Endothelial cell dynamics in sepsis-induced acute lung injury and acute respiratory distress syndrome: pathogenesis and therapeutic implications.

Sepsis, a prevalent critical condition in clinics, continues to be the leading cause of death from infections and a global healthcare issue. Among the organs susceptible to the harmful effects of sepsis, the lungs are notably the most frequently affected. Consequently, patients with sepsis are predisposed to developing acute lung injury (ALI), and in severe cases, acute respiratory distress syndrome (ARDS). Nevertheless, the precise mechanisms associated with the onset of ALI/ARDS remain elusive. In recent years, there has been a growing emphasis on the role of endothelial cells (ECs), a cell type integral to lung barrier function, and their interactions with various stromal cells in sepsis-induced ALI/ARDS. In this comprehensive review, we summarize the involvement of endothelial cells and their intricate interplay with immune cells and stromal cells, including pulmonary epithelial cells and fibroblasts, in the pathogenesis of sepsis-induced ALI/ARDS, with particular emphasis placed on discussing the several pivotal pathways implicated in this process. Furthermore, we discuss the potential therapeutic interventions for modulating the functions of endothelial cells, their interactions with immune cells and stromal cells, and relevant pathways associated with ALI/ARDS to present a potential therapeutic strategy for managing sepsis and sepsis-induced ALI/ARDS.

A novel trauma induced urethral stricture in rat model.

Urethral stricture (US) is a longstanding disease, while there has not existed a suitable animal model to mimic the condition. We aimed to establish a trauma-induced US animal model to simulate this clinical scenario. A total of 30 rats were equally distributed into two groups, sham and US group. All rats were anesthetized with isoflurane and undergone cystostomy. In the US group, a 2 mm incision was made in the urethra and sutured to induce US. The sham group only make a skin incision on the ventral side of the anterior urethra. 4 weeks later, ultrasound and cystourethrography were performed to evaluate the degree of urethral stricture, pathological examinations were carried out to evaluate the degree of fibrosis. Urodynamic evaluation and mechanical tissue testing were performed to evaluate the bladder function and urethral tissue stiffness. The results showed that the urethral mucosa was disrupted and urethral lumen was stenosed in the US group. Additionally, the US group showed elevated bladder pressure, prolonged micturition intervals and increased tissue stiffness. In conclusion, the rat urethral stricture model induced by trauma provides a closer representation of the real clinical scenario. This model will significantly contribute to advancing research on the mechanisms underlying traumatic urethral stricture.

Extracellular matrix stiffness aggravates urethral stricture through Igfbp3/Smad pathway.

Urethral stricture refers to the narrowing of the urethral lumen. While previous studies have hinted at inflammation as the initial driver of this condition, the reasons and mechanisms behind its progression remain largely unknown. By Atomic force microscope (AFM), researchers measured the matrix stiffness of urethra to be 5.23 ± 0.37 kPa for normal tissue and 41.59 ± 2.48 kPa for stricture urethral scar. Similar results were observed in rat urethral stricture models, where the matrix stiffness of normal urethra was 4.29 ± 0.82 kPa, while 32.94 ± 7.12 kPa for urethral stricture scar. Notably, the matrix stiffness increased in rat models over time. To further investigate, polyacrylamide hydrogels were employed to mimic different levels of stiffness for normal and stricture condition. Interestingly, higher matrix stiffness led to an increased fibroblast-to-myofibroblast transition (FMT) in rat urethral fibroblasts, indicated by enhanced expression of α-SMA and Collagen I, as well as changing in the morphology of fibroblast. RNA-seq analysis suggested that Igfbp3/Smads might regulate the progressive FMT in urethral stricture. In the experiment where the expression of Igfbp3 was inhibited, increasing matrix stiffness lose the potential to stimulate FMT progression and the expression of p-Smad2/3 decreased. On the contrary, overexpression of Igfbp3 promoted the process of FMT in urethral fibroblasts. In conclusion, Igfbp3/Smad pathway appeared to be involved in the progression of urethral fibrosis. This finding suggested that Igfbp3/Smad might be an promising target for future research and treatment in this filed.

Inhibition of PPARγ by BZ26, a GW9662 derivate, attenuated obesity-related breast cancer progression by inhibiting the reprogramming of mature adipocytes into to cancer associate adipocyte-like cells.

Obesity has been associated with the development of 13 different types of cancers, including breast cancer. Evidence has indicated that cancer-associated adipocytes promote the proliferation, invasion, and metastasis of cancer. However, the mechanisms that link CAAs to the progression of obesity-related cancer are still unknown. Here, we found the mature adipocytes in the visceral fat of HFD-fed mice have a CAAs phenotype but the stromal vascular fraction of the visceral fat has not. Importantly, we found the derivate of the potent PPARγ antagonist GW9662, BZ26 inhibited the reprogramming of mature adipocytes in the visceral fat of HFD-fed mice into CAA-like cells and inhibited the proliferation and invasion of obesity-related breast cancer. Further study found that it mediated the browning of visceral, subcutaneous and perirenal fat and attenuated inflammation of adipose tissue and metabolic disorders. For the mechanism, we found that BZ26 bound and inhibited PPARγ by acting as a new modulator. Therefore, BZ26 serves as a novel modulator of PPARγ activity, that is, capable of inhibiting obesity-related breast cancer progression by inhibiting of CAA-like cell formation, suggesting that inhibiting the reprogramming of mature adipocytes into CAAs or CAA-like cells may be a potential therapeutic strategy for obesity-related cancer treatment.

Anesthesia Analysis of Compound Lidocaine Cream Alone in Adult Male Device-Assisted Circumcision.

OBJECTIVE: to evaluate the anesthetic effect among adult male patients with the single use of compound lidocaine cream in device-assisted circumcision, hoping to provide an anesthetic method for the simplification of the surgical process. METHODS: Male adult patients undergoing device-assisted circumcision through prepuce local anesthesia using lidocaine cream in Xiangya Hospital of Central South University from December 2020 to August 2021 were selected. According to different age groups and different surgical procedures, the anesthetic effect of compound lidocaine cream was analyzed considering the aspects of anesthetic cost, anesthetic time, anesthetic duration, anesthetic effect, anesthetic side effects and anesthetic satisfaction. RESULTS: In the study, 99.1% of 649 patients needed only 1 application of compound lidocaine cream to complete the operation. The time taken for anesthesia was short; the whole anesthesia process only required approximately 2-5 min. However, for patients with severe phimosis, the time to complete the anesthesia procedure was correspondingly longer. The pain degree caused by anesthesia was low, and the patients with a pain score of ≤3 points accounted for 96.7%. The anesthetic effect lasted for a sufficiently long period, and the time of algesia recovery from local anesthesia was almost 1 h after surgery. The anesthesia effect was sufficient, and patients with an intraoperative pain score of ≤3 accounted for 98.7%, which could meet the surgical requirements. There were few side effects of the anesthesia. The overwhelming majority of patients were pleased with the anesthesia, and 98.9% of patients had an anesthesia satisfaction score of ≥7. CONCLUSION: The compound lidocaine cream, as a local anesthetic, is safe and effective for most adult male device-assisted circumcisions. More useful information needs to be corroborated by more advanced evidence, especially for severe phimosis.

Venous Thromboembolism and Bleeding after Transurethral Resection of the Prostate (TURP) in Patients with Preoperative Antithrombotic Therapy: A Single-Center Study from a Tertiary Hospital in China.

BACKGROUND: Venous thromboembolism (VTE) and postoperative hemorrhage are unavoidable complications of transurethral resection of the prostate (TURP). At present, more and more patients with benign prostate hyperplasia (BPH) need long-term antithrombotic therapy before operation due to cardiovascular diseases or cerebrovascular diseases. The purpose of this study was to investigate the effect of preoperative antithrombotic therapy history on lower extremity VTE and bleeding after TURP. METHODS: Patients who underwent TURP in the Department of Urology, Xiangya Hospital, Central South University, from January 2017 to December 2021 and took antithrombotic drugs before operation were retrospectively analyzed. The baseline data of patients were collected, including age, prostate volume, preoperative International Prostate Symptom Score (IPSS), complications, surgical history within one month, indications of preoperative antithrombotic drugs, drug types, medication duration, etc. Main outcome measures included venous thromboembolism after TURP, intraoperative and postoperative bleeding, and perioperative blood transfusion. Secondary outcome measures included operation duration and postoperative hospitalization days, the duration of stopping antithrombotic drugs before operation, the recovery time of antithrombotic drugs after operation, the condition of lower limbs within 3 months after operation, major adverse cardiac events (MACEs), and cerebrovascular complications and death. RESULTS: A total of 31 patients after TURP with a long preoperative history of antithrombotic drugs were included in this study. Six patients (19.4%) developed superficial venous thrombosis (SVT) postoperatively. Four of these patients progressed to deep vein thrombosis (DVT) without pulmonary thromboembolism (PE). Only one patient underwent extra bladder irrigation due to blockage of their urinary catheter by a blood clot postoperatively. The symptoms of hematuria mostly disappeared within one month postoperatively and lasted for up to three months postoperatively. No blood transfusion, surgical intervention to stop bleeding, lower limb discomfort such as swelling, MACEs, cerebrovascular complications, or death occurred in all patients within three months after surgery. CONCLUSION: Short-term preoperative discontinuation may help patients with antithrombotic therapy to obtain a relatively safe opportunity for TURP surgery after professional evaluation of perioperative conditions. The risks of perioperative bleeding, VTE, and serious cardiovascular and cerebrovascular complications are relatively controllable. It is essential for urologists to pay more attention to the perioperative management of these patients. However, further high-quality research results are needed for more powerful verification.

Prognostic values of the immune microenvironment-related non-coding RNA IGF2BP2-AS1 in bladder cancer.

Bladder cancer can range from noninvasive to invasive tumors. When non-muscle invasive bladder cancer (NMIBC) recurs, patients could endure long-term invasive malignancies with a high disease-specific death rate. Immune escape frequently results in tumor development, metastases, unfavorable prognosis, and failure of immunotherapy. Based on the median immune score, this study used ESTIMATE scores to evaluate 411 bladder cancer cases from TCGA-BLCA. Two hundred two ncRNAs were differentially expressed in two groups, where 29 candidates appeared to be associated with the overall survival of bladder cancer patients. LASSO algorithm was performed to establish the risk score model of 13-ncRNA. Risk scores were computed for cases in the training set, validation set, and TCGA-BLCA set; Poor prognosis in cases with higher risk scores was based on the training set, validating set, and TCGA-BLCA set. Among the 13 ncRNAs, IGF2BP2-AS1, MAGF-AS1, ARHGAP5-AS1, and LINC00942 were significantly correlated with the overall survival of bladder cancer patients. Pearson's correlation analysis based on TCGA-BLCA identified 2093, 3107, 386, and 936 mRNAs co-expressed with IGF2BP2-AS1, MAGF-AS1, ARHGAP5-AS1, and LINC00942, respectively. Conclusively, the 13 ncRNA signature exhibited a feasible predictive prognostic value for bladder cancer patients. IGF2BP2-AS1 expression was higher in bladder cancer tissues and significantly correlated to immune-related factors, suggesting that IGF2BP2-AS1 represents a promising immune-related target for treating bladder cancer patients.

Comparison of bladder autoaugmentation by transurethral vesicomyotomy and hydrodistention for ketamine cystitis.

BACKGROUND: To illustrate the bladder autoaugmentation by transurethral vesicomyotomy (BATV) and compare the efficacy and safety of BATV to bladder hydrodistention (BH) for managing ketamine cystitis (KC). METHODS: We retrospectively analyzed clinical data for 53 patients with KC who received surgical intervention between 2014 and 2019 at our hospital. Of these, 41 (77.4%) underwent BH and 12 (22.6%) were subjected to BATV, with a minimum of 1-year follow-up. These groups were compared with reference to urodynamic parameters, subjective symptom scores as well as all complications. RESULTS: Both groups were matched in age, addiction time, preoperative urodynamic parameters, postvoid residual urinary volume (PVR), and symptom scores. All urodynamic parameters including maximum cystometric capacity (MCC), maximum detrusor pressure (Pdet max), compliance, maximum urinary flow rate (Qmax) and symptom scores had improved significantly in two groups whether at 3 or 12 months. Moreover, the MCC was significantly increased after BATV than BH, at a mean [standard deviation (SD)] of 281.0 (25.7) vs. 213.5 (35.6) mL (P<0.001) at 12-month follow-up. The Qmax and the Pelvic Pain and Urgency/Frequency (PUF) symptom score were still noted better in the BATV group at 3 months after surgery. Additionally, patients in both groups had similarly low rates of complications. CONCLUSIONS: BATV is superior to BH with increased bladder capacity and urodynamic outcomes, although showing equivalent in symptom relief and a similar rate of complications.

Incidence and Risk Factors of Venous Thromboembolism in Patients After Transurethral Resection of the Prostate (TURP).

OBJECTIVE: Venous thromboembolism (VTE) in patients following transurethral resection of the prostate (TURP) has been overlooked for many years. This research was aimed to investigate the incidence and risk factors of VTE in patients after TURP. METHODS: A total of 451 patients who underwent TURP between January 2017 and December 2020 were retrospectively analyzed. Clinical data of the patients were collected, such as basic demographic data, prostate volume, creatinine values, hemoglobin values, surgery duration, Caprini score, international prostate symptom score (IPSS), quality of life (QOL) score, plasma D-dimer levels, and so on. Univariate analysis and multivariate logistic regression were performed to identify the potential risk factors of VTE. Venous ultrasonography of lower extremities was performed routinely to detect VTE for patients after TURP. RESULTS: In total, 36 (8%) out of the 451 patients suffered from VTE. A total of 12 (2.7%) patients were confirmed with deep venous thrombosis (DVT). Two patients (0.4%) were identified with pulmonary embolism (PE). Twenty-two (4.9%) patients were suffered from superficial venous thrombosis. Furthermore, according to the results of multivariate stepwise logistic regression analysis, having a history of VTE (adjusted odds ratio [aOR] = 10.980, 95% CI = 2.265-53.223), complicated with postoperative bladder hematoma (aOR = 6.302, 95% CI = 2.265-17.532), D-dimer >1.25 mg/L (aOR = 4.402, 95% CI = 1.798-10.774), and age >65 (aOR = 3.106, 95% CI = 1.084-8.893) were independent risk factors of VTE after TURP. In addition, the nomogram prediction model is a useful auxiliary prevention tool of VTE. CONCLUSION: The incidence of VTE is severely underestimated in patients following TURP. A lot of asymptomatic VTEs have been overlooked. Early detection and diagnosis of VTE are essential. Nevertheless, further verifications based on the results of large-scaled studies are still needed.

Real-time highlight removal using intensity ratio.

In this paper, we propose an efficient method to separate the diffuse and specular reflection components from a single image. The method is built on the observation that, for diffuse pixels, the intensity ratios between the maximum values and range values (maximums minus minimums) are independent of surface geometry. The specular fractions of the image pixels can then be computed by using the intensity ratio. For textured surfaces, image pixels are classified into clusters by constructing a pseudo-chromaticity space, and the intensity ratio of each cluster is robustly estimated. Unlike existing techniques, the proposed method works in a pixel-wise manner, without specular pixel identification and any local interaction. Experimental results show that the proposed method runs 4× faster than the state of the art and produces improved accuracy in specular highlight removal.

Autofocus for multispectral camera using focus symmetry.

A multispectral camera acquires spectral color images with high fidelity by splitting the light spectrum into more than three bands. Because of the shift of focal length with wavelength, the focus of each channel should be mechanically adjusted in order to obtain sharp images. Because progressive adjustment is quite time consuming, the clear focus must be determined by using a limited number of images. This paper exploits the symmetry of focus measure distribution and proposes a simple yet efficient autofocus method. The focus measures are computed using first-order image derivatives, and the focus curve is obtained by spline interpolation. The optimal focus position, which maximizes the symmetry of the focus measure distribution, is then computed according to distance metrics. The effectiveness of the proposed method is validated in the multispectral camera system, and it is also applicable to relevant imaging systems.