A detection model of testis-derived circular RNAs in serum for predicting testicular sperm retrieval rate in non-obstructive azoospermia patients.

BACKGROUND: Microdissection testicular sperm extraction is an effective method to retrieve sperm from non-obstructive azoospermia patients. However, its successful rate is less than 50%. OBJECTIVES: To identify the predictive value of circular RNAs in serum for sperm retrieval rate in non-obstructive azoospermia patients. MATERIALS AND METHODS: 180 non-obstructive azoospermia patients were recruited in this study, including 84 individuals with successful sperm retrieval and 96 individuals with failed sperm retrieval. Our study contained two phases. First, 20 patients, selected from the 180 patients, were included in screening cohort. In this cohort, the top 20 circular RNAs from our previous testicular circRNA profiles were verified between successful and failed sperm retrieval groups using real-time polymerase chain reaction. Six circular RNAs with the most significantly different expressions were selected for further verification. Second, the 180 patients were included as discovery cohort to verify the six circular RNAs. Circular RNAs were extracted from serum in each participant. Logistic regression analysis was further performed to identify the predictive value and the area under the curve analysis was used to evaluate diagnostic efficiency, sensitivity, and specificity. RESULTS: Six circular RNAs including hsa_circ_0058058, hsa_circ_0008045, hsa_circ_0084789, hsa_circ_0000550, hsa_circ_0007422, and hsa_circ_0004099 showed aberrant expressions between the successful and failed sperm retrieval group. In addition, both single-circular RNA panels and multi-circular RNA panels were finally verified to be significant in predicting sperm retrieval rate. Notably, multi-circular RNAs panels demonstrated better predictive abilities compared with single-circRNA panels, and the combined panel of six-circular RNAs (risk score = 1.094×hsa_circ_0058058+0.697×hsa_circ_0008045+0.718×hsa_circ_0084789-0.591×hsa_circ_0000550-0.435×hsa_circ_0007422-1.017×hsa_circ_0004099-1.561) exhibited the best predictive ability in the present study with an AUC of 0.977, a sensitivity of 91.7% and a specificity of 86.5%. A higher risk score indicated a higher risk of failure in sperm retrieval. DISCUSSION AND CONCLUSION: Our study was the first to report that testis-derived circular RNAs in serum have the ability to predict sperm retrieval rate in non-obstructive azoospermia patients, whether it is a single-circular RNA or a combination of multi-circular RNAs.

[Identification of key points and differentiation planning strategies of Shantou, Guangdong, China]. / å¹¿ä¸œçœæ±•å¤´å¸‚ç”Ÿæ€ä¿®å¤å ³é”®ç‚¹è¯†åˆ«ä¸Žå·®å¼‚åŒ–è§„åˆ’.

Territorial ecological restoration planning is a carrier process for carrying out territorial space regulation and ecological restoration. However, current urban planning efforts only focus on ecological processes, and fail to coordinate the development of both ecology and society. Taking Shantou, a city in Guangdong Province, as an example, we focused on the identification of ecological restoration nodes and the development of differentiated planning strategies from a comprehensive ecological-social perspective. By considering ecosystem integrity, we extracted the ecological corridors and key points by identifying ecological sources and constructing resistance surfaces, constructed an ecological recreation service evaluation system from the social perspective in terms of recreational allocation and recreational value to identify key areas for recreation services, and obtained different types of ecological restoration strategies by synthesizing the results of ecology and recreation. The results showed that there were 136 ecological corridors and 77 ecological nodes in Shantou, with a total length of 380.58 km. The most important recreation areas were the coastline, several inland bays, and wetland tidal flats, with an area of 33.78 km2 and accounting for 1.6% of the total area. Low-level recreation areas was the largest, accounting for 57.3% of the total area. We proposed the composite strategy of "recreation expansion & fishery development", the connectivity strategy of "ecological construction & corridor connection", and the protection strategy of "vegetation restoration & development restriction". This study would provide a comprehensive analysis path for the ecological protection and restoration planning of coastal cities, and would help promote the practicality and maximizing the comprehensive benefits of territorial ecological restoration planning.

High ligation of the hernia sac in open nonmesh inguinal herniorrhaphy is an important cause of iatrogenic vas deferens injury.

Vasectomy damage is a common complication of open nonmesh hernia repair. This study was a retrospective analysis of the characteristics and possible causes of vas deferens injuries in patients exhibiting unilateral or bilateral vasal obstruction caused by open nonmesh inguinal herniorrhaphy. The site of the obstructed vas deferens was intraoperatively confirmed. Data, surgical methods, and patient outcomes were examined. The Anderson-Darling test was applied to test for Gaussian distribution of data. Fisher's exact test or Mann-Whitney U test and unpaired t-test were used for statistical analyses. The mean age at operation was 7.23 (standard deviation [s.d.]: 2.09) years and the mean obstructive interval was 17.72 (s.d.: 2.73) years. Crossed (n = 1) and inguinal ( n = 42) vasovasostomies were performed. The overall patency rate was 85.3% (29/34). Among the 43 enrolled patients (mean age: 24.95 [s.d.: 2.20] years), 73 sides of their inguinal regions were explored. The disconnected end of the vas deferens was found in the internal ring on 54 sides (74.0%), was found in the inguinal canal on 16 sides (21.9%), and was found in the pelvic cavity on 3 sides (4.1%). Location of the vas deferens injury did not significantly differ according to age at the time of hernia surgery ( ≥ 12 years or <12 years) or obstructive interval (≥15 years or <15 years). These results underscore that high ligation of the hernial sac warrants extra caution by surgeons during open nonmesh inguinal herniorrhaphy.

10-7 M genistein partially alleviates 10-7 M MEHP unfavorable effects in a new modified fetal rat testis culture system.

Background: Recent studies revealed that some common endocrine-disrupting chemicals (EDCs) including phthalates and phytoestrogens may exhibit low-dose effects properties. However, how low dose of these EDCs and their mixture would affect fetal rat testis development still needs further investigation. Moreover, testis organ culture system also needs further modification to provide an effective tool for ex vivo EDCs study. Methods: We firstly modified the agarose organ culture system, in which fetal rat testes were cultured for 4 days (d1 to d4) on agarose gels held by Millicell inserts. Then we used the modified agarose culture system to study the combined effects of multiple EDCs exposure. 15.5 dpc fetal rat testes were isolated and treated with vehicle, MEHP (0.1 µmol/L), GEN (0.1 µmol/L) or MEHP (0.1 µmol/L) + GEN (0.1 µmol/L). Parameters concerning testicular cell development and function were evaluated, trying to gain insight into the early molecular events after multiple EDCs exposure. Results: The development of somatic, germ cells and seminiferous tubule in 15.5 dpc fetal rat testis was better sustained in the modified agarose culture system. Based on the modified system, we found that MEHP at 0.1 µmol/L induced alterations in gonocyte markers, antioxidative enzyme activity as well as transient reduction of testosterone production, accompanied by mitochondria swelling in gonocytes and Sertoli cells. No obvious morphological and histological alterations were observed in all treated groups. However, coadministration of genistein at 0.1 µmol/L partially alleviated MEHP-induced fetal testis damage ex vivo through enhancement of antioxidative action. MEHP at low dose still showed weak endocrine disrupting properties but did not exhibit typical low-dose effects. Conclusion: Our findings indicated that the modified agarose culture system could better mimic testicular microenvironment without obvious hypoxic cell damage. Furthermore, low dose of MEHP induced mild disruption to fetal testis development, cotreatment of genistein at low dose attenuated MEHP induced fetal testis injuries in part by balancing redox state, indicating that low dose of genistein may partially protect fetal testis from phthalates induced injury.

[Efficacy of biofeedback and electrical stimulation therapy combined with Sabale capsules for chronic prostatitis / chronic pelvic pain syndrome].

Objective: To investigate the clinical effect of biofeedback and electrical stimulation therapy (BFES) combined with Sabale capsules (SC) on chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS). METHODS: A total of 140 outpatients meeting CP/CPPS diagnostic and research criteria in the Second Affiliated Hospital of Xi'an Jiaotong University were randomly divided into groups A (blank control), B (BFES intervention), C (SC intervention) and D (BFES+SC intervention), 35 cases in each group. The patients in group A were left untreated, while those in groups B, C and D received BFES, SC and BFES+SC, respectively, all for 12 weeks. Then the patients were followed up at 30 days after treatment and the urinary flow rate and NIH-CPSI scores were obtained and compared with the baseline. RESULTS: In comparison with the baseline, the total NIH-CPSI scores after intervention were significantly decreased in groups B, (ï¼»27.30 ± 2.44ï¼½ vs ï¼»19.43 ± 2.33ï¼½), C (ï¼»26.77 ± 2.54ï¼½ vs ï¼»19.40 ± 2.75ï¼½) and D (ï¼»27.67 ± 3.69ï¼½ vs ï¼»15.57 ± 1.94ï¼½) (all P < 0.05), and so were the individual item scores in pain or discomfort (ï¼»12.50 ± 1.94ï¼½ vs ï¼»9.40 ± 2.01ï¼½, ï¼»11.93 ± 1.64ï¼½ vs ï¼»9.23 ± 1.96ï¼½, and ï¼»12.33 ± 2.20ï¼½ vs ï¼»7.50 ± 1.55ï¼½), urination symptoms (ï¼»6.07 ± 1.57ï¼½ vs ï¼»3.83 ± 1.05ï¼½, ï¼»5.97 ± 1.33ï¼½ vs ï¼»3.77 ± 1.14ï¼½, and ï¼»6.20 ± 1.88ï¼½ vs ï¼»2.87 ± 0.94ï¼½), quality of life (QOL) (ï¼»8.73 ± 1.62ï¼½ vs ï¼»6.20 ± 1.42ï¼½, ï¼»8.87 ± 1.25ï¼½ vs ï¼»6.40 ± 1.59ï¼½, and ï¼»9.13 ± 1.70ï¼½ vs ï¼»5.20 ± 1.40ï¼½) (all P < 0.05), while the maximum urinary flow rate (Qmax) was remarkably increased (ï¼»15.72 ± 2.38ï¼½ vs ï¼»19.73 ± 2.85ï¼½, ï¼»16.20 ± 2.44ï¼½ vs ï¼»19.46 ± 2.48ï¼½, and ï¼»15.83 ± 2.52ï¼½ vs ï¼»22.49 ± 2.76ï¼½) (all P < 0.05), and so was the average urinary flow rate (Qavg) (ï¼»9. 282 ± 1.52ï¼½ vs ï¼»11.27 ± 1.95ï¼½, ï¼»8.97 ± 1.25ï¼½ vs ï¼»11.16 ± 1.74ï¼½, and ï¼»9.20 ± 1.36ï¼½ vs ï¼»13.50 ± 2.30ï¼½) (all P < 0.05). The decrease in NIH-CPSI total and item scores and increase in Qmax and Qavg after treatment were more significant in group D than in B and C (P < 0.05), but showed no statistically significant difference between groups B and C (P > 0.05). Nor was any significant change observed in the above parameters in group A after treatment ( P > 0.05). CONCLUSIONS: Biofeedback and electrical stimulation therapy combined with Sabale capsules can alleviate urination dysfunction, pelvic floor tension myalgia and other symptoms and significantly improve the QOL of CP/CPPS patients.

Oxidative Stress Disrupted Prepubertal Rat Testicular Development after Xenotransplantation.

In the past two decades, testicular tissue grafting and xenografting have been well established, with the production of fertilization-competent sperm in some studies. However, few studies have been carried out to observe the development of grafted prepubertal testicular tissue of rats and compare the biological differences between in situ testis and grafted testis. In this study, we established the prepubertal testicular tissue xenografting model using a 22-day-old rat and evaluated certain parameters, including testicular histology, testosterone production, and ultrastructure of the grafted testes. We also assessed gene expression of cell proliferation markers, testicular cell markers, and antioxidative defense system. Our results showed that 47 days after transplantation, intratesticular testosterone concentration was not significantly altered; however, cell proliferation, spermatogenesis, and Sertoli cell markers in the transplanted testes were significantly disrupted compared with the control group, accompanied by aggravated apoptosis and oxidative damage. Moreover, the transplanted testes showed smaller tubular diameter and disrupted spermatogenic epithelium with apparent vacuoles, distorted and degenerated germ cells with obscure nuclear margin, and no spermatids in the center of the tubules. Although testis xenografting has been extensively tested and attained great achievement in other species, the prepubertal rat testicular tissue xenografting to immunodeficient mice exhibited obvious spermatogenesis arrest and oxidative damage. The protocol still needs further optimization, and there are still some unknown factors in prepubertal rat testes transplantation.

Clinical recommendations for perioperative immunotherapy-induced adverse events in patients with non-small cell lung cancer.

Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large-scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy.

Expert consensus on resection of chest wall tumors and chest wall reconstruction.

Chest wall tumors are a relatively uncommon disease in clinical practice. Most of the published studies about chest wall tumors are usually single-center retrospective studies, involving few patients. Therefore, evidences regarding clinical conclusions about chest wall tumors are lacking, and some controversial issues have still to be agreed upon. In January 2019, 73 experts in thoracic surgery, plastic surgery, science, and engineering jointly released the Chinese Expert Consensus on Chest Wall Tumor Resection and Chest Wall Reconstruction (2018 edition). After that, numerous experts put forward new perspectives on some academic issues in this version of the consensus, pointing out the necessity to further discuss the points of contention. Thus, we conducted a survey through the administration of a questionnaire among 85 experts in the world. Consensus has been reached on some major points as follows. (I) Wide excision should be performed for desmoid tumor (DT) of chest wall. After excluding the distant metastasis by multi-disciplinary team, solitary sternal plasmacytoma can be treated with extensive resection and adjuvant radiotherapy. (II) Wide excision with above 2 cm margin distance should be attempted to obtain R0 resection margin for chest wall tumor unless the tumor involves vital organs or structures, including the great vessels, heart, trachea, joints, and spine. (III) For patients with chest wall tumors undergoing unplanned excision (UE) for the first time, it is necessary to carry out wide excision as soon as possible within 1-3 months following the previous surgery. (IV) Current Tumor Node Metastasis staging criteria (American Joint Committee on Cancer) of bone tumor and soft tissue sarcoma are not suitable for chest wall sarcomas. (V) It is necessary to use rigid implants for chest wall reconstruction once the maximum diameter of the chest wall defect exceeds 5 cm in adults and adolescents. (VI) For non-small cell lung cancer (NSCLC) invading the chest wall, wide excision with neoadjuvant and/or adjuvant therapy are recommended for patients with stage T3-4N0-1M0. As clear guidelines are lacking, these consensus statements on controversial issues on chest wall tumors and resection could possibly serve as further guidance in clinical practice during the upcoming years.

COVID-19 and early-stage lung cancer both featuring ground-glass opacities: a propensity score-matched study.

BACKGROUND: Radiological manifestations of coronavirus disease 2019 (COVID-19) featured ground-glass opacities (GGOs), especially in the early stage, which might create confusion in differential diagnosis with early lung cancer. We aimed to specify the radiological characteristics of COVID-19 and early lung cancer and to unveil the discrepancy between them. METHODS: One hundred and fifty-seven COVID-19 patients and 374 early lung cancer patients from four hospitals in China were retrospectively enrolled. Epidemiological, clinical, radiological, and pathological characteristics were compared between the two groups using propensity score-matched (PSM) analysis. RESULTS: COVID-19 patients had more distinct symptoms, tended to be younger (P<0.0001), male (P<0.0001), and had a higher body mass index (P=0.014). After 1:1 PSM, 121 matched pairs were identified. Regarding radiological characteristics, patients with a single lesion accounted for 17% in COVID-19 and 89% in lung cancer (P<0.0001). Most lesions were peripherally found in both groups. Lesions in COVID-19 involved more lobes (median 3.5 vs. 1; P<0.0001) and segments (median 6 vs. 1; P<0.0001) and tended to have multiple types (67%) with patchy form (54%). Early lung cancer was more likely to have a single type (92%) with oval form (66%). Also, COVID-19 and early lung cancer either had some distinctive features on computed tomography (CT) images. CONCLUSIONS: Both COVID-19 and early lung cancers showed GGOs, with similar but independent features. The imaging characteristics should be fully understood and combined with epidemiological history, pathogen detection, laboratory tests, short-term CT reexamination, and pathological results to aid differential diagnosis.

Low Dose of Genistein Alleviates Mono-(2-Ethylhexyl) Phthalate-Induced Fetal Testis Disorder Based on Organ Culture Model.

Mono-(2-ethylhexyl) phthalate (MEHP) and genistein have been classified as endocrine-disrupting chemicals (EDCs) which interfere with the differentiation and development of the male reproductive system. However, how these two EDCs would affect fetal rat testis development at a low dose was rarely studied. In this study, we established the organ culture system and applied it to evaluate testicular effects following multiple EDC exposure at a low dose. 15.5 days postcoitum fetal rat testes were dissected, cultured, and exposed to vehicle (control), GEN (1 µmol/L, G), MEHP (1 µmol/L, M), or GEN (1 µmol/L)+MEHP (1 µmol/L, G+M). Testicular cell markers, testosterone concentration, redox state, testicular histology, and testicular ultrastructure were evaluated. Our results showed that a low dose of MEHP suppressed the development of Sertoli cells, Leydig cells, and gonocytes by triggering oxidative injuries, which was consistent with the ultrastructural findings. However, coadministration of genistein at a low dose could partially attenuate MEHP-induced fetal testis damage through antioxidative action. Cotreatment of genistein at a low dose may have a promising future on its protecting role for attenuating other EDC-induced reproductive disorders during early life. Based on the results, it can be speculated that dietary intake of isoflavones may make the fetal testis less susceptible to phthalate-induced injury.

Longitudinal serum autoantibody repertoire profiling identifies surgery-associated biomarkers in lung adenocarcinoma.

BACKGROUND: Autoantibodies against tumor associated antigens are highly related to cancer progression. Autoantibodies could serve as indicators of tumor burden, and have the potential to monitor the response of treatment and tumor recurrence. However, how the autoantibody repertoire changes in response to cancer treatment are largely unknown. METHODS: Sera of five lung adenocarcinoma patients before and after surgery, were collected longitudinally. These sera were analyzed on a human proteome microarray of 20,240 recombinant proteins to acquire dynamic autoantibody repertoire in response to surgery, as well as to identify the antigens with decreased antibody response after tumor excision or surgery, named as surgery-associated antigens. The identified candidate antigens were then used to construct focused microarray and validated by longitudinal sera collected from a variety of time points of the same patient and a larger cohort of 45 sera from lung adenocarcinoma patients. FINDINGS: The autoantibody profiles are highly variable among patients. Meanwhile, the autoantibody profiles of the sera from the same patient were surprisingly stable for at least 3 months after surgery. Six surgery-associated antigens were identified and validated. All the five patients have at least one surgery-associated antigen, demonstrating this type of biomarkers is prevalent, while specific antigens are poorly shared among individuals. The prevalence of each antigen is 2%-14% according to the test with a larger cohort. INTERPRETATION: To our knowledge, this is the first study of dynamically profiling of autoantibody repertoires before/after surgery of cancer patients. The high prevalence of surgery-associated antigens implies the possible broad application for monitoring of tumor recurrence in population, while the low prevalence of specific antigens allows personalized medicine. After the accumulation and analysis of more longitudinal samples, the surgery-associated serum biomarkers, combined as a panel, may be applied to alarm the recurrence of tumor in a personalized manner. FUNDING: Research supported by grants from National Key Research and Development Program of China Grant (No. 2016YFA0500600), National Natural Science Foundation of China (No. 31970130, 31600672, 31670831, and 31370813), Open Foundation of Key Laboratory of Systems Biomedicine (No. KLSB2017QN-01), Science and Technology Commission of Shanghai Municipality Medical Guidance Science &Technology Support Project (16411966100), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20172005), Shanghai Municipal Commission of Health and Family Planning Outstanding Academic Leaders Training Program (2017BR055) and National Natural Science Foundation of China (81871882).

Traditional Chinese Medicine Treatment as Adjuvant Therapy in Completely Resected Stage IB-IIIA Non-Small-Cell Lung Cancer: Study Protocol for a Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial.

Adjuvant chemotherapy (AC) has been proven to yield an approximately 5% improvement in 5-year survival for patients with early-stage non-small-cell lung cancer. With such small gains in survival, the optimal treatment regimen remains to be established. Traditional Chinese medicine (TCM) treatment in combination with AC is frequently used in China. The efficacy and safety of this integrated approach should be scientifically evaluated. We present the rationale and study design of the Combined Adjuvant Chemotherapy and Traditional Chinese Medicine (ACTCM) trial (ChiCTR-IPR-16009062). The ACTCM trial, a prospective multicenter double-blind randomized placebo-controlled study, will recruit 312 patients overall from 5 clinical research centers in China. Within 6 weeks of the thoracic surgery, eligible participants with stages IB-IIIA non-small-cell lung cancer will be randomly assigned in a 1:1 ratio to either the treatment or control group. Patients in the treatment group will receive AC combined with TCM herbal treatment for 4 cycles, then TCM herbal plus injection treatment for 4 cycles. Patients in the control group will receive AC combined with TCM placebo for 4 cycles and then TCM placebo for 4 cycles. Treatment will be discontinued if disease progression or unacceptable toxicity occurs. The primary end point is 2-year disease-free survival. Secondary end points include disease-free survival and quality of life. Other end points are TCM symptoms, performance status, and safety of the regimens. Recruitment started in October 2016 and is ongoing.

Dynamic changes of different phenotypic and genetic circulating tumor cells as a biomarker for evaluating the prognosis of RCC.

BACKGROUND: Circulating tumor cells (CTCs) and relevant autophagy Beclin-1 genes expression are critical biomarkers for tumorigenesis and tumor progress. Here we investigated the relationship of dynamic changes of CTCs and Beclin-1 expression of CTCs with renal cell carcinoma (RCC) prognosis. MATERIALS AND METHODS: A total of 69 patients with RCC were enrolled and divided into two groups based on the postoperative status of distant metastasis, including metastasis-free group (n = 58) and metastatic group (n = 11). Demographic characteristics of each patient were recorded in detail. All 69 enrolled patients had received multiple CTC tests and peripheral blood samples were obtained at three different time points (1 day before operation, 6 months and 12 months after operation). Peripheral blood samples were drawn before each time point and CTCs were separated by using Can Patrol CTC enrichment technique. CTCs were divided into epithelial, mesenchymal and mixed phenotype based on different surface biomarkers. RNA in situ hybridization assay was used to detect the expression of Beclin1 gene. RESULTS: The percentages of epithelial, mesenchymal and mixed CTCs were 11.64%, 28.04% and 60.32%, respectively. There were no significant differences of initial CTCs counts between metastasis-free group (8.43 ± 5.15) and metastatic group (7.71 ± 3.82) (P > 0.05). As for metastatic group, the number of mixed CTCs at 12 months postoperatively was significantly higher than that of mixed CTCs preoperatively and 6 months postoperatively (P < 0.05). In the metastatic group, the number of Beclin1 positive CTCs was significantly higher than that of Beclin1 negative CTCs preoperatively (P < 0.05), moreover, there were several significantly changes of Beclin1 positive CTCs with different types and at different time points. CONCLUSION: The recurrence or metastasis of RCC was uncorrelated with initial CTCs counts, but probably related with the variation trend of CTCs, especially mesenchymal CTCs and Beclin1 positive CTCs.

EZH2 enhances the invasive capability of renal cell carcinoma cells via activation of STAT3.

The enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) gene has been recognized to be a proto­oncogene and to be linked to human malignancies. However, the additional functions of EZH2 in renal cell carcinoma (RCC) are not completely understood. In the present study, a possible role of EZH2 in RCC was identified. EZH2 was demonstrated to promote the cell proliferation and invasion potential of 769­P cells, and inhibition of EZH2 was demonstrated to prevent these two processes in 786­O cells. Mechanically, EZH2 was demonstrated to increase the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and upregulate 72 kDa type IV collagenase (MMP­2) expression. When cells were treated with small interfering RNA targeting STAT3 or Stattic, a specific inhibitor of STAT3, the invasive ability of the cells was decreased and downregulation of MMP­2 was observed. Based on these results, in the present study it was hypothesized that EZH2 may serve a critical role in the progression of RCC. Its ability to facilitate invasion makes EZH2 a promising target for the management of advanced RCC.

[Establishment of a method for in vitro culture of fetal rat testis tissue].

OBJECTIVE: To establish a method for in vitro culture of the fetal rat testis tissue. METHODS: Nine sexually mature specific-pathogen-free rats, 3 males and 6 females, weighing 200－250 g, were used for this study. The estrus of the female rats was determined according to the results of the vaginal smear test. The female rats were mated with the male ones in proestrus and estrus at night in the ratio of 2∶1 and observed the following day for conception (0.5 day post-conception ［dpc］) based on the presence of sperm in the vaginal smear. At 15.5 dpc, the fetal testes were isolated under the anatomical microscope, some for HE staining and the rest divided into a control and an hCG group to be cultured in a soft agar culture system at 37 ℃ in a humidified atmosphere containing 5% CO2. From the first day of culture (d 0), the development of the testes was observed under the inverted microscope, the culture medium collected and replaced on d 1, d 2, d 3 and d 4, and the testis tissue obtained on d 4. The concentration of testosterone in the culture medium was determined and the testis tissues were fixed, dehydrated and embedded for histological examination. RESULTS: Fetal rats were successfully obtained with the vaginal smear at 15.5 dpc, and the fetal testes effectively isolated, which were well developed, with gradual increase of their volume and enlargement of convoluted seminiferous tubules under the inverted microscope. Testosterone was observed in the culture medium, its concentration gradually increasing and reaching the peak on d 3, and its secretion stimulated by hCG. At 15.5 dpc. The fetal testes showed a histomorphological integrity, with typical seminiferous tubules, gonocytes, Sertoli cells and Leydig cells, but no central necrosis. Transmission electron microscopy revealed gonocytes and Sertoli cells within and Leydig cells between the seminiferous tubules, without obvious swelling of the mitochondria and endoplasmic reticula in the cells. CONCLUSIONS: The fetal rat testis tissue cultured in the soft agar culture system can develop well, retain its normal activity, and excrete testosterone into the culture medium.

Uniportal video-assisted thoracoscopic combined segmentectomy for lung cancer with incomplete fissure.

This video clip demonstrated a performance of uniportal video-assisted thoracoscopic surgery combined segmentectomy. The patient had a potential invasive nodule located near the bifurcation of right bronchus, 3-dimensional reconstruction image showed the fissure between posterior segment of upper lobe and superior segment of lower lobe was incomplete. An up-to-down approach was applied in this operation with the en bloc resection of the two segments. Pathological report was adenocarcinoma with negative margin (TNM stage: T1aN0M0).

Primary tracheal schwannoma treated by surgical resection: a case report.

The rarity and non-specific symptoms of benign primary tracheal tumors always leaded to misdiagnosis and delayed treatment, and also undefined the optimal treatment. In this case, a 45-year-old woman had a history of progressive shortness of breath and dry cough for several years, CT scan revealed an intra-luminal tracheal mass invaded the left side of tracheal wall. After being located by bronchoscope preoperatively, the tumor was removed by surgical resection. The tumor was 1.5 cm in diameter with intact capsule. The pathological result confirmed the diagnosis of schwannoma.

Silencing of Armadillo Repeat-Containing Protein 8 (ARMc8) Inhibits TGF-ß-Induced EMT in Bladder Carcinoma UMUC3 Cells.

Armadillo repeat-containing protein 8 (ARMc8) is a key factor in regulating cell migration, proliferation, tissue maintenance, and tumorigenesis. However, its role in bladder cancer remains unknown. Thus, in this study we sought to investigate the effect of ARMc8 on the epithelial-to-mesenchymal transition (EMT) progress in bladder cancer cells induced by transforming growth factor-ß1 (TGF-ß1). Our results found that ARMc8 was highly expressed in bladder cancer cell lines. ARMc8 silencing inhibited the TGF-ß1-induced migration and invasion and suppressed the EMT progress in bladder cancer cells. Furthermore, ARMc8 silencing inhibited the TGF-ß1-induced expression of ß-catenin, cyclin D1, and c-myc in bladder cancer cells. In conclusion, the present study demonstrates a novel function for ARMc8, which acts as a mediator for TGF-ß1-induced cell migration/invasion through modulation of the Wnt/ß-catenin signaling pathway in bladder cancer cells. This study suggests that ARMc8 may be a potential therapeutic target for the development of therapies for bladder cancer.