Background: Bladder outlet obstruction (BOO), initiated by abnormal mechanical stress, leads to progressive bladder fibrosis and functional decompensation. Abnormal mechanical stress plays a key role in the pathogenesis of various diseases, including fibrosis. However, the mechanisms through which BOO-induced abnormal mechanical stress drives bladder fibrosis remain poorly understood. Recent studies have highlighted that Yes-associated protein 1 (YAP1) serves as a critical integrator of mechanical signals and metabolic alterations. Abnormal mechanical stress can promote disease progression by regulating metabolic enzymes such as glutaminase 1 (GLS1) through YAP1. Alterations in cellular behavior and disease progression induced by abnormal mechanical stress are closely linked to metabolic reprogramming. Targeting this metabolic reprogramming may effectively counteract the resulting cellular alterations and disease progression. Methods: KEGG pathway enrichment was performed using RNA-seq data from a rat BOO model, and YAP1 expression was examined in human and rat bladder tissues. Fibroblasts were cultured under high hydrostatic pressure (HHP) to mimic BOO-induced stress, and YAP1 nuclear translocation and GLS1 expression were assessed by immunofluorescence and western blotting. Fibroblast proliferation, migration, and activation were measured via functional assays and fibrotic protein expression. To clarify the roles of Piezo1 and YAP1, we performed siRNA, inhibitor, and rescue experiments and evaluated their effects on GLS1, glutamine metabolism, and fibroblast activation. In vivo, bladder function and histology were assessed following GLS1 inhibition in BOO rats. Results: YAP1 expression was significantly increased in human and rat bladders with BOO. HHP enhanced nuclear translocation of YAP1 and upregulated GLS1. HHP stimulation also promoted fibroblast proliferation, migration, and activation. Under HHP, Piezo1 acted as the upstream mechanotransducer that activated YAP1, which in turn induced GLS1 expression. Inhibition of Piezo1 or YAP1 reduced GLS1 expression, and blockade of this axis suppressed fibroblast activation in vitro. HHP-induced fibroblast activation relied on GLS1-driven glutamine metabolic reprogramming, and pharmacological blockade of GLS1 effectively attenuated fibrosis and improved bladder function in BOO rats. Conclusions: This study identifies a Piezo1/YAP1/GLS1 axis linking mechanical stress to metabolic reprogramming and fibroblast activation in BOO, which may serve as a therapeutic target to prevent fibrosis and preserve bladder function.

Purpose: Benign prostatic hyperplasia (BPH) is common in elderly men, causing lower urinary tract symptoms (LUTSs). The 1470 nm diode laser, with high vaporization efficiency and good hemostasis, is increasingly used for BPH. This study sought to comprehensively evaluate the efficacy and safety of 1470 nm diode laser enucleation of the prostate (DiLEP) forBPH in a prospective, multicenter study. Methods: Conducted at two hospitals, BPH patients were randomized into two groups. Group A used a new 1470 nm diode laser device (Hefei Han’s Kereida), and Group B utilized a conventional and widely validated 1470 nm laser system (Wuhan Qizhi). Prostate volume (PV), maximum flow rate (Qmax), post-void residual (PVR), International Prostate Symptom Score (IPSS), and Quality of Life (QoL) score were measured pre- and post-operatively. Perioperative indices and complications were also recorded. Results: 143 patients (73 in Group A, 70 in Group B) completed follow-up. Baseline characteristics of two groups were comparable. Vital parameters remained within normal ranges following the surgical procedure. Both groups showed significant improvements in IPSS, QoL, Qmax, and PVR post-operatively, with no significant differences between groups. Complications occurred in 17 patients in Group A and 10 in Group B, all of which resolved spontaneously or were effectively managed with appropriate interventions. Conclusion: 1470 nm DiLEP is an effective and safe BPH treatment, relieving symptoms with few complications. The new device from Hefei Han’s Kereida performed reliably. This laser offers a valuable alternative to BPH surgeries.

The advancement of telemedicine technology has introduced innovative approaches to overcoming the challenges posed by uneven distribution of medical resources and the limited mobility of patients. Focusing on urodynamic study, this study presents the independent development of a remote urodynamic examination system. The device incorporates a communication framework utilizing Wi-Fi and internet technologies, enabling both remote control of the equipment and seamless data transmission. Experimental validation under remote communication conditions demonstrates that the average error in pressure measurement is below 1 cmH2O, and the error rate in peristaltic pump infusion is less than 5%, meeting the technical requirements set by the International Continence Society for urodynamic device. Furthermore, the integration of a detrusor overactivity identification model based on deep learning into the developed software establishes an intelligent auxiliary diagnostic function. The comprehensive remote UDS system developed in this study provides a practical solution to enhance patient experience and improve diagnostic efficiency for healthcare professionals. The incorporation of cutting-edge technologies, including Wi-Fi, internet communication, and deep learning, underscores the potential of this system in revolutionizing urodynamic assessments, paving the way for more accessible and efficient healthcare services.

PURPOSE:To intelligently diagnose whether there is bladder outlet obstruction (BOO) in female with decent detrusor contraction ability by focusing on urodynamic study (UDS) data. MATERIALS AND METHODS:We retrospectively reviewed the UDS data of female patients during urination. Eleven easily accessible urinary flow indicators were calculated according to the UDS data of each patient during voiding period. Eight diagnosis models based on back propagation neural network with different input feature combination were constructed by analyzing the correlations between indicators and lower urinary tract dysfunction labels. Subsequently, the stability of diagnostic models was evaluated by five-fold cross-validation based on training data, while the performance was compared on test dataset. RESULTS:UDS data from 134 female patients with a median age of 51 years (range, 27-78 years) were selected for our study. Among them, 66 patients suffered BOO and the remaining were normal. Applying the 5-fold cross-validation method, the model with the best performance achieved an area under the receiver operating characteristic curve (AUC) value of 0.949±0.060 using 9 UDS input features. The accuracy, sensitivity, and specificity for BOO diagnosis model in the testing process are 94.4%, 100%, and 89.3%, respectively. CONCLUSIONS:The 9 significant indicators in UDS were employed to construct a diagnostic model of female BOO based on machine learning algorithm, which performs preferable classification accuracy and stability.

So far there is no neoadjuvant therapy recommended by major hepatocellular carcinoma (HCC) guidelines. In other malignancies, ICIs in the neoadjuvant setting have shown better outcomes than in the adjuvant setting, and the combination of radiation therapy to ICIs incrementally improves the systemic response to ICIs. Neoadjuvant therapy of ICIs plus stereotactic body radiotherapy (SBRT) has shown promising results in several types of solid tumours but not HCC. This is a phase Ib clinical trial of neoadjuvant SBRT plus PD-1 (tislelizumab) in HCC patients (pts). Prior to resection, pts receive 8 Gy × 3 SBRT with 2 cycles of PD-1. HCC resection is scheduled 4 weeks after the second PD-1, followed by adjuvant PD-1 for up to 1 year. We plan to enrol 20 participants in this trial. The primary study endpoints include the surgery delay over 6 weeks or later, ORR on pre-resection imaging, pathologic response (pCR) rate, safety and tolerability of the sequential SBRT/PD-1. The secondary endpoints are DFS and OS rates every 3 or 6 months after the hepatic resection. By 10th May 2023, 11 pts were enrolled, all were BCLC A stage. One pt was excluded due to the protocol violation, in other 10 pts, one just starts the adjuvant therapy, two have completed the neoadjuvant therapy and waiting for the scheduled resection, all other 7 pts have completed the resection, and no surgery delay accrued; DCR reached 100% (RECIST: 1 PR, 6 SD; mRECIST: 1 CR, 2 PR, 3 SD, 1 CR+SD ); pCR was confirmed in two tumors; So far the safety of neoadjuvant SBRT+PD-1 was satisfied, grade 1 to 2 TRAEs, mainly anemia and white blood cell decreasing were common; grade 3 TRAE occurred in 3 pts (1 granulocytopenia and 2 elevated transaminase), but all well-tolerated. One pt developed recurrence 9 months after surgery (RF ablation), all other 6 pts are still in DFS.Table: 957PPt #age (Y)gendertumor size (cm)BCLC stageRECISTmRECISTinterval between 2nd PD-1 and surgerypCR (Y/N)TARE over grade 3(Y/N)survival170FS7:2.4×2.2ASDSD31NNRecurrence/RFA274MS4a:1.6; S2:1.2ASDS4a:CR; S2:SD28S4a: Y; S2:NNoDFS364MS8:1.8×1.6ASDSD28NYDFS451MS7/8:6.0×6.1APRPR26YYDFS570MS4/5:3.7×4.1ASDPR40NNDFS652MS6/7:4.1×4.0ASDCR28NYDFS770FS6:3.3ASDSD34NNDFS848FS8:2.2×1.7APRCRN956MS6:2.9×2.4AN1054MS6:4.8×3.3; S8:2.2×1.8AN Open table in a new tab The safety and clinical significance of radiotherapy plus PD-1 as the neoadjuvant therapy in HCC needs further exploration.

Second-line treatment options for patients with unresectable hepatocellular carcinoma (uHCC) are limited. Monotherapy with regorafenib or tislelizumab (an anti-PD-1 antibody) has shown clinical benefit for uHCC in the second-line setting. The present study explored the safety and efficacy of the tislelizumab plus regorafenib as second-line therapy for uHCC. This was a single-arm, investigator-initiated phase II trial. Patients with confirmed uHCC were enrolled to receive tislelizumab (200mg, q3w) plus regorafenib (80mg-160mg, daily, 3 weeks on/1 week off, every 4 weeks). The primary endpoint was safety and tolerability; Secondary endpoints included overall response rates (ORR), progression-free survival (PFS), and disease control rate (DCR) per mRECIST. A total of 28 patients were enrolled with median age of 59 years (range: 40-76) and 96% were men. Most common etiology of HCC was hepatitis B (n=26, 93%). 54% of patients were Barcelona Clinic Liver Cancer stage C. 67.9% of patients received prior treatment with tyrosine kinase inhibitors (TKIs; sorafenib [50%] or lenvatinib [17.9%]), and 21.4% received TKIs plus PD-1 antibody. ORR was 28.6% and DCR was 71.4%, with 3 pts having CR, 5 PR, and 12 SD. At the data cut-off date, the median PFS of the 28 pts was 6.4 months (95%Cl 90%, NA)), and the median OS was not reached. The most common treatment-related adverse events at any grade were rash (6/28;21%), hypertension (9/28;32%), hand-foot syndrome (18/28;64%) and fatigue (7/28;25%), which were mostly grade 1 or 2 in severity. This study indicated that tislelizumab plus regorafenib is an effective and well-tolerated therapeutic option for patients with uHCC.

Background The incidence of infections among cancer patients is as high as 23.2-33.2% in China. However, the lack of information and data on the number of antibiotics used by cancer patients is an obstacle to implementing antibiotic management plans. Aim This study aimed to investigate bacterial infections and antibiotic resistance in Chinese cancer patients to provide a reference for the rational use of antibiotics. Design This was a 5-year retrospective study on the antibiotic resistance of cancer patients. Methods In this 5-year surveillance study, we collected bacterial and antibiotic resistance data from 20 provincial cancer diagnosis and treatment centers and three specialized cancer hospitals in China. We analyzed the resistance of common bacteria to antibiotics, compared to common clinical drug-resistant bacteria, evaluated the evolution of critical drug-resistant bacteria and conducted data analysis. Findings Between 2016 and 2020, 216 219 bacterial strains were clinically isolated. The resistance trend of Escherichia coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, cefotaxime, piperacillin/tazobactam and imipenem was relatively stable and did not significantly increase over time. The resistance of Pseudomonas aeruginosa strains to all antibiotics tested, including imipenem and meropenem, decreased over time. In contrast, the resistance of Acinetobacter baumannii strains to carbapenems increased from 4.7% to 14.7%. Methicillin-resistant Staphylococcus aureus (MRSA) significantly decreased from 65.2% in 2016 to 48.9% in 2020. Conclusions The bacterial prevalence and antibiotic resistance rates of E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, S. aureus and MRSA were significantly lower than the national average.

Objective The purposes of this survey were to show the current situation of oncology critical care medicine in China, to understand the resource distribution of oncology critical care medicine, and to analyze and evaluate the existing resources and reserve capacity of oncology critical care medicine.Methods A general survey was conducted at the 36 member units of the Oncology Critical Care Medicine Committee of the Chinese Anti-cancer Association through e-mailed questionnaires. The census takers filled out the questionnaires with feedback. The survey covered 8 items: basic information on the hospital, basic profile of the ICU, personnel allocation, management status, technical skills, patient sources, equipment configuration and tumor- related treatment technology.Results The survey results involved information from 28 member units, all of which are tertiary hospitals, distributed in 20 provinces and 4 direct-controlled municipalities. The results are as follows. (1) The total ratio of ICU beds to hospital beds was 1.06%, and the average number of ICU beds was 16.36. (2) The ratio of ICU physicians to beds was approximately 0.62:1, and the ratio of nurses to beds was approximately 1.98:1. (3) According to the census of the population and GDP of different regions conducted by the State Statistics Bureau in 2017, the ratio of ICU beds for tumor patients to population was 4.55 beds per 10 million people, and the ratio of ICU beds to GDP was 8.00 beds per RMB 100 billion, on average. (4) The equipment configuration is relatively perfect, while the technical skills need to be improved.Conclusion The development of oncology critical care is becoming better, but there is still a certain gap compared with the ICU standards in China and the average level of the national ICU. It is urgent to develop oncology critical care medicine.

BACKGROUND:Erectile dysfunction (ED) is a common complication in patients with diabetes mellitus (DM) that severely affects the patients' quality of life. However, the effectiveness of oral phosphodiesterase type 5 inhibitors in these patients is poor. Sphingosine-1-phosphate (S1P) and S1P receptor 2 (S1PR2) are important factors regulating the Rho-kinase pathway, and understanding these factors may provide ideas for new therapeutic strategies for ED.OBJECTIVES:To investigate whether the S1PR2 receptor antagonist JTE-013 could improve DM-induced ED (DMED) in rats and to explore the potential mechanisms.MATERIALS AND METHODS:We used 50 male Sprague Dawley rats (8 weeks old) for this experiment. Type Ⅰ DM was induced in forty-two rats via streptozotocin administration; the rest of the rats served as controls. Eight weeks after DM induction, rats with ED were selected via an apomorphine test. Eight of them were injected intraperitoneally with JTE-013 each day for 4 weeks. The rest were fed under the same conditions for 4 weeks. Erectile function was measured by cavernous nerve electrostimulation. The expression levels of related signaling pathways were evaluated using Western blotting, real-time PCR, and immunohistochemistry.RESULTS:Erectile function was significantly impaired in the DMED group compared with the control group and was partially improved in the DMED + JTE-013 group. The expression of S1PR2 and the activity of the RhoA/ROCK/phospho-myosin phosphatase target subunit 1 (p-MYPT1) pathway proteins were higher in the DMED group than in the other two groups, and JTE-013 treatment significantly reduced the expression/activity of these proteins. Furthermore, the DMED group showed severe corporal fibrosis, a higher apoptotic index and increased activity in the TGF-β1/LIMK2/Cofilin pathway compared with the control group. JTE-013 supplementation significantly ameliorated these pathological changes.DISCUSSION AND CONCLUSION:JTE-013 supplementation partially improved erectile function in rats with DMED, likely by inhibiting smooth muscle contraction, corporal fibrosis, and apoptosis.

To investigate the detailed mechanism of erectile dysfunction (ED) induced by hyperhomocysteinaemia (HHcy) in rats and determine whether the Human Tissue Kallikrein 1 (hKLK1) might improve it, as we have proved the protective role of hKLK1 on erectile function in aged rats. We established a rat model of HHCy through dietary-rich methionine (Met) in male Sprague-Dawley (SD) rats. Male wild-type SD rats (WTR) and transgenic rats harboring the hKLK1 gene (TGR) were fed to 10 weeks of age. Then 24 WTRs were divided into control (n=8), the low-dose (4% Met, n=8), and the high-dose (7% Met, n=8). Another 8 age-matched TGRs with the high-dose formed the TGR+7%Met group. 30 days later, erectile function, level of total homocysteinaemia (tHcy), oxidative stress, endothelial function, cavernous nerve function and fibrosis of all groups were determined. hKLK1 in the TGR+7%Met group could greatly decrease the tHcy levels and improve ED induced by HHcy in rats. For the endothelial function, hKLK1 could preserve the endothelial cell-cell junction, enhance endothelial regeneration and activated the Akt/eNOS signaling pathway. Together with the promotion of hKLK1 on nNOS expression, the NO/cGMP signaling pathway activity was also increased. For the fibrosis, hKLK1 could preserve normal corpus cavernosum structure through inhibiting apoptosis and promoting autophagy on corpus cavernosum smooth muscle cells. In addition, hKLK1 also inhibited the fibrosis-related signaling pathway activity.

To investigate the effects of melatonin on rats with hyperhomocysteinemia (Hhcy)-related erectile dysfunction (HED), and the potential mechanisms via modulating oxidative stress and apoptosis. The rat model of hyperhomocysteinemia was induced by methionine-rich diet (7% methionine). Twelve rats fed a standard diet were regarded as a control group. Twenty-four rats were fed a methionine-rich diet. After a month, the rats with Hhcy were administered daily melatonin (n=12) in a dose of 10mg/kg or vehicle (n=12) intraperitoneally for 4 weeks. Rats as control group (n=12) were injected vehicle intraperitoneally for 4 weeks. Then, cavernous nerve electrostimulation was used to evaluate the erectile function of all rats. Total homocysteine (Hcy) levels in plasma were determined with ELISA. Fluorescent probe, ELISA and western blotting were performed to determine the levels of oxidative stress and related signaling pathway. TUNEL assay, RT-PCR and western blotting were performed to detect apoptosis. Compared with the control group and the melatonin-treated group, the HED group showed (1) lower erectile function: lower intracavernosal pressure (ICP)/mean arterial pressure(MAP) ratio and lower total ICP (area under curve, AUC); (2) higher levels of total Hcy in plasma (3) higher levels of ROS and MDA, but lower levels of SOD activity; (4)higher expression levels of Erk1/2/Nrf2/HO1 signaling pathway than the control group, but lower levels than melatonin-treated group; (5) higher levels of apoptosis proved by the expression levels of Bax, Bcl-2, caspase 3 and apoptosis index.

Previously, we have demonstrated that human tissue kallikrein 1 (hKLK1) improves age-related erectile dysfunction (ED). Autophagy has been implicated in age-related diseases, including ED. However, the molecular mechanisms underlying hKLK1-mediated amelioration of age-related ED via regulation of autophagy remains unknown. To explore the potential mechanism, male wild-type Sprague-Dawley rats (WTR) and transgenic rats harboring human KLK1 (TGR) were bred till 4 or 18 months of age and divided into three groups: young WTR (yWTR) as the control group, aged WTR (aWTR) group, and aged TGR (aTGR) group. The erectile function of each rat was evaluated using cavernous nerve electrostimulation. The ratio of intracavernous pressure/mean arterial pressure (ICP/MAP) and total ICP were also measured. Western blotting, immunohistochemistry, and transmission electron microscopy were performed to detect the levels of autophagy. The expression levels of related signaling pathways were determined by western blotting and immunohistochemistry. We found that hKLK1 improved the impaired erectile function of aged rats. Compared to the yWTR and aTGR groups, the aWTR group showed reduced smooth muscle/collagen ratio, fewer autophagosomes, and lower expression of Beclin 1 and LC3-II, which indicate impaired smooth muscle function and low level of autophagy in the smooth muscle cells. Moreover, the PI3K/Akt/mTOR signaling pathway, which is considered to be a negative regulator of autophagy, was upregulated in the aWTR group. hKLK1 may partially restore erectile function in aged transgenic rats by upregulating protective autophagy via the PI3K/Akt/mTOR pathway. These observations indicate that hKLK1 is a potential gene therapy candidate for age-related ED.

Considering 35%–90% of patients with diabetes mellitus (DM) suffer erectile dysfunction (ED), which starts about 10–15 years earlier than in the population without DM. Moreover, these patients showed a poor response to the first-line oral phosphodiesterase type 5 inhibitors. Thus, a novel treatment method is urgently needed. We tried to demonstrate whether melatonin could improve erectile function in diabetic rats and the underlying mechanisms. Type 1 DM was induced by using streptozotocin. 8 weeks later, we conducted an apomorphine test to confirm diabetes mellitus erectile dysfunction (DMED). Only rats with DMED (n=20) were administered melatonin (n=10) in a dose of 10mg/kg or vehicle (n=10) intraperitoneally each day for 4 weeks, rats as control group (n=10) were fed in the same condition for 4 weeks. Then, cavernous nerve electrostimulation was used to evaluate the erectile function of all rats. Histologic and molecular alterations of the corpus cavernosum also were analyzed. Furthermore, corpus cavernosum smooth muscle cells of rats were cultured under different conditions: normal glucose (NG), high glucose (HG), high glucose + melatonin (HG+M), high glucose + melatonin + melatonin receptor antagonist luzindole(HG+M+L), and related molecular biological parameter were detected.

Men with hyperlipidemia are more likely to have erectile dysfunction (ED) than those without hyperlipidemia, but the mechanisms are not fully understood. The aim of this study was to investigate the underlying mechanism of ED caused by hyperlipidemia. Fourteen 8-week-old Sprague-Dawley rats were randomly divided into two groups: a control group and a hyperlipidemia group (fed chow containing 4% cholesterol and 1% cholic acid). After 6 months, we assessed erectile function by performing cavernous nerve electrostimulation followed by intracavernosal pressure/mean arterial pressure measurements, as well as plasma lipid profile assessment in all rats. A transferase-mediated nick end labeling (TUNEL) assay, immunohistochemical staining and Western blotting were performed to determine the levels of apoptosis, autophagy and fibrosis in the penile tissue. Compared with the control group, the hyperlipidemia group exhibited: (i) increased plasma lipid levels; (ii) decreased erectile function; (iii) a decreased smooth muscle/collagen ratio; (iv) increased fibrosis; (v) increased apoptosis and decreased autophagy. Overall, hyperlipidemia may attenuate erectile function in rats by causing of cavernosal fibrosis.

Many researches had reported Human Tissue Kallikrein 1 (hKLK1) had numerous protective effects in cardiovascular system, while the detailed mechanism of hKLK1 protecting erectile function in aged rats is rarely mentioned. Male wild-type Sprague-Dawley rats (WTR) and transgenic rats harboring the hKLK1 gene (TGR) were fed to 4 and 18 months old and divided into three groups: young WTR (yWTR) as the control, aged WTR (aWTR) and aged TGR (aTGR). Erectile function of all rats was evaluated by cavernous nerve electrostimulation method. Expression levels of cAMP and cGMP were assessed, and nitric oxide synthase (NOS) activity and nitric oxide (NO) level were measured. Related signaling pathways were detected by western blot, immunohistochemistry and immunofluorescence. Erectile function of all rats was assessed through electrical stimulation on cavernous nerve showed that erectile function of the aWTR group was lower compared with those of other two groups. Expression levels of cAMP and cGMP, NOS activity and NO level were significantly lower than those of other two groups. Moreover, related signaling pathways of COX-2/PTGIS/cAMP and DDAH/ NOS/cGMP were also inhibited in the corpus cavernosum of rats in aWTR group.

The metabolic syndrome, a disease arising from the world-wide epidemic of obesity, is manifested as insulin resistance, hypertension, hyperlipidaemia, and diabetes. Metabolic Syndrome is a risk factor for erectile dysfunction (ED), but the underlying mechanisms are unclear. The aims of this study were to determine the underlying mechanisms of the metabolic syndrome-related ED. Sprague-Dawley rats rendered obese by feeding a very high fat diet for 6 months. Body weight, plasma insulin and glucose levels (insulin-resistance) and plasma lipid were assessed. Erectile responses were evaluated by determining mean arterial blood pressure (MAP) and intracavernosal pressure (ICP) with electrical stimulation of the cavernous nerve. Levels of protein expression were examined by Western Blot and Immunohistochemistry. The levels of body weight, blood glucose, plasma lipid were increased in metabolic syndrome rats when compared to those of control rats (P<0.05). The ratio of Maximum ICP-to-MAP (Max ICP/MAP) and the concentration of cyclic guanosine mono-phosphate (cGMP) was significantly decreased in metabolic syndrome ED rats, compared to that of age-matched control rats (P<0.05). Expression levels of p55, p110α, p-AKT1(T308) and eNOS were reduced, compared to those of control rats (P<0.05). Activation of the PI3K/AKT signaling cascade reversed these changes (each P<0.05).

The aim of this study was to investigate the underlying mechanism of androgen deficiency inducing corporal fibrosis, thereby causing erectile dysfunction (ED). Forty 12-week-old healthy male rats were divided randomly into four groups: normal control group (Control); castration group (Castration); the other 20 rats were castrated followed by testosterone (T) (orally) each day: castration + 10mg/kg T group (Castration + 10T) and castration + 20 mg/kg T group (Castration + 20T). After 8 weeks' treatment, the main outcome measures were the following: serum levels of T; the ratios of intracavernous pressure (ICP) to mean arterial pressure (MAP); histologic changes in penile smooth muscle cells; the Smad and non-Smad pathways; and extracellular matrix (ECM) protein deposition. Castration group showed lower level of T and ratio of ICP/MAP, reduced ratio of penile smooth muscle cells/collagen, increased extracellular matrix protein deposition, and a higher expression of the Smad and non-Smad pathways. Castration + 10T partially preserved erectile function and histology stabilisation. However, the Castration + 20T group showed significantly better erectile function and molecular changes. Better efficacy could be expected with ART of adequate dose. Androgen deficiency induces corporal fibrosis through activation of the Smad and non-Smad pathways, and accumulation of ECM proteins.