AI-based IsAb2.0 for antibody design.

Therapeutic antibody design has garnered widespread attention, highlighting its interdisciplinary importance. Advancements in technology emphasize the critical role of designing nanobodies and humanized antibodies in antibody engineering. However, current experimental methods are costly and time-consuming. Computational approaches, while progressing, faced limitations due to insufficient structural data and the absence of a standardized protocol. To tackle these challenges, our lab previously developed IsAb1.0, an in silico antibody design protocol. Yet, IsAb1.0 lacked accuracy, had a complex procedure, and required extensive antibody bioinformation. Moreover, it overlooked nanobody and humanized antibody design, hindering therapeutic antibody development. Building upon IsAb1.0, we enhanced our design protocol with artificial intelligence methods to create IsAb2.0. IsAb2.0 utilized AlphaFold-Multimer (2.3/3.0) for accurate modeling and complex construction without templates and employed the precise FlexddG method for in silico antibody optimization. Validated through optimization of a humanized nanobody J3 (HuJ3) targeting HIV-1 gp120, IsAb2.0 predicted five mutations that can improve HuJ3-gp120 binding affinity. These predictions were confirmed by commercial software and validated through binding and neutralization assays. IsAb2.0 streamlined antibody design, offering insights into future techniques to accelerate immunotherapy development.

Hepatic and extrahepatic metabolic modulation in hbv-related decompensated cirrhosis and acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) and decompensated cirrhosis (DC) are life-threatening syndromes that can develop at the end-stage of chronic hepatitis B virus (HBV) infection. Both ACLF and DC are complicated by hepatic and extrahepatic pathogeneses. To better understand the compartment-specific metabolic modulations related to their pathogenesis, HBV-DC, HBV-ACLF patients, and controls (30 each) were analyzed by metabolomics using portal (Port), hepatic vein (Hep), and peripheral (Peri) serum. Compartment ratios of metabolites (RatioHep/Port, RatioPeri/Hep, and RatioPort/Peri) were calculated. The liver tissues (10 per group) were analyzed using transcriptomics and metabolomics. An additional 75 patients with ACLF, 20 with DC, and 20 with liver cirrhosis (LC) were used to confirm oxlipid dysregulation. Both multi-omics datasets suggest suppressed energy, amino acid, and pyrimidine metabolism in the ACLF/DC liver. The serum metabolomic variations were contributed primarily by disease rather than sampling compartments, as both HBV-ACLF and HBV-DC patients demonstrated abnormal profiles of amino acids and peptides, indoles, purines, steroids, and benzimidazoles. In ACLF/DC patients, impaired hepatic metabolism resulted in a highly correlated hepatic and portal vein serum metabolome and release of inflammatory lipids and heme metabolites from the liver. HBV-ACLF showed higher RatioPeri/Hep of extrahepatic inflammatory oxlipids, while HBV-DC patients showed higher RatioPort/Peri of gut microbial metabolites. An inflammatory oxlipid outburst was confirmed in the early stages of HBV-ACLF. The inflammatory effects of the selected oxlipids were confirmed in monocytes. These findings support a synergy between liver-specific mechanisms and systemic inflammation in ACLF/DC development, and that pro-inflammatory oxlipids are metabolic signatures of early HBV-ACLF.

Predicting Breast Cancer Subtypes Using Magnetic Resonance Imaging Based Radiomics With Automatic Segmentation.

OBJECTIVE: The aim of the study is to demonstrate whether radiomics based on an automatic segmentation method is feasible for predicting molecular subtypes. METHODS: This retrospective study included 516 patients with confirmed breast cancer. An automatic segmentation-3-dimensional UNet-based Convolutional Neural Networks, trained on our in-house data set-was applied to segment the regions of interest. A set of 1316 radiomics features per region of interest was extracted. Eighteen cross-combination radiomics methods-with 6 feature selection methods and 3 classifiers-were used for model selection. Model classification performance was assessed using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RESULTS: The average dice similarity coefficient value of the automatic segmentation was 0.89. The radiomics models were predictive of 4 molecular subtypes with the best average: AUC = 0.8623, accuracy = 0.6596, sensitivity = 0.6383, and specificity = 0.8775. For luminal versus nonluminal subtypes, AUC = 0.8788 (95% confidence interval [CI], 0.8505-0.9071), accuracy = 0.7756, sensitivity = 0.7973, and specificity = 0.7466. For human epidermal growth factor receptor 2 (HER2)-enriched versus non-HER2-enriched subtypes, AUC = 0.8676 (95% CI, 0.8370-0.8982), accuracy = 0.7737, sensitivity = 0.8859, and specificity = 0.7283. For triple-negative breast cancer versus non-triple-negative breast cancer subtypes, AUC = 0.9335 (95% CI, 0.9027-0.9643), accuracy = 0.9110, sensitivity = 0.4444, and specificity = 0.9865. CONCLUSIONS: Radiomics based on automatic segmentation of magnetic resonance imaging can predict breast cancer of 4 molecular subtypes noninvasively and is potentially applicable in large samples.

Transcriptome sequencing and experiments reveal the effect of formyl peptide receptor 2 on liver homeostasis.

BACKGROUND: Formyl peptide receptor 2 (Fpr2) is an important receptor in host resistance to bacterial infections. In previous studies, we found that the liver of Fpr2-/- mice is the most severely damaged target organ in bloodstream infections, although the reason for this is unclear. AIM: To investigate the role of Fpr2 in liver homeostasis and host resistance to bacterial infections. METHODS: Transcriptome sequencing was performed on the livers of Fpr2-/- and wild-type (WT) mice. Differentially expressed genes (DEGs) were identified in the Fpr2-/- and WT mice, and the biological functions of DEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) en-richment analysis. Quantitative real time-polymerase chain reaction (qRT-PCR) and western blot (WB) analyses were used to further validate the expression levels of differential genes. Cell counting kit-8 assay was employed to investigate cell survival. The cell cycle detection kit was used to measure the distribution of cell cycles. The Luminex assay was used to analyze cytokine levels in the liver. The serum biochemical indices and the number of neutrophils in the liver were measured, and hepatic histopathological analysis was performed. RESULTS: Compared with the WT group, 445 DEGs, including 325 upregulated genes and 120 downregulated genes, were identified in the liver of Fpr2-/- mice. The enrichment analysis using GO and KEGG showed that these DEGs were mainly related to cell cycle. The qRT-PCR analysis confirmed that several key genes (CycA, CycB1, Cdc20, Cdc25c, and Cdk1) involved in the cell cycle had significant changes. The WB analysis confirmed a decrease in the expression of CDK1 protein. WRW4 (an antagonist of Fpr2) could inhibit the proliferation of HepG2 cells in a concentration dependent manner, with an increase in the number of cells in the G0/G1 phase, and a decrease in the number of cells in the S phase. Serum alanine aminotransferase levels increased in Fpr2-/- mice. The Luminex assay measurements showed that interleukin (IL)-10 and chemokine (C-X-C motif) ligand (CXCL)-1 levels were significantly reduced in the liver of Fpr2-/- mice. There was no difference in the number of neutrophils, serum C-reactive protein levels, and liver pathology between WT and Fpr2-/- mice. CONCLUSION: Fpr2 participates in the regulation of cell cycle and cell proliferation, and affects the expression of IL-10 and CXCL-1, thus playing an important protective role in maintaining liver homeostasis.

Computed tomography-based COVID-19 triage through a deep neural network using mask-weighted global average pooling.

Background: There is an urgent need to find an effective and accurate method for triaging coronavirus disease 2019 (COVID-19) patients from millions or billions of people. Therefore, this study aimed to develop a novel deep-learning approach for COVID-19 triage based on chest computed tomography (CT) images, including normal, pneumonia, and COVID-19 cases. Methods: A total of 2,809 chest CT scans (1,105 COVID-19, 854 normal, and 850 non-3COVID-19 pneumonia cases) were acquired for this study and classified into the training set (n = 2,329) and test set (n = 480). A U-net-based convolutional neural network was used for lung segmentation, and a mask-weighted global average pooling (GAP) method was proposed for the deep neural network to improve the performance of COVID-19 classification between COVID-19 and normal or common pneumonia cases. Results: The results for lung segmentation reached a dice value of 96.5% on 30 independent CT scans. The performance of the mask-weighted GAP method achieved the COVID-19 triage with a sensitivity of 96.5% and specificity of 87.8% using the testing dataset. The mask-weighted GAP method demonstrated 0.9% and 2% improvements in sensitivity and specificity, respectively, compared with the normal GAP. In addition, fusion images between the CT images and the highlighted area from the deep learning model using the Grad-CAM method, indicating the lesion region detected using the deep learning method, were drawn and could also be confirmed by radiologists. Conclusions: This study proposed a mask-weighted GAP-based deep learning method and obtained promising results for COVID-19 triage based on chest CT images. Furthermore, it can be considered a convenient tool to assist doctors in diagnosing COVID-19.

Evaluation of BDE-47-induced neurodevelopmental toxicity in zebrafish embryos.

There are growing concerns about the neurodevelopmental toxicity of polybrominated diphenyl ethers (PBDEs), but the toxicological phenotypes and mechanisms are not well elucidated. Here, zebrafish (Danio rerio) were exposed to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) from 4 to 72 h post-fertilization (hpf). The results showed that BDE-47 stimulated the production of dopamine and 5-hydroxytryptamine, but inhibited expression of Nestin, GFAP, Gap43, and PSD95 in 24 hpf embryos. Importantly, we unraveled the inhibitory effects of BDE-47 on neural crest-derived melanocyte differentiation and melanin syntheses process, evidenced by disrupted expression of wnt1, wnt3, sox10, mitfa, tyrp1a, tyrp1b, tryp2, and oca2 gene in 72 hpf embryos and decreased tyrosinase activities in embryos at 48 and 72 hpf. The transcriptional activities of myosin VAa, kif5ba, rab27a, mlpha, and cdc42 genes, which are associated with intracellular transport process, were also disturbed during zebrafish development. Ultimately, these alterations led to fast spontaneous movement and melanin accumulation deficit in zebrafish embryos upon BDE-47 exposure. Our results provide an important extension for understanding the neurodevelopmental effects of PBDEs and facilitate the comprehensive evaluation of neurotoxicity in embryos.

lncRNAPVT1 targets miR-152 to enhance chemoresistance of osteosarcoma to gemcitabine through activating c-MET/PI3K/AKT pathway.

BACKGROUND: LncRNA PVT1 has been reported to be involved in a variety of biological processes, including cell proliferation, cell differentiation and cancer progression. However, the mechanism by which LncRNA PVT1 contributes to chemoresistance of osteosarcoma cell, has not been fully elucidated. METHODS: We first generatedLncRNA PVT1-overexpressed MG63 cells and LncRNA PVT1 knockdown MG63/DOX cells. Then, we examined the effect of LncRNA PVT1 on cell viability and colony formation ability by MTT assay and soft agar assay, respectively. In addition, we performed flow cytometry analysis to detect apoptosis induced by GEM. Dual luciferase reporter assay and RIP were used to confirmed the interaction between LncRNA PVT1 and miR-152. Finally, we determined protein level of c-MET, p-PI3K, and p-AKT by westernblot. RESULTS: LncRNA PVT1 overexpression promoted cell proliferation and exhibited the anti-apoptotic property in LncRNA PVT1-overexpressing MG63 cells treated with gemcitabine. While, LncRNA PVT1-depleted MG63/DOX cells treated with gemcitabine exhibited significant lower survival rate and high percentage of apoptosis. Next, we found that LncRNA PVT1 could target and downregulated the level of miR-152. Interestingly, miR-152 greatly rescued the biological outcomes of LncRNA PVT1 not only in MG63 but also in MG63/DOX cells. We observed that LncRNA PVT1 markedly induced PI3K/AKT pathway activation, which was abolished by miR-152 mimics overexpression. Finally, c-MET inhibitor was used to confirm the essential role of c-MET in LncRNA PVT1 and miR-152-regulated PI3K/AKT signaling. CONCLUSION: We showed thatlncRNA PVT1 played a contributory role in chemoresistance of osteosarcoma cells through c-MET/PI3K/AKT pathway activation, which was largely dependent on miR-152. Our findings advance our understanding of how lncRNA PVT1 promotes chemoresistance of osteosarcoma cells and facilitate development of novel strategies for treating osteosarcoma.

Elimination of melanoma by sortase A-generated TCR-like antibody-drug conjugates (TL-ADCs) targeting intracellular melanoma antigen MART-1.

Most tumor-associated proteins are located inside tumor cells and thus are not accessible to current marketed therapeutic monoclonal antibodies or their cytotoxic conjugates. Human leukocyte antigen (HLA) class I can present peptides derived from intracellular tumor-associated proteins and somatically mutated proteins on the cell's surface, forming an HLA/peptide complex as tumor-specific antigens for T cell receptor (TCR) recognition. Therefore, HLA-mediated presentation of intracellular tumor antigen peptides provides a viable way to distinguish tumor cells from normal cells, which is important for broadening antigen selection, especially for antibody-drug conjugates (ADCs) regarding their highly cytotoxic payload. We applied sortase A-mediated conjugation to develop TCR-like ADCs (i.e., EA1 HL-vcMMAE) targeting intracellular MART-1 protein, a melanocyte-differentiating antigen specific for metastatic melanomas, via the cell surface HLA-A2/MART-126-35 peptide complex. Homogenous EA1 HL-vcMMAE (drug to antibody ratio of 4) efficiently eliminated melanoma cells in xenograft mouse models with no obvious toxicity at the therapeutic dosage. Trametinib, an MEK inhibitor serving as an HLA expression enhancing agent, augmented the TL-ADCs' efficacy both in vitro and in vivo by upregulating MART-126-35 peptide presentation, thus providing a strategy for overcoming the limitation of antigen presentation level for TL-ADCs. Hence, our findings validate the strategy of using sortase A-generated TL-ADCs to target tumor-specific intracellular proteins, with or without agents present, to increase presenting TCR epitope peptides.

[Establishment of a rat model of low calcium diet related hyperoxaluria].

OBJECTIVE: To establish a rat model of low calcium diet related hyperoxaluria and explore its features. METHODS: By means of randomized blocks design, totally 24 SD male rats were divided into low calcium diet group, medium calcium diet group, and high calcium diet group. Each group was sequentially fed on different calcium diets for 3 days. The urinary volume within 24 hours was recorded, the consistency of urinary oxalate by high-efficiency liquid chromatography, and the consistency of urine creatinine by automatic biochemical analyzer. The consistency was corrected to the output of urinary oxalate of rats in 24 hours, and the results were evaluated by repeated measurement of variance analysis and multivariate analysis of variance. RESULTS: The output of urinary oxalate of rats in 24 hours varied with time (F=7.893, P0.05). The output of urinary oxalate of rats in 24 hours varied with group division (F=3.565, P<0.05). The output of urinary oxalate in 24 hours in three groups on the third day was significantly higher than that on the first day (P<0.05). CONCLUSION: By controlling the calcium intake, we successfully established the model of low calcium diet related hyperoxaluria in rat.

Prognostic value of Her-2/neu and clinicopathologic factors for evaluating progression and disease-specific death in Chinese men with prostate cancer.

BACKGROUND: Her-2/neu gene overexpression has been found in several malignancies, and is associated with poor prognosis; while its role in the tumorigenesis and progression of prostate cancer (PCa) is still controversial. This study aimed to evaluate the prognostic value of Her-2/neu protein expression and clinicopathologic factors in antiandrogen-treated Chinese men with PCa for disease progression and PCa-specific death. METHODS: Her-2/neu protein expression was determined using immunohistochemistry (IHC) in specimens collected from 124 prostate biopsies and transurethral resection of prostate (TURP) from seven prostate cancer patients. RESULTS: Her-2/neu protein expression was 0, 1+, 2+, and 3+ in 40 (30.5%), 8 (6.1%), 67 (51.1%), and 16 (12.2%) cases, respectively. Her-2/neu protein expression showed significant correlation as judged by Gleason score (P = 0.049), clinical tumor-node-metastases (cTNM) stage (P = 0.018) and disease progression (P = 0.001), but did not correlate with prostate-specific antigen (PSA) (P = 0.126) or PCa-specific death (P = 0.585). PSA (P = 0.001), Gleason score (P = 0.017), cTNM (P = 0.000) and Her-2/neu protein expression (P = 0.001) had prognostic value for evaluating the progression of PCa in univariate analysis. In Kaplan-Meier plots, both Gleason score (P = 0.035) and cTNM (P = 0.013) correlated with PCa-specific death. In multivariate analysis, only cTNM was significant for both disease progression (P = 0.001) and PCa-specific death (P = 0.031). CONCLUSIONS: Her-2/neu protein expression is significantly correlated with Gleason score, cTNM and disease progression, although it is not an independent predictor of disease progression and PCa-specific death. cTNM staging serves as an independent prognostic factor for disease progression and PCa-specific death.

Lack of direct androgen regulation of PDE5 expression.

It has been reported that penile PDE5 expression was under androgen regulation. However it remained unknown whether the observed change in PDE5 expression in castrated animals was under direct androgen regulation or due to changes in smooth muscle content. In the present study we showed that castration of rats caused a reduction of penile size and cavernous smooth muscle content. Immunostaining detected concomitant reduction of PDE5 and alpha smooth muscle actin (alpha-SMA) expression in the corpus cavernosum of castrated rats. Real-time PCR and Western blotting detected no change of PDE5 expression when normalized with alpha-SMA expression in castrated rats. Androgen receptor (AR) expression was increased while PDE5 expression remained unchanged in DHT-treated rat cavernous smooth muscle cells (CSMC). Prostate specific antigen (PSA) promoter activity was upregulated while PDE5A promoter activity remained unchanged in DHT-treated CSMC. Thus, PDE5 expression was not under direct androgen regulation.

[Clinical questionnaires about benign prostatic hyperplasia].

OBJECTIVE: s To assess the understanding degree of urologists for benign prostatic hyperplasia (BPH) and the clinical characteristics of BPH patients. METHODS: The questionnaires was distributed to urologists and patients in 119 hospitals over the country, respectively. The urologist survey was mainly focused on the questions of BPH progression and therapeutic model. The patient survey was mainly focused on the questions of patient's age, symptom features and the preference to receiving treatment. RESULTS: The evaluations based on 289 completed urologist questionnaires and 4253 completed patient questionnaires showed that 98.6% of urologists agreed that BPH was a progressive disease but there were still some differences in understanding the risk factors for BPH progression. Additionally, 98.1% of patients were diagnosed to be moderate or severe BPH, nocturia was the most frequent symptom. In the treatment for BPH, both the urologists and patients concerned about how to improve the system rapidly. CONCLUSIONS: This study is the first questionnaires specifically to the urologists and BPH patients, the results would reflect the situations of BPH diagnosis and treatment in China and would be helpful to the development of BPH guideline.

[Efficacy and safety of long-acting gonadotropin-releasing hormone analogue in the treatment for metastatic prostate cancer].

OBJECTIVE: To evaluate the efficacy and safety of gonadotropin-releasing hormone analogue (GnRHa) triptorelin 11.25 mg 3-month sustained release formulations in the treatment of metastatic prostate cancer. METHODS: From January 2004 to March 2006, a randomized, parallel-controlled, multicenter clinical trial was conducted. One hundred and twenty-seven patients with documented metastatic prostate cancer were randomized to receive one injection of the 11.25 mg formulation triptorelin (n = 65) or three injections at 28-day intervals of the 3.75 mg formulation (n = 62). Changes from baseline of TPSA, prostate volume, testosterone, LH, FSH, PRL and estradiol were assessed over 3 months. Changes of the metastatic lesions were also observed and evaluated. The occurrences of adverse events were evaluated as well. RESULTS: After 3 months treatment, total PSA level decreased significantly from baseline both in 11.25 mg group and 3.75 mg group. At 30, 60 and 90 days, TPSA (median level) declined from 164.55 microg/L into 11.34, 4.12, 3.89 microg/L in 11.25 mg group, and from 101.38 microg/L into 6.88, 2.41, 2.57 microg/L in control group respectively. The patients ratio with over 90% decreasing from TPSA baseline were 78.6% and 75.5% respectively in two groups (P = 0.700). Prostate volume were also decreased significantly in both groups, median volume declined from 48.0 mm(3) into 21.5 mm(3) in 11.25 mg group and from 45.0 mm(3) into 21.0 mm(3) in 3.75 mg group. No significant differences were found between the two groups in changes of TPSA (P = 0.601) and prostate volume (P > 0.05). Both formulations were able to induce castration levels, 0.31 microg/L in 11.25 mg group and 0.26 microg/L in 3.75 mg group (P > 0.05). 13.8% and 17.7% of adverse events were recorded respectively in two groups, and no differences were found (P = 0.547). CONCLUSION: As a new long-acting sustained release formulation, triptorelin 11.25 mg is comparable to triptorelin 3.75 mg formulation in the aspect of efficacy and safety for the treatments of metastatic prostate cancer.

[A proteomic study of the serum proteins in BPH and HGPIN patients].

OBJECTIVE: To evaluate two-dimensional gel electrophoresis (2DGE) and mass spectrometry in the studies of the serum proteins expressed in patients with BPH and those with high-grade prostatic intraepithelial neoplasm (HGPIN). METHODS: We extracted serum proteins from BPH and HGPIN patients by 2DGE and cut the differentially expressed interesting protein spots from the gel. Then we digested the proteins, obtained the peptide mass fingerprint by mass spectrometry and identified the proteins through database retrieval. RESULTS: We successfully achieved the 2DGE maps of the serum proteins from the BPH and HGPIN patients, obtained 1 421-1 532 protein spots from the 2D map of HGPIN and 1 466-1 778 from that of BPH. Based on peptide mass fingerprinting, 9 of the protein spots were identified. Serum amyloid A was found to be expressed in the HGPIN group, but weakly or not at all in the BPH. CONCLUSION: Proteomics can be applied to the study of the serum proteins in BPH and HGPIN patients. It can afford experimental evidence for the early diagnosis and development HGPIN, promote the search of functional and specific proteins of prostate diseases and shed new light on the network mechanisms of the problems.

[Erectile function in male kidney transplant recipients and effects of different methods of renal arterial anastomosis].

OBJECTIVE: To evaluate erectile function in men with renal failure before and after kidney transplantation and the effects of different methods of renal arterial anastomosis. METHODS: Fifty-five married males, aged 22-50 years, who had received kidney transplantation at least one year before and whose serum creatinine was under 200 micromol/L , were selected in the study. The end-to-end revascularization to the internal iliac artery was accomplished in 39 of them, and the end-to-side revascularization to the external iliac artery was conducted in 16. Their erectile function was investigated according to the International Index of Erectile Function-5 (IIEF-5) before kidney transplantation and 3, 6 and 9 months after it. The effects of different methods of renal arterial anastomosis were evaluated and hypophyseal hormones determined in 25 of them. RESULTS: IIEF-5 was higher in the patients 3, 6 and 9 months after transplantation than before it (P < 0.05) and 6 and 9 months after transplantation than 3 months after it (P < 0.05) , so was it in the patients with less than 12 months hemodialysis than those with over 12 months (P < 0.05) and in the patients with end-to-side revascularization to the external iliac artery than those with end-to-end revascularization to the internal iliac artery (P < 0.05). The differences between the level of hypophyseal hormones and that of sex hormones before transplantation were significant (P < 0.05). CONCLUSION: Erectile function and the level of hypophyseal hormones were improved after kidney transplantation, and the patients who received end-to-side revascularization to the external iliac artery experienced better erectile function recovery than those who underwent end-to-end revascularization to the internal iliac artery.

[Vascular factors in the pathogenesis of diabetic erectile dysfunction].

Diabetic erectile dysfunction (DED) is a multifactor syndrome, which involves vascular disease, neuropathy, metabolic control, nutrition, endocrine disorders, psychogenic factors, and anti-diabetes drugs. Among all these factors, vascular disease plays a very important role. In the development of diabetic vasculopathy, some vasomotion factors and growth factors undergo conspicuous changes, which may be significantly correlated with the development of diabetic erectile dysfunction.

[Progress of gene therapy for erectile dysfunction].

Gene therapy is currently investigated in animal studies for treating erectile dysfunction (ED), and is affording an conspicuous therapeutic possibility for the treatment of ED, especially in L-arg-NO-cGMP pathway, ion channel, the protection of nerves and endothelia in erectile tissues. However there still exist so many problems for gene therapy to be effectively applied to the clinical treatment of ED. This review aims to examine the experimental efforts in recent years and tries to give a brief introduction to the new approaches in the field of ED researches.

[Retroperitoneoscopic dismembered pyeloplasty in children].

OBJECTIVE: To evaluate the technique and the clinical efficacy of Retroperitoneoscopic dismembered pyeloplasty in children. METHODS: Retroperitoneoscopic dismembered pyeloplasty was performed on 17 patients of pediatric ureteropelvic junction (UPJ) obstruction, age ranging from 3 - 10 years. All patients had radiographic evidence of obstruction with signs, symptoms or deterioration of renal function. RESULTS: All of the 17 operations were performed successfully, and no serious complications occurred during and after the operations. Average operating time was 4.3 hours, which decreased with surgeon experience. Average blood loss was 38 ml, mean postoperative stay was 4.6 d. Only one case had postoperative urine leakage. With a mean follow-up of 14 months, all patients were free of obstruction on follow-up radiographic imaging. CONCLUSIONS: Retroperitoneoscopic dismembered pyeloplasty is a safe, effective and minimally invasive procedure for treatment of UPJ obstruction in children, and it can be used as an alternative to open surgery.

Effects of coffee and caffeine on bladder dysfunction in streptozotocin-induced diabetic rats.

AIM: To explore the effects and mechanisms of caffeine and coffee on bladder dysfunction in streptozotocin-induced diabetic rats. METHODS: Sprague-Dawley male rats were divided randomly into 4 groups: control, diabetes mellitus (DM), DM with coffee treatment, and DM with caffeine treatment. The diabetic rat was induced by intraperitoneal injection of streptozotocin (60 mg/kg). After 7 weeks of treatment with coffee and caffeine, cystometrogram, contractile responses to electrical field stimulation (EFS) and acetylcholine (ACh), and cyclic AMP (cAMP) concentration of the bladder body and base were measured. RESULTS: The bladder weight, volume threshold for micturition and post-void residual volume (PVR) in the diabetic rats were significantly higher compared to those in the control animals. Coffee or caffeine treatment significantly reduced the bladder weight, bladder capacity and PVR in the diabetic rats. DM caused significant decreases in cAMP concentration of the bladder and coffee and caffeine caused upregulation of cAMP content in the diabetic bladder. In addition, coffee and caffeine tended to normalize the altered detrusor contractile responses to EFS and ACh in the diabetic rats. CONCLUSION: These results indicate that caffeine and coffee may have beneficial effects on bladder dysfunction in the early stage of diabetes by increasing cAMP content in the lower urinary tract, recovering the micturition reflex and improving the detrusor contractility.