Research progress of natural product evodiamine-based antitumor drug design strategies / 药学学报

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

Recent advances in chemical fluorescent probes sensitive to tumor microenvironments / 药学学报

Cancer seriously threatens human life and health, it is urgent for the development of rapid detection, precise localization and effective treatment of tumors. Chemical fluorescent probes that are sensitive to tumor-specific microenvironments have important significance in tumor theranostics and a variety of such probes have been developed. In this review, we classified chemical fluorescent probes that are sensitive to tumor microenvironments according to biological characteristics and microenvironmental changes while combining spectroscopy or response mechanisms, and systematically introduced the research progress of chemical fluorescent probes with sensitivity to hypoxia, low polarity, high viscosity, abnormal pH values and abundant reactive oxygen species in tumor microenvironments, in order to provide references for the development and applications of these probes.

Progress of potential therapeutic targets and small molecule ligands of anti-colorectal cancer pathogenic Fusobacterium nucleatum / 药学学报

The composition of intestinal microflora is closely related to the occurrence and development of colorectal cancer (CRC). Among them, Fusobacterium nucleatum (Fn) has been proved directly related to the recurrence, metastasis and chemotherapy resistance of CRC. Therefore, it is of great significance for the prevention and treatment of colorectal cancer by the exploration potential anti-Fn drug targets and discovery small molecule drugs. However, no selective anti-Fn small molecule inhibitors have been reported so far as well as their anti-Fn thereby "anti-Fn further anticancer" mechanisms are unclear. Herein, this article reviews the potential therapeutic targets and small molecule ligands of Fn in order to provide a reference for the development of anti-Fn and anti-CRC small molecule drugs.

Research progress of cyclic peptide synthesis strategy and its application in new drug development / 药学学报

Protein-protein interaction (PPI) plays an important role in the regulation of life. Most of the PPI interfaces are large and discontinuous, and it is difficult for small molecules to specifically bind to them. Peptides are critical in PPI surface interactions due to their higher affinity and specificity. However, peptides have some defects such as easy hydrolysis by protease and poor membrane permeability. Due to good biocompatibility and chemical diversity, cyclic peptides play an important role in drug discovery. Therefore, the development of efficient cyclic peptide construction methods has become a frontier issue in peptide drug research. In recent years, a series of new progresses have been made in the synthesis strategy and the application of cyclic peptides, providing powerful technical tools for the research and development of cyclic peptide drugs. In this review, the synthesis strategies of cyclic peptides and their application will be reviewed from four aspects: synthesis strategies, property improvement, biological activity and prospect.

A novel robust nomogram based on peripheral monocyte counts for predicting lymph node metastasis of prostate cancer / 亚洲男科学杂志(英文版)

Accurate methods for identifying pelvic lymph node metastasis (LNM) of prostate cancer (PCa) prior to surgery are still lacking. We aimed to investigate the predictive value of peripheral monocyte count (PMC) for LNM of PCa in this study. Two hundred and ninety-eight patients from three centers were divided into a training set (n = 125) and a validation set (n = 173). In the training set, the independent predictors of LNM were analyzed using univariate and multivariate logistic regression analyses, and the optimal cutoff value was calculated by the receiver operating characteristic (ROC) curve. The sensitivity and specificity of the optimal cutoff were authenticated in the validation cohort. Finally, a nomogram based on the PMC was constructed for predicting LNM. Multivariate analyses of the training cohort demonstrated that clinical T stage, preoperative Gleason score, and PMC were independent risk factors for LNM. The subsequent ROC analysis showed that the optimal cutoff value of PMC for diagnosing LNM was 0.405 × 109 l

Research progress on the correlation between interleukin-18 and chronic periodontitis / 口腔疾病防治

@#Chronic periodontitis is an infectious disease caused by plaque as the initiating factor. Clinically, it manifests as irreversible loss of hard tissue, leading to the destruction of surrounding periodontal tissue, including the deep periodontal pocket, loss of attachment, and finally, tooth loss. Interleukin-18 (IL-18) can promote inflammation and regulate immune function and plays an important role in mediating the host immune response and inflammatory response. An increase in IL-18 in vivo can induce the production of interferon and inflammatory factors, such as interleukin, tumor necrosis factor and matrix metalloproteinase, thus mediating the dual reaction of immunity and inflammation. These inflammatory factors are involved in the occurrence and development of chronic periodontitis. Many clinical studies have shown that the levels of IL-18 in serum, saliva, gingival crevicular fluid and gingival tissue samples of patients with chronic periodontitis may be positively correlated with the severity of periodontitis; however, as a candidate gene, IL-18 is involved in the susceptibility polymorphism of periodontitis. Understanding how to quantify the level of IL-18 in clinical studies and apply it to diagnostic tools and new sites identified by new methods (genome-wide association studies and omics research) will also deepen our understanding of the pathogenesis of IL-18 in chronic periodontitis and provide new ideas for future precision medicine and the formulation of personalized programs. In this paper, the structure, biological function and association between IL-18 and periodontitis are reviewed.

Phosphoglycerate mutase 1 knockdown inhibits prostate cancer cell growth, migration, and invasion / 亚洲男科学杂志(英文版)

Phosphoglycerate mutase 1 (PGAM1) is upregulated in many cancer types and involved in cell proliferation, migration, invasion, and apoptosis. However, the relationship between PGAM1 and prostate cancer is poorly understood. The present study investigated the changes in PGAM1 expression in prostate cancer tissues compared with normal prostate tissues and examined the cellular function of PGAM1 and its relationship with clinicopathological variables. Immunohistochemistry and Western blotting revealed that PGAM1 expression was upregulated in prostate cancer tissues and cell lines. PGAM1 expression was associated with Gleason score (P = 0.01) and T-stage (P = 0.009). Knockdown of PGAM1 by siRNA in PC-3 and 22Rv1 prostate cancer cell lines inhibited cell proliferation, migration, and invasion and enhanced cancer cell apoptosis. In a nude mouse xenograft model, PGAM1 knockdown markedly suppressed tumor growth. Deletion of PGAM1 resulted in decreased expression of Bcl-2, enhanced expression of Bax, caspases-3 and inhibition of MMP-2 and MMP-9 expression. Our results indicate that PGAM1 may play an important role in prostate cancer progression and aggressiveness, and that it might be a valuable marker of poor prognosis and a potential therapeutic target for prostate cancer.

Serum inhibin B and varicocele: An update / 中华男科学杂志

Inhibin B, a glycoprotein produced predominantly by Sertoli cells and preferentially suppressing the production and secretion of follicle-stimulating hormone (FSH) in the pituitary, is closely related to spermatogenesis. Varicocele is the abnormal dilatation and tortuosity of the pampiniform plexus veins, which may contribute to spermatogenic dysfunction and male infertility. More and more evidence has shown that the level of serum inhibin B is negatively correlated with the severity of varicocele. Determination of the inhibin B level may help assess the severity of spermatogenic dysfunction of the patient and predict the outcomes of varicocele repair and therefore has a potential application value in the diagnosis and treatment of varicocele.

Quantitative and comparative proteomics analysis in clear cell renal cell carcinoma and adjacent noncancerous tissues by 2-D DIGE / 南方医科大学学报

<p><b>OBJECTIVE</b>To identify specific protein markers for renal cell carcinoma detection and diagnosis, as well as develop new potential therapeutic targets of the disease.</p><p><b>METHODS</b>We used two-dimensional difference in-gel electrophoresis (2-D DIGE) technique conjunction with mass spectrometry (MS) for the identification of significant differentially expressed proteins between 15cases of paired clear cell renal cell carcinoma (ccRCC) and adjacent normal renal tissues. The protein spots were considered as differentially expressed if a 1.5-fold altered expression level was observed (Student's t test, P value<0.05).</p><p><b>RESULTS</b>Of the 27 differentially expressed protein spots, 26 proteins were successfully identified. 11 proteins up-regulated in renal cell carcinoma,15 proteins down-regulated. Among them Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial (ACDSB), Aldose 1-epimerase (GALM), Peroxiredoxin-4 (PRDX4), Macrophage-capping protein (CAPG), Beta-defensin 107 (D107A), Microfibril-associated glycoprotein 4 (MFAP4) were first time screening as new differential expressed proteins by protomic study in renal cell carcinoma.</p><p><b>CONCLUSIONS</b>2-D DIGE is a useful technique for screening and analysis differential expressed proteins in renal cell carcinoma. These new differently expressed proteins may be useful for development new molecular markers for the tumor.</p>

Synthesis and evaluation of new 3-aminooxazolidin-2-one derivatives for inhibiting bacterial quorum sensing / 国际药学研究杂志

Objective To develop some 3-aminooxazolidin-2-one derivatives with bacteria quorum sensing(QS) inhibitory activity. Methods Using (2-hydroxyethyl) hydrazine as raw material, we finished the synthesis through cyclization, condensation, hydrolysis and condensation reaction, and evaluated their inhibition of QS via Chromobacterium violaceum. Results Eight compounds were synthesized and their structures were confirmed by 1H NMR and MS characterization. Compounds Z2 had inhibitory effect against QS. Conclusion None of the eight synthesized compounds have been reported before and the synthetic route is reliable. Compounds Z2 have inhibitory effect against QS.

Updated evaluation and intervention of adolescent varicocele / 中华男科学杂志

Some physiological and ethical problems make it difficult to obtain semen samples from adolescents with varicocele (VC) and to directly evaluate their fertility. Therefore we can only rely on indirect methods to assess the influence of VC on the future fertility of the adolescent patients. Most of the VC adolescents may have normal semen parameters in the adulthood. Thus whether and when to intervene in adolescent VC remain a controversy in andrology. Physical examination is the most common method for screening adolescent VC and ultrasonography is very effective for its diagnosis and evaluation. Other important diagnostic indicators include the widely accepted testicular atrophy index, recently proposed peak retrograde venous flow, total testis volume, and scrotal temperature. Based on the latest literature, this review offers some proposals for the evaluation and intervention of adolescent VC.

Vasectomy does not increase the risk of prostate cancer in Chinese men: A meta-analysis / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the correlation of vasectomy with the risk of prostate cancer in Chinese men.</p><p><b>METHODS</b>We systematically searched the databases CNKI, VIP, Wanfang, PubMed, Embase, and Cochrane Library for the literature relating the relationship between vasectomy and the risk of prostate cancer in Chinese males up to December 2014. According to the inclusion and exclusion criteria, two investigators independently selected the eligible publications, evaluated their quality, and extracted relevant information, followed by a meta-analysis with the software STATA 12.0.</p><p><b>RESULTS</b>Nine studies were included in the analysis involving 1 202 cases of prostate cancer and 4,496 controls. Random-effect model analysis revealed no statistically significant correlation between vasectomy and the risk of prostate cancer (OR = 1.05; 95% CI 0.62-1.79), with an obvious heterogeneity (P < 0.001, I2 = 85.7%). No significant publication bias was found among the included studies (Egger, P = 0.824; Begg, P = 0.348).</p><p><b>CONCLUSION</b>The results of our meta-analysis do not support the association of vasectomy with the increased risk of prostate cancer in Chinese population.</p>

Reproductive hormone levels and relevant parameters in middle-aged and older men in the urban area of Nanjing / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the status of male reproductive health among middle-aged and older men in the urban area of Nanjing.</p><p><b>METHODS</b>We collected the laboratory results of 884 middle-aged and older men aged 55 - 89 years from the Xuanwu District of Nanjing present for routine physical examinations, including those of blood routine tests, liver and kidney function, blood glucose, blood lipid, and total prostate specific antigen (TPSA), as well as such reproductive hormone indexes as total serum testosterone (TT), free serum testosterone (fT), and sex hormone binding globulin (SHBG). We also obtained the above reproductive hormone indexes from 119 young and middle-aged men aged 20 - 39 years as controls.</p><p><b>RESULTS</b>Aging-related changes were found in the 50 percentiles of all the reproductive hormones and relevant parameters but those of TT and E2, with gradual increases in LH, FSH and SHBG and decreases in fT, TSI and fTI. Comparison of reproductive hormones and relevant parameters by Mann-Whitney U test did not show any statistically significant differences in the TT level between any two of the five age groups (20 - 39, 55 - 59, 60 - 69, 70 - 79, and > or = 80 yr) (P > 0.05) except between the control and > or = 80 yr groups and the 60 - 69 and > or = 80 yr groups (P < 0.05), nor in the E2 level between any two groups, nor in the levels of LH and FSH except between the 55 - 59 and 60 - 69 yr groups and the 70 - 79 and > or = 80 yr groups, and nor in the levels of fT and TSI except between the 55 - 59 and 60 - 69 yr groups. However, there were significant differences in the levels of SHBG and fTI between any two age groups. Spearman correlation analysis revealed that fT, TSI, and fTI were correlated negatively with aging and LH (P < 0.05, I r I > 0.5) but weakly positively with cholesterol, blood glucose and hemoglobin (P < 0.05, /r/ < 0.5), SHBG and LH positively with aging, SHBG weakly negatively with blood glucose and hemoglobin, LH weakly negatively with hemoglobin, and TT weakly negatively with aging but positively with hemoglobin.</p><p><b>CONCLUSION</b>The levels of serum testosterone, particularly that of fT, declined with aging in middle-aged and older men in the urban area of Nanjing, which may contribute to abnormal lipid metabolism, low hemoglobin and high blood glucose.</p>

A meta-analysis of holmium laser enucleation of the prostate for benign prostatic hyperplasia / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the effectiveness and safety of holmium laser enucleation of the prostate (HoLEP) and transurethral resection of the prostate (TURP)/open prostatectomy (OP) in the treatment of bladder outlet obstruction (BOO) secondary to benign prostatic hyperplasia (BPH).</p><p><b>METHODS</b>We searched Medline, Cochrane Library, Embase, Wanfang and CBM for randomized controlled trials (RCT) comparing HoLEP with TURP/OP. Comparable data were extracted from eligible studies and pooled for meta-analysis using RevMan5.1.</p><p><b>RESULTS</b>Nine RCTs were included in this study, 6 comparing HoLEP with TURP, and the other 3 comparing HoLEP with OP. Meta-analysis showed that, compared with TURP, HoLEP was associated with shorter hospital stay and catheterization time, less hemoglobin loss, longer operative time, and better improvement in international prostate symptom score (IPSS) , peak urinary flow rate (Qmax) and post void residual (PVR) , but the incidences of postoperative urethral stricture and urinary incontinence had no statistically significant difference between the two. Compared with OP, HoLEP showed shorter hospital stay and catheterization time, a lower rate of blood transfusion, longer operative time, and removal of fewer tissues, but the two procedures exhibited no significant differences in either the improvement of IPSS and Qmax or the incidence of urethral stricture.</p><p><b>CONCLUSION</b>HoLEP is a minimally invasive technique, safe and highly effective for the treatment of BOO secondary to BPH, with its advantages of lower peri-operative morbidity and faster recovery over TURP and OP. However, more high-quality RCTs with larger sample sizes and longer follow-ups need to be carried out to obtain better evidence.</p>

Construction, expression and location of eukaryotic expression vector CMV-FLAG-RB in human prostate cancer PC-3 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct an eukaryotic recombinant expression vector for retinoblastoma 1 gene (RB-1) and investigate the role of RB-1 in prostate cancer.</p><p><b>METHODS</b>The coding sequence of RB-1 gene tagged with FLAG was amplified from the plasmid CMV-RB by PCR method. The fragment was cloned into CMV expression vector and identified by restriction enzyme digestion and sequence analysis. Western Blotting was used to detect RB-1 expression and immunofluorescence was used to observe RB-1 distribution in PC-3 cells transfected with the recombinant.</p><p><b>RESULTS</b>The expression vector CMV-FLAG-RB was successfully constructed as confirmed by PCR, endonuclease digestion and DNA sequence analysis. RB-1 protein was highly expressed and showed a nuclear distribution in PC-3 cells transfected with the recombinant.</p><p><b>CONCLUSIONS</b>The eukaryotic expression vector for RB-1 has been successfully constructed and can be efficiently expressed in PC-3 cells. The expression of RB-1 is located in the cell nuclei.</p>

Retroperitoneal laparoscopic surgery combined with ureteroscopic lithotomy for treatment of renal and ureteral calculi / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the feasibility of retroperitoneal laparoscopic surgery combined with ureteroscopic lithotomy through the pelvis for treatment of renal and ureteral calculi.</p><p><b>METHODS</b>In February 2010, 2 patients with renal and ureteral calculi underwent retroperitoneal laparoscopic surgery combined with ureteroscopic lithotomy through the pelvis.</p><p><b>RESULTS</b>The operation time in these two cases was 70 and 80 min, and the volume of intraoperative blood loss was about 20 ml. The exposure was excellent, and the patient recovered rapidly without complications or residual calculi.</p><p><b>CONCLUSION</b>Retroperitoneal laparoscopic surgery combined with ureteroscopic lithotomy through the pelvis is feasible for treatment of renal and ureteral calculi.</p>

Synchronous squamous cell carcinoma of the renal pelvis and squamous cell carcinoma of the ureter: report of two cases and review of literature / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the clinicopathological characteristics of synchronous squamous cell carcinoma (SCC) of the renal pelvis and SCC of the ureter.</p><p><b>METHODS</b>The clinical data of two cases of synchronous SCC of the renal pelvis and SCC of the ureter were retrospectively reviewed and analyzed. In case 1, a 68-year-old man with hematuria for a month, imaging modalities revealed a right renal pelvis tumor and a right distal ureter tumor. The patient underwent nephroureterectomy and excision of the bladder cuff. Case 2, a 60-year-old man with the complaint of lower abdominal pain and left flank pain for a month, was diagnosed as left distal ureteral stone in another hospital. Ureterolithotomy was performed and a ureteral tumor was found at the lower site of the stone intraoperatively. The pathological report demonstrated SCC, and the patient was transferred to our hospital for further treatment. We found a left renal mass invading the left hemicolon during surgery, and nephroureterectomy was performed with a bladder cuff excision, left hemicolon resection, and also complete lymph node dissection. Neither of patients received adjuvant radiotherapy/chemotherapy.</p><p><b>RESULTS</b>Moderately differentiated SCC was reported in both of renal pelvis and ureter in case 1 and the tumor invaded the subepithelial connective tissue in the renal pelvis and superficial muscle in the ureter. In case 2, moderately differentiated SCC of the left renal pelvis with colon metastasis and poorly differentiated SCC of the ureter was reported with two retroperitoneal lymph node metastases. The two patients died from tumor recurrence and metastasis 5 and 6 months after the surgery, respectively.</p><p><b>CONCLUSION</b>Synchronous SCC of the renal pelvis and SCC of the ureter are rare and has high likeliness of early recurrence and metastasis, often with poor prognosis.</p>

Differential expressions of the receptor for advanced glycation end products in prostate cancer and normal prostate / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the differential expressions of the receptor for advanced glycation end products (RAGE) in the tissues of prostate cancer and normal prostate, and to find the role of RAGE in the pathogenesis of prostate cancer.</p><p><b>METHODS</b>We collected the tissue of prostate cancer and that of normal prostate from the same patient, and compared the differential expressions of RAGE at the tissue, protein and mRNA levels between prostate cancer and normal prostate tissues of 10 patients by immunohistochemistry, Western blot and real-time quantitative PCR.</p><p><b>RESULTS</b>Immunohistochemistry exhibited a significantly higher expression of RAGE in the prostate cancer tissue than in the normal prostate tissue; Western blot showed that the RAGE protein expression was 2.13 times higher in the former than in the latter (P < 0.05); and real-time quantitative PCR revealed the RAGE mRNA expression of the former to be 4.2 times that of the latter (P < 0.05).</p><p><b>CONCLUSION</b>RAGE may play an important role in the pathogenesis and progression of prostate cancer.</p>

Diagnosis and treatment of transverse testicular ectopia: a case report and literature review / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the etiology, diagnosis and treatment of transverse testicular ectopia (TTE).</p><p><b>METHODS</b>A case of TTE was treated with orchidopexy.</p><p><b>RESULTS</b>Six months after the operation, both of the two testes were in proper positions with normal vascular supply.</p><p><b>CONCLUSION</b>TTE is a rare congenital abnormality of the male reproductive system with unknown etiology, and surgical correction remains the best option for treatment.</p>

Suprapubic puncture: preferable to transurethral catheterization for pressure-flow determination in BPH patients / 中华男科学杂志

<p><b>OBJECTIVE</b>To compare suprapubic puncture and transurethral catheterization for pressure-flow determination during voiding in BPH patients.</p><p><b>METHODS</b>Both suprapubic puncture and transurethral catheterization were used for pressure-flow determinations during voiding in 23 BPH patients at the mean age of 69.3 years (range 57-77 years) and the related parameters were compared by t-test.</p><p><b>RESULTS</b>Compared with transurethral catheterization, suprapubic puncture increased Qmax by 1.19 mn/s (P <0.05) and MMC by 66.61 ml (P <0.01) , and reduced the pressure of detrusor at Qmax (Pdet, Qmax) by 10.57 cmH2O (P < 0.05), URA by 11.39 cmH2O (P < 0.01) and AG by 12.94 (P < 0.01). Either according to the Schäfer diagram or with AG > 40 as the diagnostic standard, there were 16 (69.6%) cases of bladder outlet obstruction (BOO) in the suprapubic puncture group and 20 (87.0%) in the transurethral catheterization group.</p><p><b>CONCLUSION</b>In pressure-flow determination during voiding, suprapubic puncture and transurethral catheterization each have its own advantages and disadvantages, but the former is preferred for BPH patients. As for other patients, it all depends on specific conditions.</p>