Aloe-emodin relieves allergic contact dermatitis pruritus by inhibiting mast cell degranulation.

Urushiol-induced allergic contact dermatitis (ACD) is a chronic inflammatory skin disease in which skin barrier dysfunction leads to pruritus and eczematous lesions. ACD is triggered by immune imbalance. Aloe emodin is an anthraquinone derivative extracted from rhubarb, aloe and other traditional Chinese medicines. It has a wide range of pharmacological effects, including anti-inflammatory, anti-tumor, and anti-allergic effects. The purpose of our study was to demonstrate the effectiveness of aloe-emodin on urushiol-induced acute pruritus and allergic contact dermatitis. The results showed that urushiol could stimulate keratinocytes to release chemokines CXCL1, CXCL2, CCL2, TSLP, and TNF-α, which recruit or activate mast cells. Aloe-emodin treatment inhibited inflammatory-response-induced mast cell degranulation in skin lesions and suppressed the expression of inflammatory cytokines, such as interleukin-4, and interleukin-6. Therefore, the results indicate that aloe-emodin can improve urushiol-induced acute pruritus and allergic contact dermatitis in mice by inhibiting mast cell degranulation.

Dual-strategy engineered nickel phosphide for achieving efficient hydrazine-assisted hydrogen production in seawater.

Electrocatalytic hydrogen production in seawater to alleviate freshwater shortage pressures is promising, but is hindered by the sluggish oxygen evolution reaction and detrimental chloride electrochemistry. Herein, a dual strategy approach of Fe-doping and CeO2-decoration in nickel phosphide (Fe-Ni2P/CeO2) is rationally designed to achieve superior bifunctional catalytic performance for the hydrogen evolution reaction (HER) and hydrazine oxidation reaction (HzOR) in seawater. Notably, the two-electrode Fe-Ni2P/CeO2-based hybrid seawater electrolyzer realizes energy-efficient and chlorine-free hydrogen production with ultralow cell voltages of 0.051 and 0.597 V at 10 and 400 mA cm-2, which are significantly lower than those needed in the hydrazine-free seawater electrolyzer. Density functional theory calculations manifest that the combination of Fe doping and heterointerface construction between Fe-Ni2P and CeO2 can adjust the electronic structure of the Ni2P and optimize the water dissociation barrier and hydrogen adsorption free energy, leading to improvement of the intrinsic catalytic performance. This route affords a feasible solution for future large-scale hydrogen generation using abundant ocean water.

The efficacy and safety of ciprofol and propofol in patients undergoing colonoscopy: A double-blind, randomized, controlled trial.

STUDY OBJECTIVE: Propofol is a commonly utilized anesthetic for painless colonoscopy, but its usage is occasionally limited due to its potential side effects, including cardiopulmonary suppression and injection pain. To address this limitation, the novel compound ciprofol has been proposed as a possible alternative for propofol. This study sought to determine whether there are any differences in the safety and efficacy of propofol and ciprofol for painless colonoscopy. DESIGN: Randomized clinical trial. SETTING: Single-centre, class A tertiary hospital, November 2021 to November 2022. PATIENTS: Adult, American Society of Anesthesiologists Physical Status I to II and body mass index of 18 to 30 kg m-2 patients scheduled to undergo colonoscopy. INTERVENTIONS: Consecutive patients were randomly allocated in a 1:1 ratio to receive sedation for colonoscopy with ciprofol (group C) or propofol (group P). MEASUREMENTS: The primary outcome was the success rate of colonoscopy. The secondary outcomes were onset time of sedation, operation time, recovery time and discharge time, patients and endoscopists satisfaction, side effects (e.g. injection pain, myoclonus, drowsiness, dizziness, procedure recall, nausea and vomiting) and incidence rate of cardiopulmonary adverse events. MAIN RESULTS: No significant difference was found in the success rate of colonoscopy between the two groups (ciprofol 96.3% vs. propofol 97.6%; mean difference - 1.2%, 95% CI: -6.5% to 4.0%, P = 0.650). However, group C showed prolonged sedation (63.4 vs. 54.8 s, P < 0.001) and fully alert times (9 vs 8 min, P = 0.013), as well as reduced incidences of injection pain (0 vs. 40.2%, P < 0.001), respiratory depression (2.4% vs. 13.4%, P = 0.021) and hypotension (65.9% vs. 80.5%, P = 0.034). Patients satisfaction was also higher in Group C (10 vs 9, P < 0.001). CONCLUSIONS: Ciprofol can be used independently for colonoscopy. When comparing the sedation efficacy of ciprofol and propofol, a 0.4 mg kg-1 dose of ciprofol proved to be equal to a 2.0 mg kg-1 dose of propofol, with fewer side effects and greater patient satisfaction during the procedure.

[Application of iliac vein molding and stent implantation through the ipsilateral great saphenous vein approach in daytime treatment mode].

OBJECTIVE: To explore the feasibility and recent efficacy of iliac vein molding and stenting in daytime treatment mode in patients with iliac vein stenosis. METHODS: Medical records of iliac vein molding and stenting performed in the ipsilateral great saphenous vein approach conducted from February 2017 to March 2022 were retrospective reviewed. There were 21 cases, 6 males and 15 females. Age ranged from 37 to 79 years [(62.5 ± 10.2) years]. The stenosis in the 21 limbs simply involved the common iliac veins in 16 patients, 2 patients had the simple and external iliac veins, and both the total and external iliac veins in 3 patients. Both iliac vein molding and iliac vein stenting were performed through the ipsilateral great saphenous vein approach. The patients with simple iliac vein stenosis with great saphenous vein valve insufficiency also underwent radiofrequency closure of great saphenous vein and flexural vein sclerosis therapy simultaneously. Regular postoperative direct oral anticoagulants therapy and stress therapy were followed. All the patients were hospitalized for less than 24 h. RESULTS: All the 21 patients operations were successful (the success rate was 100%), without any intraoperative complications. Immediate postoperative complications were puncture point bleeding in 1 case. The bandage gauze was completely wet. The bleeding was stopped after 5min of recompression. All the patients were hospitalized for less than 24 h. Follow-up results: The 3-month follow-up rate after operation was 100%. Absolute effective 18 cases (18/21, 85.7%). Relatively effective(postmentation still after surgery, but with less extent) in 3 cases (3/21, 14.3%). The iliac vein stents were unobstructed, and the trunk of the great saphenous vein was well closed in the patients with great saphenous vein radiofrequency treatment. The 6-month follow-up rate after operation was 71.4%(15/21). Of these, 14 cases (14/15, 93.3%) were absolutely effective. Relatively effective(postmentation still after surgery, but with less extent) in 1 case (1/15, 6.7%). The iliac vein stents were no restenosis or obstruction, and the trunk of the great saphenous vein was well closed in the patients with great saphenous vein radiofrequency treatment. CONCLUSION: The interventional treatment technique of iliac vein stenosis is feasible in the daytime treatment mode, with clear advantages and satisfactory recent efficacy.

Combination of prostate volume and apparent diffusion coefficient can stratify patients with a PI-RADS score of 3 to reduce unnecessary prostate biopsies.

BACKGROUND: Nowadays, there are many patients who undergo unnecessary prostate biopsies after receiving a prostate imaging reporting and data system (PI-RADS) score of 3. Our purpose is to identify cutoff values of the prostate volume (PV) and minimum apparent diffusion coefficient (ADCmin) to stratify those patients to reduce unnecessary prostate biopsies. METHODS: Data from 224 qualified patients who received prostate biopsies from January 2019 to June 2023 were collected. The Mann-Whitney U test was used to compare non-normal distributed continuous variables, which were recorded as median (interquartile ranges). The correlation coefficients were calculated using Spearman's rank correlation analysis. Categorical variables are recorded by numbers (percentages) and compared by χ2 test. Both univariate and multivariate logistic regression analysis were used to determine the independent predictors. The receiver-operating characteristic curve and the area under the curve (AUC) were used to evaluate the diagnostic performance of clinical variables. RESULTS: Out of a total of 224 patients, 36 patients (16.07%) were diagnosed with clinically significant prostate cancer (csPCa), whereas 72 patients (32.14%) were diagnosed with any grade prostate cancer. The result of multivariate analysis demonstrated that the PV (p < 0.001, odds ratio [OR]: 0.952, 95% confidence interval [95% CI]: 0.927-0.978) and ADCmin (p < 0.01, OR: 0.993, 95% CI: 0.989-0.998) were the independent factors for predicting csPCa. The AUC values of the PV and ADCmin were 0.779 (95% CI: 0.718-0.831) and 0.799 (95% CI: 0.740-0.849), respectively, for diagnosing csPCa. After stratifying patients by PV and ADCmin, 24 patients (47.06%) with "PV < 55 mL and ADCmin < 685 µm2/s" were diagnosed with csPCa. However, only one patient (1.25%) with PV ≥ 55 mL and ADCmin ≥ 685 µm2/s were diagnosed with csPCa. CONCLUSIONS: In this study, we found the combination of PV and ADCmin can stratify patients with a PI-RADS score of 3 to reduce unnecessary prostate biopsies. These patients with "PV ≥ 55 mL and ADCmin ≥ 685 µm2/s" may safely avoid prostate biopsies.

Multivariate logistic regression analysis of the clinical factors influencing locally advanced prostate cancer.

Background: Locally advanced prostate cancer (PCa) carries a high risk of recurrence and metastasis after surgery, and the prognosis is poor. We explored the risk factors for locally advanced PCa among clinical factors (neutrophil: lymphocyte ratio, lymphocyte: monocyte ratio) and indicators of systemic inflammation [prostate-specific antigen (PSA) level, Gleason score, body mass index (BMI)] through retrospective evaluation of patients with PCa diagnosed at our center. The pathologic T stage was a key indicator of locally advanced PCa. Methods: Data from patients with pathologically confirmed PCa at our center from 1 January 2015 to 1 May 2020 were collected in strict accordance with inclusion and exclusion criteria. Clinical data were collected and the relationship between the indicators and the pathologic T stage was explored. First, Spearman rank correlation analysis was used to find the correlates of the pathologic T stage. Then, logistic ordered multiple regression analysis was used to identify independent risk factors. Finally, receiver operating characteristic (ROC) curves were used to assess the diagnostic accuracy for the T stage of PCa. Results: After rigorous screening, the data of 177 patients were obtained. Spearman correlation analysis showed that BMI, the PSA level, Gleason score, hypertension, N stage, and M stage were significantly correlated with the T stage (P<0.05), suggesting that these factors may be involved in locally advanced PCa. Analyses of ROC curves showed that the PSA level [area under the ROC curve (AUC) =0.802] had greater value than BMI (0.675) for the diagnosis of the pathologic T stage PCa, and that a combination of BMI and PSA (combined AUC =0.822) could improve locally advanced PCa diagnosis. Conclusions: BMI and PSA are independent risk factors for locally advanced PCa. They may play a key part in locally advanced PCa.

20-HETE mediated TRPV1 activation drives allokinesis via MrgprA3+ neurons in chronic dermatitis.

Rationale: Noxious stimuli are often perceived as itchy in patients with chronic dermatitis (CD); however, itch and pain mechanisms of CD are not known. Methods: TRPV1 involvement in CD was analyzed using a SADBE induced CD-like mouse model, and several loss- and gain-of-function mouse models. Trigeminal TRPV1 channel and MrgprA3+ neuron functions were analyzed by calcium imaging and whole-cell patch-clamp recordings. Lesional CD-like skin from mice were analyzed by unbiased metabolomic analysis. 20-HETE availability in human and mouse skin were determined by LC/MS and ELISA. And finally, HET0016, a selective 20-HETE synthase inhibitor, was used to evaluate if blocking skin TRPV1 activation alleviates CD-associated chronic itch or pain. Results: While normally a pain inducing chemical, capsaicin induced both itch and pain in mice with CD condition. DREADD silencing of MrgprA3+ primary sensory neurons in these mice selectively decreased capsaicin induced scratching, but not pain-related wiping behavior. In the mice with CD condition, MrgprA3+ neurons showed elevated ERK phosphorylation. Further experiments showed that MrgprA3+ neurons from MrgprA3;Braf mice, which have constitutively active BRAF in MrgprA3+ neurons, were significantly more excitable and responded more strongly to capsaicin. Importantly, capsaicin induced both itch and pain in MrgprA3;Braf mice in an MrgprA3+ neuron dependent manner. Finally, the arachidonic acid metabolite 20-HETE, which can activate TRPV1, was significantly elevated in the lesional skin of mice and patients with CD. Treatment with the selective 20-HETE synthase inhibitor HET0016 alleviated itch in mice with CD condition. Conclusion: Our results demonstrate that 20-HETE activates TRPV1 channels on sensitized MrgprA3+ neurons, and induces allokinesis in lesional CD skin. Blockade of 20-HETE synthesis or silencing of TRPV1-MrgprA3+ neuron signaling offers promising therapeutic strategies for alleviating CD-associated chronic itch.

Creating a novel multiparametric magnetic resonance imaging-based biopsy strategy for reducing unnecessary prostate biopsies: a retrospective cohort study.

Background: The overdiagnosis of prostate cancer (PCa) caused by unnecessary prostate biopsy has become a worldwide problem that urgently requires a solution. We aimed to reduce the unnecessary prostate biopsies and increase the detection rate of clinically significant PCa (csPCa) by creating a novel multiparametric magnetic resonance imaging (mpMRI)-based strategy. Methods: A total of 1,194 eligible patients who underwent transperineal prostate biopsies from January 2018 to December 2022 were included in this retrospective study. Of these patients, 1,080 who received prostate biopsies from January 2018 to July 2022 were regarded as cohort 1 for primary analysis, and 114 patients who received prostate biopsies from August 2022 to December 2022 were collected in cohort 2 for validation. All the mpMRI images were quantitatively evaluated by the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v. 2.1). The diagnostic performances were assessed through the receiver operating characteristic (ROC) curve and area under the curve (AUC) and were compared with the DeLong test. Cancer diagnosis-free survival analysis was performed using the Kaplan-Meier method and log-rank test. The primary endpoint of this study was clinically significant PCa with an International Society of Urological Pathology (ISUP) grade ≥2. Results: In cohort 1, the results of ROC curves demonstrated that the PI-RADS score had a higher diagnostic accuracy (AUC =0.898 for any-grade PCa; AUC =0.917 for csPCa) than did the other clinical variables (P<0.001). Under the novel mpMRI-based biopsy strategy, all patients with PI-RADS 1 can safely avoid prostate biopsy. For patients with PI-RADS 2, prostate biopsy should be considered for patients with prostate-specific antigen density (PSAD) ≥0.3 ng/mL2 and prostate volume <65 mL. As for patients with PI-RADS 3, structured surveillance programs can be a viable option if PSAD <0.3 ng/mL2 and prostate volume ≥65 mL. Finally, patients with a PI-RADS score of 4 and 5 should undergo prostate biopsy due to the high probability of clinically significant PCa. In the validation analysis of cohort 2, 48 patients were placed into a biopsy-spared group with no csPCa cases, while 66 patients were placed in a biopsy-needed group, with an csPCa detection rate of 50.0%. Overall, the novel strategy demonstrated a sensitivity, specificity, positive predictive value, and negative predictive value of 98.9%, 57.5%, 50.5%, and 99.2%, respectively, for diagnosing csPCa. Conclusions: An mpMRI-based biopsy strategy can effectively avoid about 40% of prostate biopsies and maintain a high detection rate for clinically significant PCa. It can further provide valuable guidance for patients and physicians in considering the necessity of prostate biopsy.

Stent fracture after transjugular intrahepatic portosystemic shunt placement using the bare metal stent/stent-graft combination technique.

BACKGROUND: A transjugular intrahepatic portosystemic shunt (TIPS) is widely placed to treat portal hypertension. Because the Viatorr® stent (W. L. Gore and Associates, Flagstaff, AZ, United States) is not available in all hospitals in China, the bare metal stent (BMS)/stent-graft combination technique is still popular for TIPS construction. Stent fracture is a complication after TIPS placement using this technique, with limited available literature focusing on it. AIM: To assess the incidence of stent fracture after TIPS placement using the BMS/ stent-graft combination technique and to identify the risk factors for stent fracture. We proposed technique modifications to improve the clinical results of TIPS placement with the BMS/stent-graft combination technique. METHODS: We retrospectively analyzed the computed tomography (CT) data of all patients with portal hypertension who underwent the TIPS procedure between June 2011 and December 2021 in a single center. Patients implanted with the BMS/stent graft and had follow-up imaging data available were included. We identified patients with stent fracture and analyzed their characteristics. Multivariable logistic regression was applied to identify the potential predictors of stent fracture. RESULTS: Of the 68 included patients, stent fracture occurred in seven (10.3%) patients. Based on CT images, the stent fractures were categorized into three types. Our study consisted of four (57.1%) type I fractures, one (14.3%) type II fracture, one (14.3%) type IIIa fracture, and one (14.3%) type IIIb fracture. After adjusting for covariates, multivariable logistic regression revealed that the risk factors for stent fracture were the implantation of a greater number of stents [adjusted odds ratio (aOR) = 22.2, 95% confidence interval (CI): 1.2-415.4, P = 0.038] and a larger proximal sagittal stent bending angle (aOR = 1.1, 95%CI: 1.0-1.3, P = 0.020). CONCLUSION: Stent fracture occurred in approximately 10% of patients with portal hypertension who underwent TIPS with the BMS/stent-graft combination technique. The number of implanted stents and stent bending angle at the inferior vena cava end were predictors of stent fracture, which suggests that the incidence of stent fracture could potentially be reduced by procedural modifications.

Protocol for SNOTOB study: radical prostatectomy without prostate biopsy following 18F-PSMA-1007 PET/CT based on a diagnostic model: a single-centre, single-arm, open-label study.

INTRODUCTION: Nowadays, invasive prostate biopsy is the standard diagnostic test for patients with suspected prostate cancer (PCa). However, it has some shortcomings such as perioperative complications, economic and psychological burden on patients, and some patients may undergo repeated prostate biopsy. In this study protocol, our aim is to provide a non-invasive diagnostic strategy we call the 'prostate-specific membrane antigen (PSMA) combined model' for the diagnosis of PCa. If patients are diagnosed with PCa using PSMA combined model, we want to prove these patients can receive radical prostatectomy directly without prior prostate biopsies. METHODS: The SNOTOB trial adopts a prospective, single-centre, single-arm, open-label study design. The PSMA combined model consists of a diagnostic model based on what we previously reported and 18F-PSMA-1007 positron emission tomography/CT (18F-PSMA-1007 PET/CT) examinations in series. First, patients use the diagnostic model (online address: https://ustcprostatecancerprediction.shinyapps.io/dynnomapp/) to calculate the risk probability of clinically significant PCa (csPCa). When the risk probability of csPCa is equal or greater than 0.60, 18F-PSMA-1007 PET/CT will be applied for further diagnosis. If patients are still considered as csPCa after 18F-PSMA-1007 PET/CT examinations, we define this condition as positive results of PSMA combined model. Subsequently, we will recommend these patients to accept radical prostatectomy without prostate biopsy directly. Finally, the diagnostic performance of PSMA combined model will be verified with the pathological results. Totally, 57 patients need to be enrolled in this clinical trial. ETHICS AND DISSEMINATION: This study was approved by the ethics committee of The First Affiliated Hospital of USTC (No. 2022KY-142). The results of this study will be published in peer-reviewed journals and reported at academic conferences. TRIAL REGISTRATION NUMBER: NCT05587192.

Developing a diagnostic model for predicting prostate cancer: a retrospective study based on Chinese multicenter clinical data.

ABSTRACT: The overdiagnosis of prostate cancer (PCa) caused by nonspecific elevation serum prostate-specific antigen (PSA) and the overtreatment of indolent PCa have become a global problem that needs to be solved urgently. We aimed to construct a prediction model and provide a risk stratification system to reduce unnecessary biopsies. In this retrospective study, clinical data of 1807 patients from three Chinese hospitals were used. The final model was built using stepwise logistic regression analysis. The apparent performance of the model was assessed by receiver operating characteristic curves, calibration plots, and decision curve analysis. Finally, a risk stratification system of clinically significant prostate cancer (csPCa) was created, and diagnosis-free survival analyses were performed. Following multivariable screening and evaluation of the diagnostic performances, a final diagnostic model comprised of the PSA density and Prostate Imaging-Reporting and Data System (PI-RADS) score was established. Model validation in the development cohort and two external cohorts showed excellent discrimination and calibration. Finally, we created a risk stratification system using risk thresholds of 0.05 and 0.60 as the cut-off values. The follow-up results indicated that the diagnosis-free survival rate for csPCa at 12 months and 24 months postoperatively was 99.7% and 99.4%, respectively, for patients with a risk threshold below 0.05 after the initial negative prostate biopsy, which was significantly better than patients with higher risk. Our diagnostic model and risk stratification system can achieve a personalized risk calculation of csPCa. It provides a standardized tool for Chinese patients and physicians when considering the necessity of prostate biopsy.

Diagnostic value and immune infiltration characterization of YTHDF2 as a critical m6A regulator in osteoarthritic synovitis.

BACKGROUND: N6-methyladenosine (m6A) is a universal RNA modification pattern regulated by multiple m6A regulators. In osteoarthritis (OA), m6A regulators influence disease progression by regulating cartilage degradation. However, the function of m6A regulators in synovial tissue remains unclear. In this work, we investigated the biological significance of m6A regulators in osteoarthritic synovitis. METHODS: Datasets were acquired from Gene Expression Omnibus. Differential analysis of merged data identified the differentially expressed m6A regulators. Machine learning models were used to evaluate genetic importance. To predict disease risk, a nomogram was constructed based on above m6A regulators. Cluster analysis divided the OA sample into different subgroups. Immune infiltration revealed the immune m6A regulators, which were validated using clinical samples. Eventually, a competing endogenous RNA (ceRNA) network was constructed. RESULTS: We acquired five differentially expressed m6A regulators and a random forest model. The nomogram accurately predicted disease risk. We identified 122 differentially expressed genes between two m6A subgroups. The analysis of immune infiltration showed that YTHDF2 was an immune-related m6A regulator closely related with macrophages. In clinical samples, the protein and mRNA contents of YTHDF2 were consistent with the results of bioinformatic analysis. The ceRNA network based on YTHDF2 revealed 75 lncRNA nodes and 19 miRNA nodes. CONCLUSION: YTHDF2 has a high diagnostic value in the synovitis of OA and significantly influences the immune status of patients. Hence, YTHDF2, a critical m6A regulator, may provide a biomarker for diagnosis and immune therapy of osteoarthritic synovitis.

Establishment and validation of a prognostic nomogram for patients with renal cell carcinoma based on SEER and TCGA database.

Background: Renal cell carcinoma (RCC) is a lethal urological malignancy. Precise risk-stratification is very important for decision-making in postoperative patient management. This study aimed to establish and validate a prognostic nomogram of overall survival (OS) in patients with RCC based on Surveillance, Epidemiology, and End Results (SEER) and TCGA database. Methods: The retrospective data of 40,154 patients diagnosed with RCC during 2010 to 2015 from SEER database (development cohort) and 1,188 patients from TCGA database (validation cohort) were downloaded for analysis. Independent prognostic factors were identified by univariate and multivariate Cox regression analyses and adopted to set up a predictive nomogram of OS. The discrimination and calibration of the nomogram were evaluated by ROC curves, C-index values, and calibration plots, and survival analyses were conducted using Kaplan-Meier curves and long-rank tests. Results: The results of multivariate Cox regression analysis demonstrated that age, sex, tumor grade, the American Joint Committee on Cancer (AJCC) stage, tumor size, and pathological types were independent predictors of the OS of RCC patients. These variables were integrated to construct the nomogram, and verification was conducted subsequently. The area under the ROC curve values of 3- and 5-year survival were 0.785 and 0.769 in the development cohort and 0.786 and 0.763 in the validation cohort. The C-index was 0.746 (95% CI: 0.740-0.752) in the development cohort and 0.763 (95% CI: 0.738-0.788) in the validation cohort, indicating good performance of the nomogram. Calibration curve analysis also suggested supreme accuracy on prediction. Finally, patients in the development and validation cohorts were stratified into three risk-level groups (high, intermediate, and low) based on the risk scores calculated by the nomogram, and significant differences in OS were observed among these three groups. Conclusions: In this study, a prognostic nomogram was established to provide tool for clinicians to better advise RCC patients, determine the follow-up strategies and to select suitable patients for clinical trials.

Analysis of Madelung disease based on sc-RNA sequencing: A case report and literature review.

Madelung disease (MD) was first described by Brodie in 1846 as a rare multiple lipoma. It is a benign tumor characterized by symmetrical diffuse adipose tissue deposition in the proximal extremities and neck. Until now, the etiology and pathogenesis of the disease have not been fully explained, resulting in difficulties in diagnosis and treatment; moreover, palliative treatment, such as surgical resection of adipose tissue or liposuction, is still the mainstream treatment for MD. However, the effectiveness of palliative surgery is limited, and most patients still relapse or metastasize after treatment. Therefore, we analyzed the relationship between tumor cells and immune cells in MD using single-cell RNA sequencing for the first time and combined an analysis of our results with a review of previous literature reports. Our study provides a new perspective on the pathogenesis of MD and provides a vital clinical basis for targeted therapy. DATA AVAILABILITY: The authors declare that all the data supporting the findings of this study are available within the article and its Supplemental information files.

Perineal nerve block versus periprostatic block for patients undergoing transperineal prostate biopsy (APROPOS): a prospective, multicentre, randomised controlled study.

Background: We aimed to investigate perineal nerve block versus periprostatic block in pain control for men undergoing a transperineal prostate biopsy. Methods: In this prospective, randomised, blinded and parallel-group trial, men in six Chinese hospitals with suspected prostate cancer were randomly assigned (1:1) at the point of local anaesthesia to receive a perineal nerve block or periprostatic block and followed by a transperineal prostate biopsy. Centres used their usual biopsy procedure. Operators who performed anaesthesia were trained in both techniques before the trial and were masked to the randomised allocation until the time of anaesthesia and were not involved in the subsequent biopsy procedure and any assessment or analysis. Other investigators and the patients were masked until trial completion. The primary outcome was the level of the worst pain experienced during the prostate biopsy procedure. Secondary outcomes included pain (post-biopsy at 1, 6 and 24 h), changes in blood pressure, heart rate and breathing rate during the biopsy procedure, external manifestations of pain during biopsy, anaesthesia satisfaction, the detection rate of PCa and clinically significant PCa. This trial is registered on ClinicalTrials.gov, NCT04501055. Findings: Between August 13, 2020, and July 20, 2022, 192 men were randomly assigned to perineal nerve block or periprostatic block, 96 per study group. Perineal nerve block was superior for the relief of pain during the biopsy procedure (mean 2.80 for perineal nerve block and 3.98 for periprostatic block; adjusted difference in means -1.17, P < 0.001). Although the perineal nerve block had a lower mean pain score at 1 h post-biopsy compared with the periprostatic block (0.23 vs 0.43, P = 0.042), they were equivalent at 6 h (0.16 vs 0.25, P = 0.389) and 24 h (0.10 vs 0.26, P = 0.184) respectively. For the change in vital signs during biopsy procedure, perineal nerve block was significantly superior to periprostatic block in terms of maximum value of systolic blood pressure, maximum value of mean arterial pressure and maximum value of heart rate. There are no statistical differences in average value of systolic blood pressure, average value of mean, average value of heart rate, diastolic blood pressure and breathing rate. Perineal nerve block was also superior to periprostatic block in external manifestations of pain (1.88 vs 3.00, P < 0.001) and anaesthesia satisfaction (8.93 vs 11.90, P < 0.001). Equivalence was shown for the detection rate of PCa (31.25% for perineal nerve block and 29.17% for periprostatic block, P = 0.753) or csPCa (23.96% for perineal nerve block and 20.83% for periprostatic block, P = 0.604). 33 (34.8%) of 96 patients in the perineal nerve block group and 40 (41.67%) of 96 patients in the periprostatic block group had at least one complication. Interpretation: Perineal nerve block was superior to periprostatic block in pain control for men undergoing a transperineal prostate biopsy. Funding: Grant 2019YFC0119100 from the National Key Research and Development Program of China.

An in vitro investigation of the apoptosis-inducing activity of corosolic acid in breast cancer cells.

Objectives: Breast cancer is the most prevalent cancer among females with different molecular subtypes. Corosolic acid is a pentacyclic triterpenoid with anti-cancer properties. Materials and Methods: The MTT assay was used to assess the cytotoxic activity of corosolic acid on MDA-MB-231 and MCF7 cell lines. To determine the apoptotic cells, the flow cytometry technique was utilized. The expression levels of apoptosis-related genes and proteins were quantified using quantitative real time-PCR (qRT-PCR) and Western blotting methods. The activity of caspase enzymes was measured by spectrophotometry. Results: Corosolic acid significantly inhibited the proliferation of both cell lines compared with controls. This agent markedly induced apoptosis in MDA-MB-231 cells but did not affect MCF7 cells compared with controls. Treating the MADA-MB-231 and MCF7 cell lines with corosolic acid showed an inducing effect on apoptosis-associated caspases, including Caspase-8, 9, and -3, in MADA-MB-231 cells with no effect on apoptotic markers in MCF7 cells. Further experiments uncovered corosolic acid-induced apoptosis in MADA-MB-231 cells by decreasing the expression of the phosphorylated form of JAK2 and STAT3 proteins. Conclusion: The present data suggested that corosolic acid is an apoptosis-inducing phytochemical in triple-negative breast cancer MADA-MB-231 cells. Also, corosolic acid triggered apoptosis in these cells by stimulating both pathways of apoptosis and inhibiting the JAK/STAT signaling. Furthermore, corosolic acid was found to inhibit MCF7 cell proliferation by a non-apoptotic mechanism.

Aconitine - A promising candidate for treating cold and mechanical allodynia in cancer induced bone pain.

BACKGROUND AND AIMS: Patients suffering from cancer induced bone pain (CIBP) have a poor quality of life that is exacerbated by the lack of effective therapeutic drugs. Monkshood is a flowering plant that has been used in traditional Chinese medicine where it has been used to relieve cold pain. Aconitine is the active component of monkshood, but the molecular mechanism for how this compound reduces pain is unclear. METHODS AND RESULTS: In this study, we employed molecular and behavioral experiments to explore the analgesic effect of aconitine. We observed aconitine alleviated cold hyperalgesia and AITC (allyl-isothiocyanate, TRPA1 agonist) induced pain. Interestingly, we found aconitine directly inhibits TRPA1 activity in calcium imaging studies. More importantly, we found aconitine alleviated cold and mechanical allodynia in CIBP mice. Both the activity and expression of TRPA1 in L4 and L5 DRG (Dorsal Root Ganglion) neurons were reduced with the treatment of aconitine in the CIBP model. Moreover, we observed aconiti radix (AR) and aconiti kusnezoffii radix (AKR), both components of monkshood that contain aconitine, alleviated cold hyperalgesia and AITC induced pain. Furthermore, both AR and AKR alleviated CIBP induced cold allodynia and mechanical allodynia. CONCLUSIONS: Taken together, aconitine alleviates both cold and mechanical allodynia in cancer induced bone pain via the regulation of TRPA1. This research on the analgesic effect of aconitine in cancer induced bone pain highlights a component of a traditional Chinese medicine may have clinical applications for pain.

Osthole relieves skin damage and inhibits chronic itch through modulation of Akt/ZO-3 pathway in atopic dermatitis.

Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin condition and significantly reduces quality of life. Tight junction (TJ), which is located directly beneath the stratum corneum, maintains skin barrier function and aids in the identification of the cell's "territory". We evaluated seventeen TJ related genes to explore AD related alterations of TJ. Remarkably, we found that the expression of ZO-3, a gene that had not been linked to the development of TJ in AD, was significantly down-regulated in the skin of AD mice and patients. siRNA mediated knock-down of ZO-3 significantly decreased transepithelial electrical resistance in HaCaT cells, demonstrating that ZO-3 is essential to epidermal barrier function. In addition to ZO-3 downregulation, protein kinase B (Akt) phosphorylation was increased in the skin of AD mice. We further confirmed an inverse relationship between Akt phosphorylation and ZO-3 expression in AD using HaCaT cells and mouse model. Finally, we tested the efficacy of osthole as a treatment for AD in mice and HaCaT cells. Osthole inhibits Akt phosphorylation, and thereby enhances ZO-3 expression in mouse models of AD, resulting in greatly lessened AD associated skin damage and chronic itch, and osthole also increased the expression of ZO-3 in HaCaT cells by inhibiting the phosphorylation of Akt. Together, we established that ZO-3 is essential for the development of TJ in AD skin and HaCaT cells, and our findings provide fresh support for osthole's ability to protect ZO-3 expression and the epidermal barrier in AD.

Gap-directed chemical lift-off lithographic nanoarchitectonics for arbitrary sub-micrometer patterning.

We introduce a unique soft lithographic operation that exploits stamp roof collapse-induced gaps to selectively remove an alkanethiol self-assembled monolayer (SAM) on Au to generate surface patterns that are orders of magnitude smaller than structures on the original elastomer stamp. The smallest achieved feature dimension is 5 nm using a micrometer-scale structured stamp in a chemical lift-off lithography (CLL) process. Molecular patterns retained in the gaps between stamp features and their circumscribed or inscribed circles follow mathematical predictions, and their sizes can be tuned by altering the stamp structure dimensions, including height, pitch, and shape. These generated surface molecular patterns can function as biorecognition arrays or be transferred to the underneath Au layer for metallic structure creation. By combining CLL process with this gap phenomenon, soft material properties that are previously thought as demerits can be used to achieve sub-10 nm features in a straightforward sketch.

The role of the orbitofrontal cortex and insula for prognosis of mesial temporal lobe epilepsy.

OBJECTIVE: We investigated the network between the medial temporal lobe (MTL) and extratemporal structures in patients with mesial temporal lobe epilepsy (MTLE) in order to explain the recurrence of MTLE after surgery. This study contributes to our current understanding of MTLE with stereotactic electroencephalography (SEEG). METHODS: We conducted a retrospective study of SEEG in 20 patients with MTLE in order to observe and analyze the intensity of interictal high-frequency oscillations (HFOs), as well as the dynamic course of coherence connectivity values of the MTL and extratemporal structures during the initial phase of the seizure. The results correlated with the patient prognosis. RESULTS: First, the presence of HFOs was observed during the interictal period in all 20 patients; these were localized to the MTL in 17 patients and the orbitofrontal cortex in seven patients and the insula in six patients. The better the prognosis, the greater the localization of the HFOs concentration in the MTL structures (p < 0.05). Second, significantly enhanced connectivity of MTL structures with the orbitofrontal cortex and insula was observed in most patients with MTLE, before and after the seizure onset (p < 0.05). Finally, the connectivity between extratemporal structures, such as the orbitofrontal cortex and insula, and MTL structures was significantly stronger in patients who had a worse prognosis than in other patients, before and after seizure onset (p < 0.05). INTERPRETATION: The epileptogenic network in recurrent MTLE is not limited to MTL structures but is also associated with the orbitofrontal cortex and insula. This can be used as a potential indicator for predicting the prognosis of patients after surgery, providing an important avenue for future clinical evaluation.