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Background: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC., Patients and Methods: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety., Results: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group., Conclusion: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975., (Copyright © 2023 X. Yan, M. Ye, Q. Zou, P. Chen, Z. He, B. Wu, D. He, C. He, X. Xue, Z. Ji, H. Chen, S. Zhang, Y. Liu, X. Zhang, C. Fu, D. Xu, M. Qiu, J. Lv, J. Huang, X. Ren, Y. Cheng, W. Qin, X. Zhang, F. Zhou, L. Ma, J. Guo, D. Ding, S. Wei, Y. He, H. Guo, B. Shi, L. Liu, F. Liu, Z. Hu, X. Jin, L. Yang, S. Zhu, J. Liu, Y. Huang, T. Xu, B. Liu, T. Sun, Z. Wang, H. Jiang, D. Yu, A. Zhou, J. Jiang, G. Luan, C. Jin, J. Xu, J. Hu, Y. H, Jun, W. Zhai, X. Sheng, Shanghai Junshi Biosciences Co. LTD, Shanghai Junshi Biosciences Co. LTD., a. Published by Elsevier Ltd.. All rights reserved.)

Non-muscle invasive bladder cancer (NMIBC) is a major type of bladder cancer with a high incidence worldwide, resulting in a great disease burden. Treatment and surveillance are the most important part of NIMBC management. In 2018, we issued "Treatment and surveillance for non-muscle-invasive bladder cancer in China: an evidence-based clinical practice guideline". Since then, various studies on the treatment and surveillance of NMIBC have been published. There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China. Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated. We formed a working group of clinical experts and methodologists. Through questionnaire investigation of clinicians including primary medical institutions, 24 clinically concerned issues, involving transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and intravesical immunotherapy of NMIBC, and follow-up and surveillance of the NMIBC patients, were determined for this guideline. Researches and recommendations on the management of NMIBC in databases, guideline development professional societies and monographs were referred to, and the European Association of Urology was used to assess the certainty of generated recommendations. Finally, we issued 29 statements, among which 22 were strong recommendations, and 7 were weak recommendations. These recommendations cover the topics of TURBT, postoperative chemotherapy after TURBT, Bacillus Calmette-Guérin (BCG) immunotherapy after TURBT, combination treatment of BCG and chemotherapy after TURBT, treatment of carcinoma in situ, radical cystectomy, treatment of NMIBC recurrence, and follow-up and surveillance. We hope these recommendations can help promote the treatment and surveillance of NMIBC in China, especially for the primary medical institutions., (© 2022. The Author(s).)

Background and Aim: Osteoporotic vertebral compression fractures (OVCFs) are acknowledged to be common fractures, especially in the elderly population. Minimally invasive percutaneous methods of treatment for these fractures such as kyphoplasty (KP) and vertebroplasty (VP) have been valid and effective tools for decreasing clinical problems, which are associated with more beneficial effects compared with traditional methods such as open surgery or conservative treatment. Hence, we conducted the current meta-analysis in order to gather updated evidence for the systematic assessment of clinical and radiographic outcomes of KP compared with VP., Methods: We searched articles published based on the electronic databases, including PubMed, EMBASE, and Cochrane Library. Publications of studies comparing KP with VP in the treatment of OVCFs were collected. After rigorous and thorough review of study quality, we extracted the data on the basis of eligible trials, which analyzed the summary hazard ratios (HRs) of the end points of interest., Results: Our inclusion criteria involved a total of 6 studies. In total, data from 644 patients, 330 who received VP and 284 who received KP, were included in the review. There was no significant difference in either group in terms of visual analog scale (VAS) scores (MD = 0.17; 95% CI, -0.39 to 0.73; P = .56), risk of cement leakage (odds ratio [OR] = 1.31; 95% CI, 0.62 to 2.74; P = .47) or Oswestry Disability Index (ODI) scores (MD = 0.51; 95% CI, -1.87 to 2.88; P = .68). Nevertheless, the injected cement volume (MD = -0.52; 95% CI, -0.88 to -0.15; P = .005) in the VP group was linked to a markedly lower statistically significant trend compared with the KP group., Conclusion: This meta-analysis evaluated acceptable efficacy levels across the involved trials. VP injected cement volume had several advantages in this meta-analysis. Yet, no significant differences were observed in terms of VAS scores, ODI scores, or cement leakage when KP was compared to VP therapy. Given the combined results of our study, the optimal treatment for patients with OVCFs should be determined by further high-quality multicenter randomized controlled trials with longer follow-up and larger sample sizes.

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline "2018 Standard Edition". However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons' surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons' skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH., (© 2022. The Author(s).)

Objectives: This study aimed to examine the efficacy and safety of acupoint catgut embedding (ACE) for obesity over a 16-week treatment period using sham stimulation as the control., Methods: A multicenter, randomised, parallel, sham-controlled trial was conducted from February 10, 2017, to May 15, 2018. Men with waistlines ≥85 cm and women with ≥80 cm at three sites were randomised to receive eight sessions (over 16 weeks) of ACE ( n  = 108) or sham ACE ( n  = 108) with skin penetration at sham acupoints. The catgut was embedded once every two weeks using two alternating sets of acupoints. The follow-up lasted for an additional 24 weeks. The primary outcome was the percentage waistline reduction from baseline to week 16., Results: We included 216 individuals in the intention-to-treat analysis. At 16 weeks, the rate of waistline reduction was 8.80% (95% confidence interval (CI), 7.93% to 9.66%) in the ACE group and 4.09% (95% CI, 3.18% to 5.00%) in the sham control group, with a between-group difference of 4.71% (95% CI, 3.47% to 5.95%; P  < 0.0001). This difference persisted throughout the entire follow-up period (between-group difference after 24-week additional weeks, 4.94% (95% CI, 3.58% to 6.30%); P  < 0.001). The subgroup analyses of waistline by sex (male/female) revealed treatment effects of 1.93 (95% CI, -0.37 to 4.23, P  = 0.1) in the male group and 3.19 (95% CI, 1.99 to 4.39, P  < 0.001) in the female group. The adverse event analysis suggested that ACE and laboratory tests confirmed the safety of ACE. Discussion . ACE for 16 weeks could decrease the waistline and weight and was safe for the treatment of obesity. Further research is needed to evaluate the long-term efficacy and sex differences. This trial is registered with NCT02936973., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Xia Chen et al.)

Background: Catgut implantation at acupoints (CIA) is a subtype of acupuncture that has been widely used to treat simple obesity, but evidence for its effectiveness remains scarce. The aim of this study is to evaluate the efficacy and safety of treating simple obesity with CIA., Objective: This clinical trial aims to evaluate the effectiveness and safety of CIA used for treatment of simple obesity., Methods: This is a multicentre, randomized, parallel, sham-controlled clinical trial. A total of 216 patients with simple obesity will be recruited. They will be randomly assigned in a 1:1 ratio to either the CIA group or the sham control group. All treatments will be given once every 2 weeks. The primary outcome measure is the rate of waistline reduction. Secondary outcome measures are the rates of reduction of body measurements, including weight, body mass index (BMI), hipline, waist-hip-ratio (WHR) and body fat percentage (BFP), the changes in scores on scales, including the Impact of Weight on Quality of Life Questionnaire (IWQOL-Lite), Short Form 36 (SF-36), the Hospital Anxiety and Depression Scale (HAD) and the Self-Esteem Scale (SES), Outcomes will be evaluated at baseline and at weeks 4, 8, 12, 16, 28, and 40, respectively. All adverse events that occur during this study will be recorded. If any participant withdraws from the trial, an intention-to-treat analysis (ITT) will be performed., Conclusion: This is a randomized, sham-controlled trial of CIA treatment for simple obesity. The results of this trial will provide more evidence on whether CIA is efficacious and safe for treating obesity., Trial Registration: ClinicalTrials.gov Identifier: NCT02936973. Registered on October 18, 2016.

Objective: To establish and promote the non-contact doctor-patient interactive diagnosis and treatment mode based on mobile internet for the treatment of coronavirus disease 2019 (COVID-19) with moxibustion therapy, and to observe the feasibility and effectiveness of the model in the pandemic., Methods: A total of 43 first-line medical staff and 149 suspected and confirmed cases with COVID-19 [18 cases in medical observation period, 17 cases of mild type (cold dampness and stagnation in the lung), 24 cases of ordinary type (cold-dampness accumulated in the lung) and 90 cases in recovery period ( qi deficiency of spleen and lung)] were included. A non-contact doctor-patient interactive diagnosis and treatment platform was established for the treatment of COVID-19 with indirect moxibustion plaster based on mobile internet. By the platform, the patients were instructed to use indirect moxibustion plaster in treatment. For the first-line medical staff and patients in the medical observation period, Zusanli (ST 36), Qihai (CV 6) and Zhongwan (CV 12) were selected. For the mild cases (cold dampness and stagnation in the lung) and the cases of ordinary type (cold-dampness accumulated in the lung), Hegu (LI 4), Taichong (LR 3), Zusanli (ST 36) and Guanyuan (CV 4) were selected. In the recovery period ( qi deficiency of spleen and lung), Dazhui (GV 14), Feishu (BL 13), Geshu (BL 17), Zusanli (ST 36) and Kongzui (LU 6) were used. The treatment was given once daily for 40 min each time. The intervention lasted for 10 days. After intervention, the infection rate and the improvement in the symptoms and psychological status of COVID-19 were observed in clinical first-line medical staff and COVID-19 patients., Results: In 10 days of intervention with indirect moxibustion plaster, there was "zero" infection among medical staff. Of 43 first-line physicians and nurses, 33 cases had some physical symptoms and psychological discomforts, mainly as low back pain, poor sleep and anxiety. After treatment, regarding the improvements in the symptoms and psychological discomforts, the effective rate was 78.8% (26/33) and the curative rate was 36.4% (12/33). Regarding the improvements in psychological discomforts, the effective rate was 58.3% (14/24) and the curative rate was 37.5 (9/24). Of 149 patients, 133 cases had the symptoms and psychological discomforts. After treatment, regarding the improvements in the symptoms and psychological discomforts, the effective rate was 81.2% (108/133) and the curative rate was 34.6% (46/133). Regarding the improvements in psychological discomforts, the effective rate was 76.5% (52/68) and the curative rate was 57.4 % (39/68)., Conclusion: It is feasible to apply the indirect moxibustion plaster technique based on mobile internet to the treatment COVID-19. This mode not only relieves the symptoms such as cough and fatigue, improves psychological state, but also possibly prevents the first-line medical staff from COVID-19.

[This corrects the article DOI: 10.1371/journal.pone.0164729.].

Microvesicles (MVs) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs-MVs) and miR-21 were demonstrated to ameliorate renal ischemia-reperfusion injury (IRI). Since hUC-MSC-MVs contained a substantial quantity of miR-21, we speculated that miR-21 might account for a part of the therapeutic effects of hUC-MSCs-MVs. The human tubule epithelial (HK-2) cells were cultured under low oxygen (LO) condition to mimic a cellular IRI model. A rat model of unilateral renal IRI was established. A co-culture model of HK-2 cells and MSC-MVs was utilized to examine the therapeutic role of MSC-MVs in HK-2 cell apoptosis and mechanism. The results showed that hUC-MSCs-MVs inhibited LO-induced HK-2 cell apoptosis through transferring miR-21 to HK-2 cells. Mechanistically, miR-21 directly targeted and negatively regulated programmed cell death protein 4 (PDCD4) in HK-2 cells. Moreover, PDCD4 overexpression in HK-2 cells abrogated the hUC-MSCs-MVs-inhibited HK-2 cell apoptosis under LO condition. Additionally, the beneficial effect of MSC-MVs on rat renal IRI was partly eliminated when miR-21 was knocked down in MSCs. Taken together, MSC-MVs inhibit tubular epithelial cell apoptosis and ameliorate renal IRI, at least partially, via delivery of miR-21.

Lingshu: Weiqixing (the Chapter 76 of Miraculous Pivot ) states the running course and time of the defensive qi circulation, as well as the needling techniques of acupuncture for waiting for qi arrival. However, because of the conflicts on the time system of acupuncture in the record, it is hard to be adopted in clinical practice in the later generations. In comparison of the 28-lunar-mansion time system with the clepsydra time system, it is known that the 28-lunar-mansion time system is much more rational because the clepsydra system is the tool for counting rather than timing. Hence, in compliance with the original meaning recorded in Lingshu: Weiqixing , the method for estimating the circulation of defensive qi is re-collected so as to provide a new approach to the study on the needling techniques of acupuncture for waiting for qi arrival.

Objectives: Microvesicles (MVs) derived from human Wharton's jelly mesenchymal stem cells (MSC-MVs) were demonstrated to ameliorate acute lung injury (ALI). We have previously found that MSC-MV-transferred hepatocyte growth factor was partly involved in their therapeutic effects. Since MSC-MVs also contained a substantial quantity of miR-100, which plays an important role in lung cancer and injury, we speculated that miR-100 might similarly account for a part of the therapeutic effects of MSC-MVs., Methods: MSCs were transfected with miR-100 inhibitor to downregulate miR-100 in MSC-MVs. A rat model of ALI and cell injury in rat type II alveolar epithelial cell line (L2) was induced by bleomycin (BLM). A co-culture model of alveolar epithelial cells and MSC-MVs was utilized to examine the therapeutic role of MSC-MVs and mechanism., Results: MSC-MV treatment attenuated BLM-induced apoptosis and inflammation in BLM-treated L2 cells and ameliorated BLM-induced lung apoptosis, inflammation, and fibrosis in BLM-induced ALI rats. The beneficial effect of MSC-MVs was partly eliminated when miR-100 was knocked down in MSCs. Moreover, MSC-MV-transferred miR-100 mediated the therapeutic effect of MSC-MVs in ALI through enhancing autophagy by targeting mTOR., Conclusion: MSC-MVs enhance autophagy and ameliorate ALI partially via delivery of miR-100.

Simple obesity is a worldwide epidemic associated with rapidly growing morbidity and mortality which imposes an enormous burden on individual and public health. As a part of Traditional Chinese Medicine (TCM), acupuncture has shown the positive efficacy in the management of simple obesity. In this article, we comprehensively review the clinical and animal studies that demonstrated the potential mechanisms of acupuncture treatment for simple obesity. Clinical studies suggested that acupuncture regulates endocrine system, promotes digestion, attenuates oxidative stress, and modulates relevant molecules of metabolism in patients of simple obesity. Evidence from laboratory indicated that acupuncture regulates lipid metabolism, modulates inflammatory responses, and promotes white adipose tissue browning. Acupuncture also suppresses appetite through regulating appetite regulatory hormones and the downstream signaling pathway. The evidence from clinical and animal studies indicates that acupuncture induces multifaceted regulation through complex mechanisms and moreover a single factor may not be enough to explain the beneficial effects against simple obesity.

In this report, protein of hairtail ( Trichiurus japonicas ) muscle was separately hydrolyzed using five kinds of proteases (alcalase, trypsin, neutrase, pepsin, and papain), and the papain- and alcalase-hydrolysates showed higher 2,2-diphenyl-1-picrylhydrazyl radicals (DPPH•) and hydroxyl radical (HO•) scavenging activity than other three protease hydrolysates. Therefore, the protein hydrolysate of hairtail muscle (HTP) was prepared using binary-enzymes hydrolysis process (papain + alcalase). Subsequently, eight antioxidant peptides were purified from HTP using membrane ultrafiltration and chromatography technology, and their amino acid sequences were identified as Gln-Asn-Asp-Glu-Arg (TJP1), Lys-Ser (TJP2), Lys-Ala (TJP3), Ala-Lys-Gly (TJP4), Thr-Lys-Ala (TJP5), Val-Lys (TJP6), Met-Lys (TJP7), and Ile-Tyr-Gly (TJP8) with molecular weights of 660.3, 233.0, 217.1, 274.1, 318.0, 245.1, 277.0, and 351.0 Da, respectively. TJP3, TJP4, and TJP8 exhibited strong scavenging activities on DPPH• (EC 50 0.902, 0.626, and 0.663 mg/mL, respectively), HO• (EC 50 1.740, 2.378, and 2.498 mg/mL, respectively), superoxide anion radical (EC 50 2.082, 2.538, and 1.355 mg/mL, respectively), and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical (EC 50 1.652, 0.831, and 0.586 mg/mL, respectively). Moreover, TJP3, TJP4, and TJP8 showed higher reducing power and inhibiting ability on lipid peroxidation in a linoleic acid model system. These results suggested that eight isolated peptides (TJP1 to TJP8), especially TJP3, TJP4, and TJP8 might serve as potential antioxidants applied in the pharmaceutical and health food industries.

Background: Hemangiopericytoma (HPC) is an uncommon soft tissue tumor arising from pericytes. The urogenital system is rarely affected., Methods: The review of the literature used the PubMed database which was searched up to March 2015., Results: Herein, we report the first case of lipomatous HPC of the corpus spongiosum in a 37-year-old man in China. The lesion presented as a quickly growing mass. Contrast enhanced CT showed a heterogeneous fatty mass with a multifocal enhancing soft-tissue component. Microscopically, the neoplasm was composed of spindle cells, a mature fat component and collagenous stroma. The mitotic index was low at 1 to 3 mitoses per 10 high-power fields. Immunohistochemically, STAT6, Bcl-2, CD99 and CDK4 were positive; CD34 and SMA were negative. The mature adipocytes were positive for S-100. Ki-67 expression was found in approximately 5% of the tumor cells. Surprisingly, there was a diffuse and strong nuclear expression of MDM2, but, no amplification of MDM2 was demonstrated by FISH. An adequate excision of the tumor was performed., Conclusion: No local recurrence or distant metastases occurred during the 18-month follow-up. In view of the unpredictable biological behavior of this tumor, a long follow-up period is mandatory., Competing Interests: None., (IJCEP Copyright © 2019.)

Objective: To explore the clinicopathological characteristics, diagnosis and treatment of penile verrucous carcinoma (VC)., Methods: We retrospectively analyzed the clinical data about 18 penile VC patients at the mean age of 52 (35－66) years. The tumors were cauliflower-like, measuring 2.5－8.7 cm in diameter, all with mucopurulentive discharge. A giant tumor invaded the perineum in 1 case, which had a history of surgical excision of penile condyloma acuminatum. The lesions invaded the glans penis in 2 cases, the shafts in 4 (all with a history of phimosis or redundant prepuce), and the whole penis in 11. Partial penectomy was performed for 2 cases with the proximal coronary sulcus involved and another 2 with the condylomata located in the glans penis and measuring <3.5 cm in diameter. Radical surgery was done for 2 cases of glans VC >3.5 cm in diameter, 11 cases with the whole penis involved, and 1 case with the perineum invaded., Results: Postoperative pathology showed well-differentiated tumor cells, negative surgical margins, papillary epithelia with hyperkeratosis and hyperplasia, and lymphocyte infiltration in the surrounding interstitial tissue in all the cases. Neither recurrence nor metastasis was found during the 1 to 8 years of follow-up., Conclusions: Penile VC is a special type of squamous cell carcinoma with little invasiveness and rare regional lymph node or distant metastasis, for the treatment of which partial penectomy or radical surgery confers good prognosis.

The use of radiotherapy in patients with clear cell renal carcinoma (ccRCC) is predominantly limited to palliation of metastases or control of local growth, because ccRCC cells readily develop radioresistance. The mechanisms underlying ccRCC resistance remain elusive. The present study demonstrated that ccRCC cells that survive fractionated radiation treatment display tumor-initiating cell (TIC) characteristics, such as high self-renewal and tumorigenic capacities, and overexpress stemness genes. ccRCC cells that survived fractionated radiation exhibited increased activation of the DNA damage checkpoint response and G2/M phase arrest compared with sham-irradiated cells. The results of the present study suggest that ionizing radiation destroys the bulk of tumor cells within ccRCC, but spares TICs; this subpopulation confers ccRCC radioresistance and may cause tumor recurrence or relapse following radiotherapy. Furthermore, these findings indicate that the DNA damage checkpoint response may serve as a potential therapeutic target for overcoming resistance of TICs in patients with ccRCC.

The elucidation of the underlying molecular mechanisms regulating the osteogenic differentiation of bone marrow‑derived mesenchymal stem cells (BMSCs) is of great importance in improving the treatment of bone‑associated diseases. MicroRNAs (miRNAs) have been proven to regulate the osteogenic differentiation of BMSCs. The present study investigated the role of miR‑217 in the osteogenic differentiation of rat BMSCs. It was observed that miR‑217 expression levels were downregulated during the process of osteogenic differentiation. Subsequently, a dual‑luciferase reporter gene assay demonstrated that miR‑217 targets a putative binding site in the 3'‑untranslated region of the runt related transcription factor 2 (Runx2) gene, which is a key transcription factor for osteogenesis. It was then demonstrated that overexpression of miR‑217 attenuated the osteogenesis of BMSCs and downregulated the expression of Runx2, whereas inhibition of miR‑217 promoted osteoblastic differentiation and upregulated Runx2 expression. Furthermore, the extracellular signal‑regulated kinase (ERK) and p38 mitogen‑activated protein kinase (p38 MAPK) signaling pathways were investigated during osteogenic induction, and the data indicated that miR‑217 may exert a negative effect on the osteogenic differentiation of BMSCs through alteration of ERK and p38 MAPK phosphorylation. The present study therefore concluded that miR‑217 functions as a negative regulator of BMSC osteogenic differentiation via the inhibition of Runx2 expression, and the underlying molecular mechanisms may partially be attributed to mediation by the ERK and p38 MAPK signaling pathways.

Objective: To evaluate the clinical effect of embedding sutures of single inner- and outer-prepuce flap in the treatment of concealed penis., Methods: This retrospective analysis included 37 cases of concealed penis treated by embedding sutures of single inner- and outer-prepuce flap between July 2011 and May 2015. Catheters were pulled out from the patients within 24 hours and the dressing removed about 1 week after surgery. All the patients were followed up for 12－24 months postoperatively for evaluation of the long-term outcomes of surgery., Results: One-stage wound healing was achieved in all the patients. No foreskin flap necrosis, inflammation, edema, voiding dysfunction, or painful erection was found during the follow-up. The penises were extended by 2－4 cm. No complications were observed axcept 8 cases of mild prepuce edema, which all subsided with 6 months postoperatively., Conclusions: Embedding sutures of single inner- and outer-prepuce flap, with the advantages of simple operation, rapid recovery and few complications, is a desirable surgical option for the treatment of concealed penis.

Hyphantria cunea (Drury) (Lepidoptera: Arctiidae) is an invasive insect pest which, in China, causes unprecedented damage and economic losses due to its extreme fecundity and wide host range, including forest and shade trees, and even crops. Compared to the better known lepidopteran species which use Type-I pheromones, little is known at the molecular level about the olfactory mechanisms of host location and mate choice in H. cunea, a species using Type-II lepidopteran pheromones. In the present study, the H. cunea antennal transcriptome was constructed by Illumina Hiseq 2500TM sequencing, with the aim of discovering olfaction-related genes. We obtained 64,020,776 clean reads, and 59,243 unigenes from the analysis of the transcriptome, and the putative gene functions were annotated using gene ontology (GO) annotation. We further identified 124 putative chemosensory unigenes based on homology searches and phylogenetic analysis, including 30 odorant binding proteins (OBPs), 17 chemosensory proteins (CSPs), 52 odorant receptors (ORs), 14 ionotropic receptors (IRs), nine gustatory receptors (GRs) and two sensory neuron membrane proteins (SNMPs). We also found many conserved motif patterns of OBPs and CSPs using a MEME system. Moreover, we systematically analyzed expression patterns of OBPs and CSPs based on reverse transcription PCR and quantitative real time PCR (RT-qPCR) with RNA extracted from different tissues and life stages of both sexes in H. cunea. The antennae-biased expression may provide a deeper further understanding of olfactory processing in H. cunea. The first ever identification of olfactory genes in H. cunea may provide new leads for control of this major pest., Competing Interests: The authors have declared that no competing interests exist.

Objective: The aim of this study was to evaluate the effects of grape seed procyanidin extract (GSPE) on cell proliferation and apoptosis in human bladder cancer BIU87 cells and to investigate its molecular mechanism in vitro., Materials and Methods: BIU87 cells were treated with different concentrations of GSPE for 24h in vitro while an untreated group was taken as control. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, Hoechst 33258 staining, flow cytometry, RT-PCR and Western blot were used to detect the anti-proliferation and apoptotic induction effects of GSPE on BIU87 cells., Results: It was found that GSPE inhibited the cell growth through cell cycle arrest at G1 phase and induced cell apoptosis in BIU87 cells in a dose-dependent manner. Semi-quantitated RT-PCR and Western blot analyses indicated that GSPE increased caspase-3 (p<0.01), but decreased the expression of cyclinD1, CDK4 and survivin (p<0.01)., Conclusions: GSPE inhibits cell proliferation by inducing cell cycle arrest and apoptosis in BIU87 cells, and the effect may be related with its down-regulation of cyclinD1, CDK4 and survivin.

Objective: To investigate the clinical application value of 8.5/11.5 F transurethral seminal vesiculoscopy in the diagnosis and treatment of refractory hematospermia., Methods: We retrospectively analyzed 78 cases of refractory hematospermia diagnosed and treated by 8.5/11.5 F transurethral seminal vesiculoscopy from June 2012 to June 2014. The patients underwent serum PSA examination, transrectal ultrasonography, seminal vesicle ultrasonography, and pelvis CT or MRI before surgery, and all received transurethral seminal vesiculoscopy under the 8.5/11.5 F rigid ureteroscope., Results: Operations were all successfully accomplished, which revealed abnormal opening of the ejaculatory duct in 5 cases, mucosal inflammatory hyperemia in the prostatic utricle and seminal vesicle in 78, dark red mucilage substance in the seminal vesicle in 34, seminal vesicle stones in 19, small polyp in the seminal vesicle in 2, and ejaculatory duct or seminal vesicle cyst in 4. All the patients received symptomatic treatment during the surgery. After surgery, hematouria was found in 13 cases, which disappeared within 2 weeks, pelvic hematoma in 1 case, which was cured by conservative treatment within 3 months, and epididymitis in 2 cases, which was controlled by anti-infection treatment. Hematospermia recurred in 3 cases during the 1-year postoperative follow-up., Conclusion: 8.5/11.5 F transurethral seminal vesiculoscopy, with its advantages of easy operation, wide field of vision, large channel for operation, and few complications, deserves general clinical application in the diagnosis and treatment of refractory hematospermia.

Objectives: To explore the expression of aquaporin 1 (AQP1) in bladder uroepithelium cell carcinoma (BUCC) and its relevance to recurrence., Materials and Methods: Tissue samples from 45 BUCC patients who underwent total cystectomy or transurethral resection of bladder tumor (TURBT) and from 40 patients with non-bladder cancers who underwent special detection or treatments were collected. The level of expression of AQP1 in BUCC tissues and normal bladder tissues was assessed by immunohistochemistry so as to analyze the relevance to pathological patterns and time of recurrence in BUCC patients., Results: The expression levels of AQP1 normal bladder tissues and BUCC tissues were 2.175±0.693 and 3.689±0.701, respectively, and the difference was significant (t=9.99, P<0.0001). Marked increase was noted with BUCC histological grade and pathological stage (P<0.01). Moreover, the expression of AQP1 was evidently higher in cancerous tissues with lymph node metastasis than in those without (P<0.01). With short-term recurrence, the positive cell expression rate of AQP1 was higher in primary tissues, which increased obviously after recurrence. Additionally, the recurrent time of BUCC was negatively associated with the positive cell expression rate of AQP1 and the difference between the expression of AQP1 before and after recurrence (r=-0.843, F=39.302, P=0.000; r=-0.829, F=35.191, P=0.000)., Conclusions: AQP1, which reflects the grade, stage, lymph node metastasis and recurrence of BUCC, has potential guiding significance in the diagnosis and treatment of bladder cancarcinoma.

Prostate cancer is a leading cause of death in male populations across the globe. With the advent of gene expression arrays, many microarray studies have been conducted in prostate cancer, but the results have varied across different studies. To better understand the genetic and biologic mechanisms of prostate cancer, we conducted a meta-analysis of two studies on prostate cancer. Eight key genes were identified to be differentially expressed with progression. After gene co-expression analysis based on data from the GEO database, we obtained a co- expressed gene list which included 725 genes. Gene Ontology analysis revealed that these genes are involved in actin filament-based processes, locomotion and cell morphogenesis. Further analysis of the gene list should provide important clues for developing new prognostic markers and therapeutic targets.

Background: Susceptibility weighted imaging (SWI) is a new MRI technique which has been proved very useful in the diagnosis of brain diseases, but few study was performed on its value in prostatic diseases. The aim of the present study was to investigate the value of SWI in distinguishing prostate cancer from benign prostatic hyperplasia and detecting prostatic calcification., Methodology/principal Findings: 23 patients with prostate cancer and 53 patients with benign prostatic hyperplasia proved by prostate biopsy were scanned on a 3.0T MR and a 16-row CT scanner. High-resolution SWI, conventional MRI and CT were performed on all patients. The MRI and CT findings, especially SWI, were analyzed and compared. The analyses revealed that 19 out of 23 patients with prostate cancer presented hemorrhage within tumor area on SWI. However, in 53 patients with benign prostatic hyperplasia, hemorrhage was detected only in 1 patient in prostate by SWI. When comparing SWI, conventional MRI and CT in detecting prostate cancer hemorrhage, out of the 19 patients with prostate cancer who had prostatic hemorrhage detected by SWI, the prostatic hemorrhage was detected in only 7 patients by using conventional MRI, and none was detected by CT. In addition, CT demonstrated calcifications in 22 patients which were all detected by SWI whereas only 3 were detected by conventional MRI. Compared to CT, SWI showed 100% in the diagnostic sensitivity, specificity, accuracy, positive predictive value(PPV) and negative predictive value(NPV) in detecting calcifications in prostate but conventional MRI demonstrated 13.6% in sensitivity, 100% in specificity, 75% in accuracy, 100% in PPV and 74% in NPV., Conclusions: More apparent prostate hemorrhages were detected on SWI than on conventional MRI or CT. SWI may provide valuable information for the differential diagnosis between prostate cancer and prostatic hyperplasia. Filtered phase images can identify prostatic calcifications as well as CT.

Objective: To improve the early diagnosis and therapeutic outcomes of testicular torsion., Methods: We retrospectively reviewed the clinical data of 49 cases of testicular torsion along with the results of their intratesticular color Doppler flow imaging (CDFI) and spermatic cord sonography., Results: Of the 49 cases, 42 showed abnormal intratesticular blood flow, including 3 cases of increased blood flow, while the other 7 presented no obvious abnormality. Morphological abnormality of the spermatic cord was found in 47 cases. Twenty-eight cases underwent testis removal, and the other 21 received detorsion and orchidopexy, in which 12 testes were preserved with normal size and blood flow., Conclusion: Spermatic cord sonography and intratesticular CDFI play an important role in the early diagnosis of testicular torsion. And early surgical exploration contributes to the preservation of the testis.

Objective: To investigate the synergistical killing effect of docetaxel combined with ABT-737 on human prostate cancer cell line PC-3 by inducing apoptosis and further to determine the mechanism underlying such effect., Methods: PC-3 cells were treated with various concentrations of docetaxel or (and) ABT-737. Cell viability was determined using MTT assay. Apoptosis was assessed by fluorescence microscopy analysis of cells with condensed and segmented nuclei following staining with 4',6-diamidino-2-phenylindole (DAPI). Cellular DNA was stained with propidium iodide and flow cytometric analysis was performed to analyze the cell cycle distribution. Bcl-2, Bax, Bcl-xL and Mcl-1 protein changes were detected by Western blot. The activity of caspase-3 was measured using a colorimetric assay., Results: Docetaxel (20 nmol/L) combination with ABT-737 (400 nmol/L) for 48 hours, the cell viability was decreased to 19.7% ± 3.2% to compare with 44.2% ± 4.4% (t = 4.45) of docetaxel and 93.2% ± 1.8% of ABT-737 separately and there was a synergistic effect between the two drugs (CI = 0.8). Apoptosis rate of the combination group was higher than other two drugs. Docetaxel increased the cell number arrested in G(2)/M phase compared with control group (P < 0.05), but the combination treatment resulted in a significant arrest in the G(0)/G(1) phase. The combination treatment could significantly reduced the Bcl-2, Bcl-xL and Mcl-1 expression (F = 369.53, 57.89 and 32.77, all P < 0.05) and enhanced the activity of caspase-3 (419.7% ± 15.6%) (F = 207.33, P < 0.05)., Conclusions: The combination of ABT-737 with docetaxel can synergistically inhibit the proliferation of PC-3 cells through inducing apoptosis, which may be associated with cell cycle arrest, down-regulation of Bcl-2, Bcl-xL and Mcl-1 expression and activation of caspase-3.

In the title compound, [Mn(C(8)H(6)N(5)O(4))(2)(H(2)O)(2)], the Mn(II) ion is situated on an inversion center and is six-coordinated by two N and two O atoms from two L ligands (HL = 2-[(1H-1,2,4-triazol-1-yl)meth-yl]-1H-imidazole-4,5-dicarboxylic acid) and two water mol-ecules in a distorted octa-hedral geometry. In ligand L, the imidazole and triazole rings form a dihedral angle of 74.25 (8)°. Mol-ecules are assembled into a three-dimensional structure via inter-molecular O-H⋯O, O-H⋯N and N-H⋯N hydrogen-bonds, and π-π inter-actions with a short distance of 3.665 (2) Å between the centroids of the imidazole and triazole rings of neighbouring mol-ecules.

By using molecular marker of group I intron, a field evaluation was made on the efficacy of sustainable control of Monochamus alternatus by non-woven fabric bands impregnated with Beauveria bassiana. The results showed that the control efficacy in two treated plots was 19.5% and 10.8%, and 14.2% and 11% when evaluated with conventional and molecular evaluation methods, respectively, suggesting that the conventional method which evaluated the control efficacy in terms of microbes mortality or infection rate couldn't distinguish the efficacies caused by released biocontrol agents and indigenous pathogens, while molecular method could avoid the interference of indigenous pathogens and give an objective and reasonable evaluation on the efficacy of microbial control.