. RESULTS: This study included 11 patients from a single center in Taiwan. The median follow-up time starting from AA + P treatment was 19.47 months. Seven patients (63.64%) had >30% PSA decline, and 6 patients (54.55%) had >50% PSA decline. The median percentage of PSA decline was 83.6%. The median time until PSA progression after the steroid switch was 11.38 months. No adverse events greater than grade 3 were noted. CONCLUSIONS: Steroid switching is a feasible and effective therapy in docetaxel-treated Asian patients with mCRPC.

Prostatic Schwannoma Presenting with Prostate-specific Antigen Elevation: A Case Report.

Introduction: Schwannoma of the male genital system is very uncommon and is mostly treated by surgery. However, prostatic schwannoma presenting with elevated prostate-specific antigen (PSA) level and treated conservatively are extremely rare. Case presentation: Herein, we present a rare case of a prostatic schwannoma in a 65-year-old man who initially presented with an elevated PSA level. Digital rectal examination revealed an enlarged prostate with a palpable hard nodule on the left side. Transrectal ultrasonography revealed an enlarged prostate with a well-defined homogeneously hypoechoic nodule in the left peripheral lobe. Biopsy was done, and histopathology revealed a prostatic schwannoma. Conservative treatment with regular image follow-up was done per the patient's preference. Mild PSA progression but no worsening of symptoms was found in 6 years of follow-up. Conclusions: PSA elevation could be a rare presentation of prostatic schwannoma. Treatment options other than surgery, such as conservative treatment with close observation, could be feasible for these rare tumors and long-term survivorship can be achieved.

Hyperlipidemia patients with long-term statin treatment are associated with a reduced risk of progression of benign prostatic enlargement.

OBJECTIVE: To evaluate the impacts of statin treatment on the risk of benign prostatic enlargement (BPE) progression in hyperlipidemia patients. METHODS: Newly diagnosed hyperlipidemia patients (n = 7961), identified from Taiwan's National Health Insurance Research Database, were divided into four statin cohorts (statin use >365 days, n = 1604; statin use 181-365 days, n = 813; statin use 91-180 days, n = 739; and statin use 31-90 days, n = 713) and one control cohort (cohort that used no statins, n = 4092). Study endpoint was occurrence of BPE progression (BPE diagnosis plus receiving BPE-related medications or surgery). Relative risks of BPE progression in the statin cohorts compared to the control cohort were analyzed. RESULTS: Multivariable Cox proportional hazards regression analyses demonstrated that BPE progression risk in the cohort used statins for >365 days was significantly lower than the control cohort (adjusted hazard ratio: 0.70, 95% confidence interval: 0.58 ∼ 0.85, p < .001). However, BPE progression risks of the other three statin cohorts did not significantly differ from the control cohort. Trend analysis revealed that the effects of statin treatment on decreasing BPE progression risk were significantly related to statin treatment duration (p = .001). CONCLUSIONS: Hyperlipidemia patients with long-term statin treatment (more than 365 days) are associated with a reduced risk of BPE progression.

Magnesium Sulfate Mitigates the Progression of Monocrotaline Pulmonary Hypertension in Rats.

We investigated whether magnesium sulfate (MgSO4) mitigated pulmonary hypertension progression in rats. Pulmonary hypertension was induced by a single intraperitoneal injection of monocrotaline (60 mg/kg). MgSO4 (100 mg/kg) was intraperitoneally administered daily for 3 weeks, from the seventh day after monocrotaline injection. Adult male rats were randomized into monocrotaline (MCT) or monocrotaline plus MgSO4 (MM) groups (n = 15 per group); control groups were maintained simultaneously. For analysis, surviving rats were euthanized on the 28th day after receiving monocrotaline. The survival rate was higher in the MM group than in the MCT group (100% versus 73.3%, p = 0.043). Levels of pulmonary artery wall thickening, α-smooth muscle actin upregulation, right ventricular systolic pressure increase, and right ventricular hypertrophy were lower in the MM group than in the MCT group (all p < 0.05). Levels of lipid peroxidation, mitochondrial injury, inflammasomes and cytokine upregulation, and apoptosis in the lungs and right ventricle were lower in the MM group than in the MCT group (all p < 0.05). Notably, the mitigation effects of MgSO4 on pulmonary artery wall thickening and right ventricular hypertrophy were counteracted by exogenous calcium chloride. In conclusion, MgSO4 mitigates pulmonary hypertension progression, possibly by antagonizing calcium.

Testicular mixed germ cell tumor presenting with seizure as the initial symptom: a case report and literature review.

Most patients with testicular germ cell tumor present with a painless scrotal mass. We report a 19-year-old patient who presented with neurological complains. Rapid clinical progression to coma was noted during the staging work up. A diagnosis of testicular mixed germ cell tumor with multiorgan metastasis (lymph node, lung, liver and brain) was made. Patients with brain metastasis should receive chemotherapy alone or combined with surgery or radiotherapy. Because the clinical symptoms deteriorated quickly, surgery was used upfront followed by chemotherapy and radiotherapy for the brain tumor. After the first stage of treatment, the clinical symptoms, tumor markers and imaging findings were improved. The residual brain tumor was eliminated by chemotherapy, and only sparse degenerated tumor cells were noted in the brain tissue. Longer follow up is required to assess the impact of our treatment strategy.

Hyperlipidemia is associated with an increased risk of clinical benign prostatic hyperplasia.

BACKGROUND: A high fat diet is associated with risk of benign prostatic hyperplasia (BPH). However, whether hyperlipidemia is associated with BPH remains unclear. This population-based cohort study elucidated whether hyperlipidemia is associated with an increased risk of BPH. METHODS: We used a new-exposure design and analyzed data retrieved from the Taiwan National Health Insurance Database between January 1, 2000 and December 31, 2013. The cohort of men with newly diagnosed hyperlipidemia and the age- and index-date-matched (1:3) nonhyperlipidemia cohort were tracked for incidence of BPH during a 1- to 14-year follow-up. Diagnosis of BPH using the International Classification of Diseases, Ninth Revision, Clinical Modification codes, and the occurrence of BPH diagnosis plus the use of alpha-blockers or 5-alpha reductase inhibitors or receipt of transurethral resection of the prostate were the primary and secondary endpoints, respectively. The confounders in this study were diabetes mellitus, hypertension, coronary heart disease, obesity, liver cirrhosis, nonsteroidal anti-inflammatory drugs, metformin, aspirin, and number of urologist visits. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a multivariate Cox proportional hazards regression model adjusted for the propensity score. RESULTS: A total of 35 860 subjects (aged 40-99 years)-including the hyperlipidemia cohort (n = 8,965) and nonhyperlipidemia cohort (n = 26 895)-were identified. Our data revealed that the hyperlipidemia cohort had significantly higher incidences of developing BPH (24.6% vs 12.3%, P < 0.001) and treated BPH (13% vs 5.7%, P < 0.001) compared with the nonhyperlipidemia cohort. The risk of developing BPH in the hyperlipidemia cohort was significantly higher than that in the nonhyperlipidemia cohort (HR = 1.73, 95% CI = 1.63-1.83, P < 0.001) after adjustment for the propensity score. CONCLUSIONS: Hyperlipidemia is associated with an increased risk of clinical BPH.

FTY720 inhibits germ cell apoptosis in testicular torsion/detorsion.

BACKGROUND: Testicular torsion/detorsion (T/D) can induce germ cells apoptosis, which may lead to impairment of spermatogenesis. FTY720, an agonist of the sphingosine-1-phosphate receptor 1 (S1PR1), inhibits apoptosis in ischemic stroke. We examined whether FTY720 could mitigate germ cell apoptosis in testicular T/D rats. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were allocated to receive testicular T/D (the T/D group), T/D plus FTY720 (the T/D-FTY group), or T/D plus FTY720 plus the potent S1PR1 antagonist VPC23019 (the T/D-FTY-VPC group; n = 6 in each group). Sham control groups were run simultaneously. At 24 h after detorsion, rats were euthanized. RESULTS: Our data revealed that, in the ipsilateral twisted testes, sperm counts and expression of the S1PR1 of the T/D and the T/D-FTY-VPC groups were significantly lower than those of the T/D-FTY group (all P < 0.001). In contrast, signals of apoptotic cells stained by terminal deoxynucleotidyl transferase dUTP nick end labeling and the proapoptotic protein cleaved caspase-3 of the T/D, and the T/D-FTY-VPC groups were significantly stronger than those of the T/D-FTY group. Moreover, the terminal deoxynucleotidyl transferase dUTP nick end labeling signals mainly localized to germ cells. CONCLUSIONS: FTY720 could mitigate testicular T/D-induced germ cell apoptosis, and the mechanisms may involve the S1PR1.

FTY720 mitigates torsion/detorsion-induced testicular injury in rats.

BACKGROUND: FTY720, a sphingosine-1-phosphate (S1P) receptor agonist, possesses potent anti-inflammation capacity. We evaluated the therapeutic potentials of FTY720 against testicular injury induced by testicular torsion and/or detorsion (T/D). MATERIALS AND METHODS: Young adult male Sprague-Dawley rats were allocated to receive T/D (the T/D group) and T/D plus FTY720 (4 mg/kg, the T/D-FTY group, n = 6 in each group). To investigate the possible roles of the S1P receptors, another group of rats received T/D plus FTY720 plus the potent S1P receptor antagonist VPC23019 (1 mg/kg, the T/D-FTY-VPC group, n = 6). FTY720 was administered immediately before testicular detorsion, and VPC23019 was administered 30 min before FTY720. Another set of rats that received sham operation, immediately followed by injection of normal saline, FTY720, or FTY720 plus VPC23019, served as control groups. Sham control groups were run simultaneously. After euthanization, levels of testicular injury were measured. RESULTS: Histologic findings revealed severe testicular injury changes in both the T/D and T/D-FTY-VPC groups and moderate testicular injury changes in the T/D-FTY group. In addition, malondialdehyde activity (oxidative status), concentration of interleukin-1ß (inflammation index), myeloperoxidase activity (neutrophil infiltration index), and wet-to-dry weight ratio (tissue edema index) of both the T/D and T/D-FTY-VPC groups were significantly higher than those of the T/D-FTY group. These data confirmed the protective effects of FTY720 against testicular T/D. Moreover, antagonizing the S1P receptors could reverse the protective effects of FTY720. CONCLUSIONS: FTY720 significantly mitigated testicular injury induced by testicular T/D. The mechanisms may involve activating the S1P receptors.

Therapeutic Effects of Engineered Exosomes from RAW264.7 Cells Overexpressing hsa-let-7i-5p against Sepsis in Mice-A Comparative Study with Human Placenta-Derived Mesenchymal Stem Cell Exosomes.

This study compared the therapeutic effects of engineered exosomes derived from RAW264.7 cells overexpressing hsa-let-7i-5p (engineered exosomes) to exosomes from human placenta-derived mesenchymal stem cells (hpMSC exosomes) against sepsis-induced acute lung injury. Adult male C57BL/6 mice were divided into lipopolysaccharide (LPS), LPS plus engineered exosome (LEExo), or LPS plus hpMSC exosome (LMExo) groups, alongside control groups. The results showed that lung injury scores (based on pathohistological characteristics) and the levels of lung function alterations, tissue edema, and leukocyte infiltration in LEExo and LMExo groups were comparable and significantly lower than in the LPS group (all p < 0.05). Furthermore, the levels of inflammation (nuclear factor-κB activation, cytokine upregulation), macrophage activation (hypoxia-inducible factor-1α activation, M1 phase polarization), oxidation, and apoptosis were diminished in LEExo and LMExo groups compared to the LPS group (all p < 0.05). Inhibition of hsa-let-7i-5p attenuated the therapeutic effects of both engineered and hpMSC exosomes. These findings underscore the potent therapeutic capacity of engineered exosomes enriched with hsa-let-7i-5p and their potential as an alternative to hpMSC exosomes for sepsis treatment. Continued research into the mechanisms of action and optimization of engineered exosomes could pave the way for their future clinical application.

Robot-Assisted Radical Prostatectomy by the Hugo Robotic-Assisted Surgery (RAS) System and the da Vinci System: A Comparison between the Two Platforms.

OBJECTIVE: In a previous study, we proved that an experienced urologist is more likely to adapt to the Hugo RAS system. Based on this, we further examine various parameters in this study. Parameters included in this study consisted of console time, functional outcomes, and oncological outcomes. MATERIALS AND METHODS: A total of 60 patients who underwent robot-assisted radical prostatectomy (RARP) performed by a single surgeon using the da Vinci (DV) system (n = 30) or the Hugo RAS system (n = 30) between March 2023 and August 2023 were included in the analysis. The intraoperative operative time was categorized into vesicourethral anastomosis time and overall console time. Functional and oncological outcomes were documented at the 1st and 3rd postoperative months. Parametric and non-parametric methods were adopted after checking skewness and kurtosis, and an α value of 5% was used to determine the significance. RESULTS: The vesicourethral anastomosis time was significantly lengthened (Hedge's g: 0.87; 95% confidence interval (CI): 0.34-1.39; J factor = 0.987). However, the overall console time was not affected. The functional (postoperative 3rd month: p = 0.130) and oncological outcomes (postoperative 3rd month: p = 0.103) were not significantly different. We also found that the adverse effect on surgical specimens and positive surgical margins was not affected (p = 0.552). CONCLUSION: During the process of adaptation, although intricate motions (such as the vesicourethral anastomosis time) would be lengthened, the overall console time would not change remarkably. In this process, the functional and oncological outcomes would not be compromised. This encourages urologists to adopt the Hugo RAS system in RARP if they have previous experiences of using the DV system, since their trifecta advantage would not be compromised.

Unusual presentation of cutaneous metastasis from bladder urothelial carcinoma.

Cutaneous metastases from urothelial carcinoma of the bladder are a rare disease. In previous reports, the most common metastatic cutaneous lesions were non-tender nodules on the abdominal skin. We report a patient with bladder urothelial carcinoma with cutaneous metastases initially presenting as right leg and suprapubic lymphedema. Bladder tumor was the incidental finding by magnetic resonance venography. Urothelial carcinoma (clinical stage IV) was diagnosed, and chemotherapy was performed. Extensive painful erythematous plaques with an erysipelas-like appearance located on the suprapubic area, chest and abdomen were noted, and cutaneous metastases were confirmed by histopathology. Subsequently, extensive scrotal and prepuce ulcerative changes developed. This paper reports a rare case of extensive cutaneous metastasis of bladder urothelial carcinoma who presented an interesting clinical course.

Exosomes from Human Placenta Choriodecidual Membrane-Derived Mesenchymal Stem Cells Mitigate Endoplasmic Reticulum Stress, Inflammation, and Lung Injury in Lipopolysaccharide-Treated Obese Mice.

Endoplasmic reticulum (ER) stress mediates the effects of obesity on aggravating sepsis-induced lung injury. We investigated whether exosomes from human placenta choriodecidual membrane-derived mesenchymal stem cells (pcMSCs) can mitigate pulmonary ER stress, lung injury, and the mechanisms of inflammation, oxidation, and apoptosis in lipopolysaccharide-treated obese mice. Diet-induced obese (DIO) mice (adult male C57BL/6J mice fed with a 12-week high-fat diet) received lipopolysaccharide (10 mg/kg, i.p.; DIOLPS group) or lipopolysaccharide plus exosomes (1 × 108 particles/mouse, i.p.; DIOLPSExo group). Our data demonstrated lower levels of ER stress (upregulation of glucose-regulated protein 78, phosphorylated eukaryotic initiation factor 2α, and C/EBP homologous protein; p = 0.038, <0.001, and <0.001, respectively), inflammation (activation of nuclear factor-kB, hypoxia-inducible factor-1α, macrophages, and NLR family pyrin domain containing 3; upregulation of tumor necrosis factor-α, interleukin-1ß, and interleukin-6; p = 0.03, <0.001, <0.001, <0.001, <0.001, <0.001, and <0.001, respectively), lipid peroxidation (p < 0.001), and apoptosis (DNA fragmentation, p = 0.003) in lung tissues, as well as lower lung injury level (decreases in tidal volume, peak inspiratory flow, and end expiratory volume; increases in resistance, injury score, and tissue water content; p < 0.001, <0.001, <0.001, <0.001, <0.001, and =0.002, respectively) in the DIOLPSExo group than in the DIOLPS group. In conclusion, exosomes from human pcMSCs mitigate pulmonary ER stress, inflammation, oxidation, apoptosis, and lung injury in lipopolysaccharide-treated obese mice.

Tumor Necrosis Factor-α Mediates Lung Injury in the Early Phase of Endotoxemia.

Endotoxemia induces lung injury. We assessed the therapeutic efficacy between triple cytokine (tumor necrosis factor-α [TNF-α], interleukin-1ß [IL-1ß], and IL-6) inhibition (mediated by KCF18 peptide) and single cytokine (TNF-α) inhibition (mediated by SEM18 peptide) on alleviating lung injury in the early phase of endotoxemia. Mice receiving endotoxin (Endo group), endotoxin plus KCF18 (EKCF group), or endotoxin plus SEM18 (ESEM) were monitored and euthanized at 24 h after endotoxin. Our data demonstrated altered lung function (decreases in tidal volume, minute ventilation, and dynamic compliance; and by contrast, increases in airway resistance and end expiration work) and histology (increases in injury scores, leukocyte infiltration, vascular permeability, and tissue water content) in the Endo group with significant protection observed in the EKCF and ESEM groups (all p < 0.05). Levels of inflammation (macrophage activation and cytokine upregulations), oxidation (lipid peroxidation), necroptosis, pyroptosis, and apoptosis in EKCF and ESEM groups were comparable and all were significantly lower than in the Endo group (all p < 0.05). These data demonstrate that single cytokine TNF-α inhibition can achieve therapeutic effects similar to triple cytokines TNF-α, IL-1ß, and IL-6 inhibition on alleviating endotoxin-induced lung injury, indicating that TNF-α is the major cytokine in mediating lung injury in the early phase of endotoxemia.

Gross hematuria and IgA nephropathy flare-up following the first dose of Moderna vaccine: A case report.

BACKGROUND: Since the mass vaccination for COVID-19, several case reports indicated the risk of autoimmune disease flare-ups after the vaccination. Among them, COVID-19 vaccine-induced glomerular diseases have drawn attention worldwide. The cases demonstrating the association between the mRNA vaccine and IgA nephropathy (IgAN) exacerbation had been noticed. Mostly mentioned, the flare-ups usually occurred after the second dose. METHODS: We present a Taiwanese female with IgAN who developed gross hematuria within only six hours after the first dose of the Moderna vaccine. RESULTS: Six hours after the first dose of Moderna vaccine on 8 June 2021, the patient developed gross hematuria and significantly decreased urine output. All symptoms resolved spontaneously on the fifth day after the vaccination without any intervention. On the fourth day after the vaccination, the patient were able to back to her original condition. CONCLUSION: This was an intriguing case of IgAN flare-up following the first dose of mRNA-based COVID-19 vaccination.

High-Fructose/High-Fat Diet Downregulates the Hepatic Mitochondrial Oxidative Phosphorylation Pathway in Mice Compared with High-Fat Diet Alone.

Both high-fat diet (HFD) alone and high-fructose plus HFD (HFr/HFD) cause diet-induced non-alcoholic fatty liver disease in murine models. However, the mechanisms underlying their impacts on inducing different levels of liver injury are yet to be elucidated. This study employed a proteomic approach to elucidate further on this issue. Adult male C57BL/6J mice were allocated to the HFD or the HFr/HFD group. After feeding for 12 weeks, all mice were euthanized and samples were collected. The proteomic profiles in liver tissues were analyzed using liquid chromatography-tandem mass spectrometry followed by canonical pathway analysis. We demonstrated that the mitochondrial oxidative phosphorylation (OXPHOS) pathway was the most significantly downregulated canonical pathway in the HFr/HFD group when compared with the HFD group. Within the OXPHOS pathway, the HFr/HFD group demonstrated significant downregulation of complexes I and III and significant upregulation of complex IV when compared with the HFD group. Moreover, the HFr/HFD group had lower protein levels of NADH: ubiquinone oxidoreductase subunits S3, S6, A5, and A12 in complex I (p < 0.001, =0.03, <0.001, and <0.001, respectively), lower protein level of cytochrome C in complex III (p < 0.001), and higher protein level of cytochrome C oxidase subunit 2 in complex IV (p = 0.002), when compared with the HFD group. To summarize, we have demonstrated that the hepatic mitochondrial OXPHOS pathway is significantly downregulated in long-term HFr/HFD feeding when compared with long-term HFD feeding. These data support the concept that the hepatic mitochondrial OXPHOS pathway should be involved in mediating the effects of HFr/HFD on inducing more severe liver injury than HFD alone.