Clinicopathological Correlation and Recurrence Outcome of Adnexal Involvement on Primary Extramammary Paget's Disease (EMPD).

Introduction Primary extramammary Paget's disease (EMPD) is a rare neoplasm that manifests as well-defined erythematous plaques, often misdiagnosed due to its similarity with different dermatoses. It may exhibit invasive features, involving adnexal invasions. The study aims to assess and compare the clinicopathological correlation of primary EMPD with adnexal features. Materials and methodology The monocentric observational retrospective study observed 43 confirmed primary EMPD cases in patients aged 45-95, excluding those with infectious dermatoses, pseudo-tumors, secondary lesions, or survived less than a month. Demographical, clinical and pathological observations were recorded. Expert dermatopathologists, blinded to the initial diagnosis, conducted a comprehensive histopathological evaluation yielding differential pathological diagnosis. Statistical analysis involved Pearson's Chi-square, Mann-Whitney U, and Spearman's Correlations for clinicopathological concordance and adnexal features. Recurrence was evaluated using Kaplan-Meier and log-rank tests, while multivariate recurrence analyses include Cox regression. A p-value < 0.05 was deemed significant. Results There was a significant association between adnexal involvement and the site of lesion (p < 0.05). There was a significant association (p < 0.05) between involved adnexal depth and primary EMPD subtypes. Adnexal involvement has a significant association with the concordance rates derived from clinicopathological correlations (p < 0.05). Smaller lesions and non-invasive EMPD significantly predict longer recurrence onset (p < 0.01). The primary EMPD subtype was the only independent predictor for recurrence time using the Cox regression model. Conclusion Adnexal proliferation in primary EMPD is considered vital on clinicopathological correlations and recurrence predictions, suggestive of its utility on both diagnosis and prognosis.

Mimicry unveiled: The challenging diagnosis of pigmented purpura-like mycosis fungoides initially misdiagnosed as pigmented purpura.

Key Clinical Message: Unlike most cases, the lesions were localized to the dorsum of the hand, lacked pruritus (itching), and did not exhibit "sperm-like blood vessels," which are typically pathognomonic to classical MF. Abstract: The study presents a rare case involving a 44-year-old woman who developed a skin condition on the base of her left thumb. Initially misdiagnosed as pigmented purpura, the need for further investigation arose to determine the nature of the condition accurately. The medical evaluation encompassed a comprehensive analysis of the patient's skin ailment. A series of diagnostic examinations were conducted to ascertain the underlying cause. Although routine blood tests yielded unremarkable results, the distinct characteristics of the rash prompted a more thorough investigation. Subsequent assessment revealed that the skin condition was not pigmented purpura, as initially presumed, but rather a manifestation of cutaneous T-cell lymphoma (CTCL) known as mycosis fungoides (MF). MF is an infrequent lymphoma predominantly affecting individuals aged 45-65, exhibiting a male-to-female sex ratio of 2:1. The annual incidence of MF ranges from 0.3 to 0.96 cases per 100,000 individuals. The woman's skin exhibited discrete patches adorned with colored dots, progressively thickening and pigmentation. Notably, the absence of pruritus did not dispel suspicion. This case underscores the significance of accurately diagnosing uncommon dermatological disorders to facilitate appropriate medical intervention. The unique appearance of the rash and its distinctive features, despite normal blood results, enabled the identification of MF. The patient's treatment encompassed a combination of steroids and narrowband UV therapy. Vigilance, continued research, and heightened awareness are paramount for early intervention and improved patient outcomes. Such efforts contribute to an enhanced understanding of the complexities of this condition.

Eruptive Pruritic Papular Porokeratosis (EPPP) Presenting as a Rare Facial Manifestation Associated With COVID-19: A Case Report.

This case report presents a rare instance of Eruptive Pruritic Papular Porokeratosis (EPPP) in a 71-year-old Chinese male, emerging on atypical sites (face, scalp, and ears) following a COVID-19 infection, and explores the potential link between viral infections and EPPP onset. The patient's lesions, characterized by annular brown patches with hyperkeratotic ridges, showed significant improvement following treatment with Baricitinib and Acitretin. This case underscores the need for awareness of unusual presentations of EPPP and suggests the potential efficacy of Janus Kinase (JAK) inhibitors in treatment, prompting further research into the pathophysiological connections between EPPP and viral infections. Adherence to the SCARE 2023 guidelines ensures a comprehensive and transparent case presentation.

Lessons from an elderly patient with pulmonary embolism caused by protein S deficiency: a case report.

BACKGROUND: Lower limb deep vein thrombosis (DVT) concurrent with pulmonary embolism (PE) is perilous, particularly in the elderly, exhibiting heterogeneity with thrombophilia mutations. Tailored treatment is essential, yet sudden deaths complicate causative factor elucidation. This report emphasizes genetic testing necessity in PE patients with thrombophilia indicators, facilitating cause identification, personalized treatment guidance, and family education. CASE PRESENTATION: This study details a 75-year-old Chinese woman with DVT and PE, where genetic testing identified thrombophilia, guiding personalized treatment decisions. RESULTS: Upon admission, the patient, after over 10 days of bed rest, presented chest tightness, shortness of breath, and unilateral leg swelling. Diagnostic measures revealed DVT and a substantial PE. Genetic testing identified a PROS1 gene C200A>C mutation, reducing protein S activity. Following 2 weeks of anticoagulation and inferior vena cava filter insertion, the patient, discharged, initiated lifelong anticoagulant therapy. A 1-year follow-up showed no recurrent thrombotic events. Family members carrying the mutation received informed and educational interventions. CONCLUSION: Genetic testing for thrombophilic predisposition post-PE is crucial, elucidating etiology, guiding individualized treatment, and playing a pivotal role in family education.

Lateral Retinacular Release for Treatment of Excessive Lateral Pressure Syndrome: The Capsule-Uncut Immaculate (CUI) Technique.

Lateral retinacular release of the patella is the main surgical treatment for excessive lateral pressure syndrome. It was first described by Merchant and Mercer in 1974. The main complications of arthroscopic lateral retinacular release are hemarthrosis and medial patellar instability. The main causes of these complications are the disturbance of the synovial membrane of the joint capsule and excessive release of the lateral retinaculum. In this article, we introduce a method for arthroscopic lateral retinacular release that maintains the overall structure of the joint capsule: capsule-uncut immaculate (CUI) lateral retinacular release.

A Case Report on Mid-Dermal Elastolysis: A Distinctive Presentation on the Neck.

Mid-dermal elastolysis (MDE) is a very rare and acquired skin condition. MDE has a variety of clinical manifestations that can be presented with a reticular erythematous patch with telangiectasis, perifollicular popular protrusions, or finely wrinkled skin. A biopsy is always necessary to rule out other potential elastic fiber disorders. In this case study, a 33-year-old female with an odd MDE presentation in her neck area is examined. No contributing factors, apart from exposure to sunlight, could be gleaned from the patient's history. The patient didn't benefit from the application of various types of topical agents or any other therapies to lessen the size and advancement of the lesion. In this distinct case, we discuss clinical and histological findings and the treatment plan offered, as well as include a concise review of specific past literature.

Novel heterotopic continental ileal reservoir based on the Mitrofanoff principle: a case report and review of the literature.

For patients undergoing radical cystectomy with standard lymphadenectomy for bladder cancer, appropriate urinary diversion (with a pouch and conduit) improves postoperative quality of life, reduces postoperative complications, and prolongs survival. We developed a novel heterotopic ileal reservoir to achieve these goals. This report describes the methodology involved and the incidence of intraoperative and postoperative complications. Three patients who underwent novel heterotopic ileal reservoir creation following radical cystectomy and standard lymphadenectomy (for bladder cancer) were evaluated. The ileum served as a pouch in which the ureters and appendix were implanted by extramural tunnelling. The appendix served as a conduit and pelvic reperitonealization was performed. Operative times, intraoperative blood loss, time to intestinal function recovery, incidence of intestinal obstruction and ureteric reflux, and bladder volumes and continence levels were evaluated. The surgical intervention was successful with operation times ranging 410-525 min, blood loss ranging 300-700 ml, and recovery time for intestinal function ranging 3-5 days. The postoperative hospitalization time was 11-15 days. Subileus occurred in patient B, who recovered after fasting and fluid replacement. Patients B and C achieved complete continence 6 weeks after surgery, while patient A experienced umbilical urine leakage with catheterization time intervals that exceeded 4 h. At 3 months after surgery, the bladder capacities of all patients ranged 250-370 ml. Follow-up cystography suggested the presence of bilateral ureteral reflux in patient A, with mild and moderate reflux on the left right sides, respectively. All patients achieved complete continence. Patients were followed for 3-9 months postoperatively; chest and abdominal computed tomography and cystography showed absence of hydronephrosis, recurrence, or distant metastasis during this period. The novel heterotopic continent ileal reservoir described in this study may be suitable for selected patients. The surgical procedure is safe when performed by well-trained and highly experienced urologists.

HUVECs affect HuT-78 cell apoptosis and cytokine production via the HIF-1α-PD-L1/PD-1 pathway under hypoxia.

We investigated whether human umbilical vein endothelial cells (HUVECs) under hypoxic conditions can suppress the production of cytokines in Hut-78 cells via the HIF-1α/PD-L1/PD-1 pathway, and the intervention effect of Nivolumab. HUVECs and HuT-78 cells were monocultured or cocultured in a tri-gas incubator with or without Nivolumab pretreatment. Real-time PCR, western blotting, and protein chips were used. Transcriptional regulation of PD-L1 and PD-1 by HIF-1α was analyzed by ChIP-qPCR and luciferase reporter gene assays. Apoptosis was assessed by flow cytometry. In HuT-78 cells, hypoxic monoculture significantly increased the expression of HIF-1α, PD-1, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-α, and Bax, decreased the expression of Bcl-2, and resulted in increased apoptosis. In comparison to hypoxic monoculture, hypoxic coculture significantly reduced the expression of IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, and IFN-α, as well as Bcl-2, in HuT-78 cells. Meanwhile, Bax expression was significantly increased with elevated apoptosis in HuT-78 cells. However, pretreatment with Nivolumab significantly antagonized the reduction in cytokines and the elevation in apoptosis in HuT-78 cells. Chip-qPCR and luciferase reporter gene assays demonstrated that hypoxia significantly increased the binding of HIF-1α to the upstream regulatory regions of PD-1 at -63 and -66 bp and PD-L1 at -571 bp, promoting their transcription. Therefore, HUVECs under hypoxia can reduce cytokine production and inhibit their own apoptosis in co-culture with HuT-78 cells via the HIF-1α/PD-L1/PD-1 pathway. These findings provide new clues for exploring the combined use of immune checkpoint inhibitors and anti-angiogenic drugs in clinical settings.

Automatic localization of target point for subthalamic nucleus-deep brain stimulation via hierarchical attention-UNet based MRI segmentation.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for patients with advanced Parkinson's disease, the outcome of this surgery is highly dependent on the accurate placement of the electrode in the optimal target of STN. PURPOSE: In this study, we aim to develop a target localization pipeline for DBS surgery, considering that the heart of this matter is to achieve the STN and red nucleus segmentation, a deep learning-based automatic segmentation approach is proposed to tackle this issue. METHODS: To address the problems of ambiguous boundaries and variable shape of the segmentation targets, the hierarchical attention mechanism with two different attention strategies is integrated into an encoder-decoder network for mining both semantics and fine-grained details for segmentation. The hierarchical attention mechanism is utilized to suppress irrelevant regions in magnetic resonance (MR) images while build long-range dependency among segmentation targets. Specifically, the attention gate (AG) is integrated into low-level features to suppress irrelevant regions in an input image while highlighting the salient features useful for segmentation. Besides, the self-attention involved in the transformer block is integrated into high-level features to model the global context. Ninety-nine brain magnetic resonance imaging (MRI) studies were collected from 99 patients with Parkinson's disease undergoing STN-DBS surgery, among which 80 samples were randomly selected as the training datasets for deep learning training, and ground truths (segmentation masks) were manually generated by radiologists. RESULTS: We applied five-fold cross-validation on these data to train our model, the mean results on 19 test samples are used to conduct the comparison experiments, the Dice similarity coefficient (DSC), Jaccard (JA), sensitivity (SEN), and HD95 of the segmentation for STN are 88.20%, 80.32%, 90.13%, and 1.14 mm, respectively, outperforming the state-of-the-art STN segmentation method with 2.82%, 4.52%, 2.56%, and 0.02 mm respectively. The source code and trained models of this work have been released in the URL below: https://github.com/liuruiqiang/HAUNet/tree/master. CONCLUSIONS: In this study, we demonstrate the effectiveness of the hierarchical attention mechanism for building global dependency on high-level semantic features and enhancing the fine-grained details on low-level features, the experimental results show that our method has considerable superiority for STN and red nucleus segmentation, which can provide accurate target localization for STN-DBS.

Nootkatone, a Sesquiterpene Ketone From Alpiniae oxyphyllae Fructus, Ameliorates Metabolic-Associated Fatty Liver by Regulating AMPK and MAPK Signaling.

Metabolic-associated fatty liver disease (MAFLD) is becoming more common due to lifestyle changes. A long-term high-fat and high-glucose diet induces glycolipid metabolism disorders in the liver, which results in the development of MAFLD. To date, there is no specific clinically useful therapeutics for this disease. Natural products or synthetic compounds were screened and investigated to find effective agents for treating MAFLD. In this study, nootkatone (Nok), a natural sesquiterpene ketone isolated from Alpiniae oxyphyllae fructus, was explored for its potential to treat MAFLD, and underlying mechanisms were studied. Our results show that Nok dramatically ameliorated the disordered lipid and glucose metabolism in MAFLD mice, decreased fat accumulation in hepatic tissue, and improved liver injury. Inflammation, metabolic disorder, and oxidative stress were ameliorated in liver tissue based on RNA-seq transcriptome comparison between a Nok-treated group and an MAFLD model group. Furthermore, Nok significantly activated AMPK activity and inhibited MAPK activity, especially the p38 and JNK signaling pathways, in vivo based on western blot analysis. The pharmaceutical effects and potential signaling pathways impacted by Nok were also investigated in L02 cells. Nok significantly promoted the consumption of glucose and decreased the deposition of triglycerides in vitro. The p-AMPKα level was notably upregulated by Nok, indicating dramatic AMPK activation. In addition, Nok decreased the levels of p-ERK1/2, p-p38, and p-JNK. Nok also inhibited the activation of MAPK signaling and, thus, alleviated MAFLD development. Our results suggest that Nok may be useful in treating MAFLD. Nok may ameliorate MAFLD by regulating glycolipid metabolism disorders by activating AMPK and inhibiting MAPK activity. Collectively, this study suggests that Nok is an effective compound for the treatment of MAFLD.

Mangiferin Ameliorates HFD-Induced NAFLD through Regulation of the AMPK and NLRP3 Inflammasome Signal Pathways.

Nonalcoholic fatty liver disease (NAFLD) is closely related to glycolipid metabolism and liver inflammation. And there is no effective drug approved for its clinical therapy. In this study, we focused on mangiferin (Man) and explored its effects and mechanisms on NAFLD treatment based on the regulation of glycolipid metabolism and anti-inflammatory in vivo and in vitro. The results exhibited that Man can significantly attenuate liver injury, insulin resistance, and glucose tolerance in high-fat diet- (HFD-) induced NAFLD mice and significantly reduce fat accumulation and inflammation in hepatic tissue of NAFLD mice. The transcriptome level RNA-seq analysis showed that the significantly different expression genes between the Man treatment group and the HFD-induced NAFLD model group were mainly related to regulation of energy, metabolism, and inflammation in liver tissue. Furthermore, western blots, real-time PCR, and immunohistochemistry experiments confirmed that Man significantly activated the AMPK signal pathway and inhibited NLRP3 inflammasome activation and pyroptosis in NAFLD mice. In in vitro cell experiments, we further confirmed that Man can promote glucose consumption and reduce intracellular triglyceride (TG) accumulation induced by free fatty acids in HepG2 cells and further that it can be blocked by AMPK-specific inhibitors. Western blot results showed that Man upregulated p-AMPKα levels and exhibited a significant AMPK activation effect, which was blocked by compound C. At the same time, Man downregulated the expression of NLRP3 inflammasome-related proteins and inhibited the activation of NLRP3 inflammasome, alleviating cell pyroptosis and inflammation effects. These results indicate that Man anti-NAFLD activity is mediated through its regulation of glucolipid metabolism by AMPK activation and its anti-inflammatory effects by NLRP3 inflammasome inhibition. Our study indicates that Man is a promising prodrug for the therapy of NAFLD patients.

Value of anti-hepatitis B virus in serum tested by enzyme linked immunosorbent assay 3 in diagnosis of hepatitis B: A protocol for systemic review and meta analysis.

INTRODUCTION: This protocol is for a meta analysis that aims to systematically review the diagnostic value of anti-hepatitis B virus in serum tested by the enzyme linked immunosorbent assay in patients with hepatitis B. METHODS AND ANALYSIS: The following electronic databases will be searched from inception to Mar 2021: PubMed, Web of Science, ScienceDirect, EMBASE, MEDLINE, Springer, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Chinese Science and Technology Periodical Database, and Wanfang Database. All study about enzyme linked immunosorbent assay reagents have been published at home and abroad to diagnose hepatitis B virus will be included. MetaDisc 1.4 soft will used to calculate pooled effect size in sensitivity, specifi city, likelihood ratio, diagnostic odds ratio and summary receiver operating characteristic curve, and area under the curve as well. ETHICS AND DISSEMINATION: Formal ethical approval is not required, as the data are not individualized. The findings of this systematic review will be disseminated in a peer-reviewed publication and/or presented at relevant conferences. REGISTRATION NUMBER: INPLASY2020100051.

Erol Basar and the scientific revolution in nonlinear brain dynamics: A selective review.

Erol Basar was one of the most significant neuroscientists of the past century. Two main threads of thought guided Basar's scientific labor: i) the study of brain oscillations and ii) its marriage to basic principles of physics. These two threads provided him with the crucial element to introduce nonlinear random theory into brain research. Until the decade of the seventies, the underling paradigm in studying the electrical activity of the brain was dominated by a simplistic linear systems model that entailed absolute separation between a determinist evoked responses to stimuli and a superimposed background electrical activity considered as "noise". Basar questioned this simplistic linear model and its interpretation. Basar underscored the nonlinear dynamics of the brain, demonstrated for the first time the interaction between evoked and background activity, and widened the study of event-related activity from the time domain to the frequency and time-frequency domain, heralding a new understanding of the event-related dynamics. These advances were a consequence of Basar's fascination with the physics and mathematics of dynamical physical systems which he rightly believed to be the key to understanding the brain. Here we carry out a selected review, based on a scientometric analysis of Basar's scientific trajectory in the field of Brain Dynamics as embodied in 278 peer-reviewed papers. We also report the geographical distribution of Basar's collaborators, distribution of his citations, and his interaction with many international groups. This analysis illustrates the importance of his innovative contributions and the impact it had on our field. It underscores that he is one of the initiators of a "scientific revolution" in neurophysiology: from linear systems to random non-linear systems analysis and the new vision of the brain as a dynamical system.

Half-life determination of 88Rb using the 4πß and 4πßγ-coincidence methods.

Samples of 88Rb were produced by the irradiation of U3O8. A series of procedures were applied to extract pure radioactive solution of 88Rb. Experimental data was recorded by a 4πßγ-coincidence measurement system. Two rounds of experiments were performed to obtain four sets of measurement data. The measured half-life of 88Rb obtained from the average of the 4πß and 4πßγ-coincidence methods was 17.78 ± 0.05 min, in good agreement with previously reported values but with a significantly reduced uncertainty.

Involvement of Spike Protein, Furin, and ACE2 in SARS-CoV-2-Related Cardiovascular Complications.

The novel coronavirus disease 2019 (COVID-19) is a global epidemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). SARS-CoV-2 has a similar structure to severe acute respiratory syndrome coronavirus-1(SARS-CoV-1). The S protein on the surface of the virus is cleaved by host proprotein convertases (PCs) to expose the active N-terminal S1 extracellular domain. Its receptors are angiotensin-converting enzyme 2 (ACE2), and the C-terminal S2 membrane anchoring protein is responsible for translocating the virus into the cell. Among patients with COVID-19, there is a higher prevalence of cardiovascular disease, and more than 7% of patients have suffered myocardial damage due to the infection, but the internal mechanism is still poorly understood. There is currently no specific and effective targeted treatment. Reduction of the patient's morbidity and mortality is an urgent problem that needs to be solved clinically. By exploring the theoretical analysis of PCs and ACE2 in COVID-19 cardiovascular susceptibility, some insights on how to prevent and alleviate adverse cardiovascular prognosis have been provided in this study.

Safranal carried by nanostructured lipid vehicles inhibits generalized epilepsy in mice.

Safranal, a main component of Crocus sativus, is suggested to have neuroprotective effects. The aim of this study was to investigate the effect of safranal and nanostructured lipid vehicle (NLV) carried safranal in acute and chronic experimental mice models of epilepsy. In PILO acute seizure model, safranal dose-dependently extended latency to generalized seizure, decreased the highest seizure stages and the number of generalized seizures. Moreover, NLV carried safranal further enhanced the anti-seizure effect, which is comparable to the action of sodium valproate. Meanwhile, NLV carried safranal reduced and delayed the electroencephalogram spectra power after pilocarpine injection. In histological aspect, safranal dose-dependently reduced the loss of neurons induced by seizure and NLV system further improved this protection at the same dose. In MES acute model, safranal markedly increased the electroconvulsive threshold, where NLV further improved its effect. In PTZ chronic seizure model, NLV carried safranal significantly delayed the kindling rate of progress and the time it took to reach generalized seizures as compared to NLV control group. In conclusion, this study indicates that safranal inhibits generalized seizure in acute and chronic epilepsy models in mice and NLV can enhance this effect. So, NLV carried safranal may have potential value in treatment of generalized epilepsy.

lncRNA ENSMUST00000134285 Increases MAPK11 Activity, Regulating Aging-Related Myocardial Apoptosis.

Previous studies have demonstrated that aging promotes myocardial apoptosis after ischemia/reperfusion, via unknown specific mechanisms. The present study investigates the potential relationship between lncRNAs and aging-related apoptosis by lncRNA/mRNA microarray technology. The results indicate aging increased myocardial lncRNA ENSMUST00000134285 and mMAPK11, confirmed by both bioinformatics analysis and polymerase chain reaction (PCR). Mouse cardiomyocytes were subjected to gene manipulation (ENSMUST00000134285 knockdown and overexpression). Knockdown of ENSMUST00000134285 inhibited MAPK11 activity and increased the myocardial apoptotic ratio (determined by TUNEL staining and caspase activity assays) after hypoxia/reoxygenation. Conversely, overexpression of ENSMUST00000134285 increased MAPK11 activity and decreased the myocardial apoptotic ratio. Furthermore, luciferase reporter assay revealed that miR760 may be a mediator between ENSMUST00000134285 and mMAPK11. We have provided evidence that lncRNAs are the important regulatory molecules in aging-mediated effects upon apoptosis. The apoptosis regulatory effects of aging are complex. Except apoptosis-promoting effects, aging could also inhibit myocardial apoptosis after hypoxia or ischemia. Further studies investigating the mechanisms that aging inhibit myocardial apoptosis after hypoxia/ischemia.

[Application of team approach and key techniques of cleft lip and palate].

The development of an expert consensus based on specific domestic situations will provide practical guidance to the efforts aiming at improving cleft care in China. The team approach of twenty-one cleft centers were pooled together, covering pre-surgical orthopedics, primary surgical repair, orthodontic treatment, alveolar bone graft, secondary deformity correction, palatal fistulae repair, the diagnosis and treatment of velopharyngeal incompetence, speech therapy, otitis media management, and skeletal deformity correction. Agreement was achieved among the authors concerning the application of critical surgical and non-surgical techniques. The ambition of this consensus is to introduce more clinicians to the revolution of sequential treatment of clefts, and form the basis for a more comprehensive cleft care manual in the future.

Hydrostatic pressure and muscarinic receptors are involved in the release of inflammatory cytokines in human bladder smooth muscle cells.

AIMS: Abnormal intravesical pressure results in a series of pathological changes. We investigated the effects of hydrostatic pressure and muscarinic receptors on the release of inflammatory cytokines in rat and human bladder smooth muscle cells (HBSMCs). METHODS: Animal model of bladder outlet obstruction was induced by urethra ligation. HBSMCs were subjected to elevated hydrostatic pressure and/or acetylcholine (Ach). Macrophage infiltration in the bladder wall was determined by immunohistochemical staining. The expression of inflammatory genes was measured by RT-PCR, ELISA and immunofluorescence. RESULTS: In obstructed bladder, inflammatory genes and macrophage infiltration were remarkably induced. When HBSMCs were subjected to 200-300 cm H2 O pressure for 2-24 h in vitro, the expressions of IL-6 and RANTES were significantly increased. Hydrostatic pressure promoted the protein levels of phospho-NFκB p65 and phospho-ERK1/2 as well as muscarinic receptors. Moreover, NFκB or ERK1/2 inhibitors suppressed pressure-induced inflammatory genes mRNA. When cells were treated with 1 µM acetylcholine for 6 h, a significant increase in IL-6 mRNA expression was detected. Acetylcholine also enhanced pressure-induced phospho-NFκB p65 and IL-6 protein expression. Additionally, pressure-induced IL-6 was partially suppressed by muscarinic receptors antagonists. CONCLUSIONS: Hydrostatic pressure and muscarinic receptors were involved in the secretion of inflammatory cytokines in HBSMCs, indicating a pro-inflammatory effect of the two factors in the pathological process of BOO.