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Purpose: Androgen deprivation therapy (ADT), including enzalutamide, induces resistance in prostate cancer; ADT resistance is associated with neuroendocrine differentiation (NED) and tumor-associated macrophages (TAM). This study aimed to investigate the association between enzalutamide-induced NED and TAMs and its mechanism.Experimental Design: The association between enzalutamide-induced NED and TAMs was investigated by IHC using prostate cancer tissues, enzalutamide-resistant mouse xenografts, and a coculture system. The underlying mechanisms were assessed using in vitro cytokine antibody arrays, ELISAs, chromatin immunoprecipitation, and other methods. An orthotopic prostate cancer mouse model was established to evaluate the in vivo effects of combined IL6 receptor (IL6R) and high mobility group box 1 (HMGB1) inhibition on enzalutamide resistance.Results: High CD163 expression was observed in ADT-treated prostate cancer or castration-resistant prostate cancer (CRPC) tissues with high levels of neuron-specific enolase (NSE) and chromogranin A (CHGA) and in enzalutamide-resistant xenografts, indicating the crucial roles of NED and TAMs in enzalutamide resistance. Specifically, enzalutamide-induced HMGB1 expression facilitated TAM recruitment and polarization and drove NED via β-catenin stabilization. HMGB1-activated TAMs secreted IL6 to augment enzalutamide-induced NED and directly promote HMGB1 transcription via STAT3. Finally, inhibition of the IL6/STAT3 pathway by tocilizumab combined with HMGB1 knockdown inhibited enzalutamide-induced resistance in an orthotopic prostate cancer mouse model.Conclusions: Enzalutamide elevates HMGB1 levels, which recruits and activates TAMs. Moreover, IL6 secreted by HMGB1-activated TAMs facilitates the enzalutamide-induced NED of prostate cancer, forming a positive feedback loop between NED in prostate cancer and TAMs. The combined inhibition of IL6R and HMGB1 may serve as a new treatment for enzalutamide resistance in patients with advanced or metastatic prostate cancer. Clin Cancer Res; 24(3); 708–23. ©2017 AACR.

Purpose: Cancer stem-like cells (CSC) contribute to the progression and androgen deprivation therapy (ADT) resistance of prostate cancer. As CSCs depend on their specific niche, including tumor-associated macrophages (TAM), elucidating the network between CSCs and TAMs may help to effectively inhibit the progression and ADT resistance of prostate cancer.Experimental Design: The underlying intracellular mechanism that sustains the stem-like characteristics of CSCs in prostate cancer was assessed via RNA sequencing, co-immunoprecipitation, chromatin immunoprecipitation, and other assays. A coculture system and cytokine antibody arrays were used to examine the interaction network between CSCs and TAMs. In addition, an orthotopic prostate cancer model was established to evaluate the in vivo effects of the combined targeting of CSCs and their interaction with TAMs on ADT resistance.Results: Autophagy-related gene 7 (ATG7) facilitated the transcription of OCT4 via β-catenin, which binds to the OCT4 promoter, promoting CSC characteristics in prostate cancer, including self-renewal, tumor initiation, and drug resistance. In addition, CSCs remodeled their specific niche by educating monocytes/macrophages toward TAMs, and the CSC-educated TAMs reciprocally promoted the stem-like properties of CSCs, progression and ADT resistance of prostate cancer via IL6/STAT3. Furthermore, the combined targeting of CSCs and their interaction with TAMs by inhibiting ATG7/OCT4 and IL6 receptor effectively ameliorated ADT resistance in an orthotopic prostate cancer model.Conclusions: Targeting CSCs and their niche may prove to be a more powerful strategy than targeting CSCs alone, providing a rational approach to ameliorating ADT resistance in prostate cancer. Clin Cancer Res; 24(18); 4612–26. ©2018 AACR.

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BACKGROUND Guillain-Barré syndrome (GBS) is a rare disorder that typically presents with ascending weakness, pain, paraesthesias, and numbness, which mimic the findings in lumbar spinal stenosis. Here, we report a case of severe lumbar spinal stenosis combined with GBS. CASE SUMMARY A 70-year-old man with a history of lumbar spinal stenosis presented to our emergency department with severe lower back pain and lower extremity numbness. Magnetic resonance imaging confirmed the diagnosis of severe lumbar spinal stenosis. However, his symptoms did not improve postoperatively and he developed dysphagia and upper extremity numbness. An electromyogram was performed. Based on his symptoms, physical examination, and electromyogram, he was diagnosed with GBS. After 5 d of intravenous immunoglobulin (0.4 g/kg/d for 5 d) therapy, he gained 4/5 of strength in his upper and lower extremities and denied paraesthesias. He had regained 5/5 of strength in his extremities when he was discharged and had no symptoms during follow-up. CONCLUSION GBS should be considered in the differential diagnosis of spinal disorder, even though magnetic resonance imaging shows severe lumbar spinal stenosis. This case highlights the importance of a careful diagnosis when a patient has a history of a disease and comes to the hospital with the same or similar symptoms.

BACKGROUND Empty sella syndrome is a condition in which the pituitary gland shrinks or flattens. Patients with empty sella syndrome often present with headache, hypertension, obesity, visual disturbances, cerebrospinal fluid (CSF) rhinorrhoea, or endocrine dysfunction. Herein, we report a rare case of empty sella syndrome discovered after the patient experienced postoperative hypotension and respiratory failure. CASE SUMMARY A 60-year-old man was admitted for further workup of left shoulder pain. He was assessed by the orthopaedics team and booked for internal fixation of the left clavicle. General anaesthesia with a nerve block was administered. His blood pressure continued to decrease post-operation. Endocrine tests were performed, with the results supporting a diagnosis of hypopituitarism with hypocortisolism and hypothyroidism. Brain magnetic resonance imaging demonstrated that the sella was enlarged and filled with CSF, confirming a diagnosis of empty sella syndrome. The patient was started on endocrine replacement therapy. The patient regained consciousness and spontaneous breath finally. CONCLUSION This case highlights the importance of considering pituitary hormone insufficiency in the context of respiratory and hemodynamic failure during the perioperative period.

Cryptococcus gattii (C. gattii) is a lethal pathogen that causes the majority of cryptococcosis cases in previously healthy individuals. This pathogen poses an increasing threat to global public health, but the mechanisms underlying the pathogenesis have remained to be fully elucidated. In the present study, the role of high-osmolarity glycerol (HOG)1 in the stress reaction and virulence control of C. gattii was characterized by deleting the HOG1 gene using the clinical isolate strain CZ2012, and finally, the virulence and pathogenic traits of the deletion strain were defined. Deletion of the HOG1 gene resulted in notable growth defects under stress conditions (high salt and antifungal drugs), but different traits were observed under oxidative stress conditions (hydrogen peroxide). Similarly, the C. gattii hog1Δ strains (deletion of HOG1) also displayed decreased capsule production and melanin synthesis. Furthermore, mice infected with the hog1Δ strain had longer survival times than those infected with the wild-type strain and the reconstituted strain. The hog1Δ strain recovered from infected organs exhibited significant growth defects in terms of decreased colony count and size. The present results suggested that HOG1 has a significant role in the virulence of C. gattii and these results may help to elucidate the pathogenesis of C. gattii.

Microbubbles magnify the acoustic pressure of low-intensity pulsed ultrasound (LIPUS) and may enhance its bioeffect for diagnostic and therapeutic purposes. This study compared the effect of this novel microbubble-mediated ultrasound (MUS) with that of the traditional LIPUS on osteogenesis and neovascularization in a rabbit model of steroid-associated osteonecrosis. We hypothesized that MUS might outweigh LIPUS on promoting osteogenesis and neovascularization in steroid-associated osteonecrosis. The bilateral femoral head necrosis was induced by lipopolysaccharide and methylprednisolone in the rabbits. The indices of bone mineral density (BMD), trabecular number, maximal loading strength, and mineral apposition rate were analyzed, demonstrating that the animal model of steroid-associated osteonecrosis was successfully established. Both the MUS group (GM) and the LIPUS group (GL) were insonated 20 min daily for six weeks. GM received an extra intracapsular injection of microbubbles before insonation every other day. Fluorescence bone labeling, Micro-CT Analysis, biomechanical test, quantitative real-time PCR, Western blot analysis, and histological evaluation were performed for comparing GM with GL. The results demonstrated a 39% higher mineral apposition rate in GM compared with GL. The BMD and the maximal loading strength of femoral head of GM increased by 4.3% and 27.8% compared to those of GL, respectively. The mRNA and protein expression of BMP-2 and VEGF were also significantly higher in GM. The number of blood vessels of GM was 65% greater than that of GL. MUS is more potent than LIPUS in enhancing osteogenesis, neovascularization, and biomechanical strength of femoral head in the animal model of steroid-associated osteonecrosis. Without increasing the intensity of insonation or the risk of tissue damage, MUS is better for inhibiting the process of steroid-associated osteonecrosis.

Background The objective of this study was to investigate the potency of platelet-rich plasma (PRP) combined with bone marrow mesenchymal stem cells (BMSCs) to promote tendon–bone healing in a rabbit model. Methods In the in vitro study, the effects of PRP on osteogenic induction of BMSCs were analysed. Later, PRP with or without BMSCs was used in the rabbit model of anterior cruciate ligament reconstruction. Specimens were harvested 8 weeks postoperatively to evaluate tendon–bone healing by histology, radiology, and biomechanical testing. Results The in vitro study revealed that collagen I, osteocalcin, and osteopontin expression was higher in BMSCs co-cultured with PRP for 14 days. The in vivo study revealed a more mature tendon–bone interface using light microscopy, a more newly formed bone at the bone tunnel walls detected by micro-computed tomography, and a significantly higher failure load as assessed by biomechanical testing in the BMSC + PRP group than in the control and PRP groups. Conclusions These results indicate that the combination of PRP and BMSCs promotes tendon–bone healing and has potential for clinical use. Electronic supplementary material The online version of this article (doi:10.1186/s13018-016-0433-7) contains supplementary material, which is available to authorized users.

To investigate the relationship of muscle mass and muscle function with age.The study including 415 participants (aged 60-99 years). Upper (UMM) and lower (LMM) limbs muscle mass and whole body fat free mass (FFM) were measured by bioelectrical impedance analysis. The appendicular skeletal muscle mass (ASM) index (ASM/height2) was calculated. Muscle function was assessed by measuring hand grip strength (HGS) and gait speed.Using ASM index cutoff values we found that higher prevalence of sarcopenia in women than in men (33.5% vs 23.6%, p=0.025). In the upper limb, HGS (β=-0.809) declined more rapidly with age than did UMM (β=-0.592) in men, but not in women (β=-0.389 and β=-0.486 respectively). In the lower limb, gait speed declined more rapidly than LMM in both men (β=-0.683 vs β=-0.442) and women (β=-1.00 vs β=-0.461). The variance of UMM explained 28-29% of the variance of HGS, and LMM explained 7-8% of the variance of gait speed in women and men respectively. In addition to the common predictors (BMI and age), the specific predictors were smoking, exercise and education for FFM and ASM, and smoking, drinking and exercise for HGS (p0.05).Loss of muscle function is greater than the decline of muscle mass particularly in the upper limbs in men. However, women are more prone to have low muscle mass than the men. Exercise programs need to be designed gender specifically.目的：探讨与年龄相关的骨骼肌肌量与功能之间的关系。方法：本研究包括 415 名年龄在6099 岁之间的受试者。采用人体成分仪测量上肢和下肢骨骼肌 肌量、去脂组织。四肢骨骼肌肌量指数=四肢骨骼肌肌量/身高平方。采用握力 与步速评价骨骼肌功能。结果：老年男性、女性骨骼肌肌量低于切点值的比 例分别是（ 23.6% vs 33.5% ， p=0.025 ） 。老年男性随年龄的增加握力 （β=0.809）下降快于上肢骨骼肌肌量（β=-0.592），但在老年女性中不存在 同样的情况（β=0.389 和β=0.486）。在老年男性（β=0.683 vs β=0.442） 与女性（β=1.00 vs β=0.461）中，步速下降快于下肢骨骼肌肌量。老年男性 与女性上肢骨骼肌肌量与握力的决定系数是2829%，下肢骨骼肌肌量与步速 的决定系数是（78%）。除体重指数与年龄外，吸烟、运动和受教育情况与 四肢骨骼肌肌量、去脂组织相关。吸烟、饮酒与握力呈负相关（p0.05）。结 论：老年男性上肢骨骼肌功能下降快于骨骼肌肌量。然而，老年女性骨骼肌 肌量低于切点值的百分比大于男性。运动方案的制定需要考虑性别的因素。.

Microvascular invasion (MVI), an omen of potential hematogenous spread of tumor cells, has been identified as an accepted risk factor for poor prognosis in some solid tumors. But its prognostic value in renal cell carcinoma (RCC) remains disputable. In order to address this question rigorously, we performed a systematical review of the published literature on MVI and RCC prognosis. According to the PRISMA statement, we searched PubMed, Web of science, and Cochrane Library database and identified 33 cohort articles that met the eligibility criteria and involved 14,946 patients (48-2596 per study) in this meta-analysis. Using the random effects model, the association between MVI and four generally recognized end points were estimated, including cancer-specific survival (CSS), recurrence-free survival (RFS), metastasis-free survival (MFS) and overall survival (OS). The presence of MVI was detected in 14.4% of the pathological specimens. A higher incidence of MVI was associated with some acknowledged prognostic risk factors such as higher pathological TNM stages and higher tumor grades. Statistical significance of the combined hazard ratio (HR) was detected for CSS (HR, 2.090; 95% CI, 1.530-2.857), RFS (HR = 2.749; 95% CI, 1.974-3.828), MFS (HR = 1.621; 95% CI, 1.095-2.400). However, the association between MVI and worse overall survival did not address statistical significance (HR = 1.371; 95% CI, 0.978-1.923). These findings suggest that the presence of MVI has a detrimental effect on clinicopathological features of RCC and could serve as a poor prognostic factor for patient with RCC.

To study the risk environmental and psycho-social factors associated to prostate cancer (PCa) in Chinese population.250 PCa patients and 500 controls were enrolled in this case-control study. Information was collected and logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI) for relationship between lifestyle, eating habits and psycho-social factors with PCa risk.Green vegetables and green tea were associated with a decreased risk of PCa (OR=0.39, 95% CI: 0.28-0.53; OR=0.59, 95% CI: 0.40-0.87, respectively). Family history of PCa (OR=7.16, 95% CI: 2.01-25.49), history of prostate diseases (OR=2.28, 95% CI: 1.53-3.41), alcohol consumption (OR=1.97, 95% CI: 1.33-2.90), red meat consumption (OR=1.74, 95% CI: 1.20-2.52), barbecued (OR=2.29, 95% CI: 1.11-4.73) or fried (OR=2.35, 95% CI: 1.24-4.43) foods were related with increased PCa risk. Negative psycho-social factors including occupational setbacks (OR=1.61, 95% CI: 1.00-2.59), marital separation (OR=1.94, 95% CI: 1.29-2.91), self-contained suffering (OR=2.37, 95% CI: 1.58-3.55), and high sensitivity to the personal comments (OR=1.73, 95% CI: 1.18-2.54) were related to PCa.Regular consumption of green vegetables and green tea may suggest protective effects on PCa. Alcohol consumption, red meat consumption and barbecued or fried foods were associated with PCa. Negative psycho-social factors may also play a role in the incidence of PCa in Chinese population.

Transurethral resection of the bladder tumor (TURBT) remains the gold standard for non-muscle-invasive bladder cancer (NMIBC). Laser techniques have been widely used in urology. This analysis aimed to assess the safety and efficacy of holmium resection of the bladder tumor (HoLRBT) vs. TURBT.A systemic search of MEDLINE, Embase, Web of Science, and The Cochrane Library as well as manual bibliography searches were performed to identify the relevant studies. The pooled estimates of operation time, obturator nerve reflex rate, bladder perforation rate, bladder irrigation rate, catheterization time, hospital stay, and one- and two-year recurrence free survivals were calculated.Five studies were enrolled into our meta-analysis. No significant difference was observed in the operation time between groups (weighted mean difference (WMD) 1.01, 95% confidential interval (95% CI) -3.52 - 5.54, P = 0.66). The significant difference in the obturator nerve reflex (OR 0.05, 95% CI 0.01 - 0.04, P = 0.004), bladder perforation (OR 0.14, 95% CI 0.03 - 0.61, P = 0.009), bladder irrigation (OR 0.13, 95% CI 0.04 - 0.45, P = 0.001), catheterization time (WMD -0.96, 95% CI -1.11 to -0.82, P0.00001), and hospital stay (WMD -1.46, 95% CI -1.65 to -1.27, P0.00001) showed advantages of HoLRBT over TURBT. The 2-year recurrence free survival rate favors the HoLRBT group (OR 1.46, 95% CI 1.02 - 2.11, P = 0.04).As a promising technique, HoLRBT is safe and efficient, and showed several advantages over TURBT. HoLRBT can be used as an alternative procedure for TURBT in terms of low-grade papillary urothelial carcinoma or low-grade early TNM-stage urothelial carcinoma.

Ectopic Cushing’s syndrome caused by pheochromocytoma is rare. We reported a 15-year-old female patient who was admitted to hospital with typical Cushing’s syndrome. She had not started menstruation. Her plasma adrenocorticotropic hormone (ACTH) and 24-hour urinary free cortisol levels were extremely high. Gonadal and progestational hormone levels were also abnormal. Abdominal computed tomography scans and enhanced scans revealed multiple irregular tumors in the right adrenal. Pelvic echogram showed an infantile uterus, while the ovaries were at an immature stage of development. Retroperitoneal laparoscopic right adrenalectomy was performed without intraoperative complications. Histology and immunohistochemistry of the tumor were consistent with pheochromocytoma. Retroperitoneal laparoscopic adrenalectomy is a safe procedure with satisfactory outcomes and allows for rapid recovery.

To summarize our preliminary clinical experiences of laparoendoscopic single-site (LESS) retroperitoneal adrenalectomy.Since October 2009 to January 2011, the investigators have performed LESS retroperitoneal adrenalectomy for 7 patients with adrenal tumors. A waist axillary midline incision of around 2 - 3 cm was made and a single incision for inserting a homemade port. Cambridge endo flexible laparoscopic instrument and other common laparoscopic accessories were used during the surgical procedures.LESS retroperitoneal adrenalectomies were technically successful in 6 cases with no extra skin incisions, no conversion into an open procedure or standard laparoscopy. Conversion to standard laparoscopy (3 ports) was inevitable in one case. The reason for conversion was due to tumor size (6 cm). No perioperative complication occurred. The mean operative duration was 139 min (95 - 200 min), the mean volume of blood loss 96 ml (30 - 350 ml) and the mean hospital stay 5 d (3 - 8 d).LESS retroperitoneal adrenalectomy is technically feasible and safe for the treatment of small adrenal tumors.

Laparoscopic radical prostatectomy is considered the first treatment of choice for local prostate cancer due to its minimal invasion advantage. To further achieve the goal of minimal invasion, single port laparoscopic radical prostatectomy has been developed to minimize the complications associated with puncture tracks. The aim of this study was to illustrate the technique for single port laparoscopic radical prostatectomy and evaluate its efficacy and safety. We reported 8 cases of radical prostatectomy with excellent early outcome carried out in Shanghai Changzheng Hospital from June 2009 to August 2009 using a home-made multiple instrument access port and adding an additional small incision at McBurney point.

To investigate the relationship between oxytocin (OT) and male infertility, serum OT baseline concentration and oxytocin receptor (OTR) gene expression in fertile and infertile men were investigated.Twenty obstructive azoospermia patients, twenty five idiopathic asthenozoospermia patients, twenty idiopathic oligozoospermia patients and twenty healthy subjects were taken into consideration. Serum OT baseline concentration was determined by radioimmunoassay. Moreover, serum concentration of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T) were determined by chemoluminescence to evaluate the correlation with OT. OTR gene promotor and OTR mRNA expressions were determined by polymerase chain reaction and reverse transcriptase-polymerase chain reaction, respectively. OTR protein expression was also performed by Western Blot.Serum OT baseline concentrations in infertile groups were significantly higher than in fertile group (F0.05/2(2,82) = 8.29, p 0.001). Serum baseline concentration of OT was not correlated with that of LH, FSH and T. There was no significant difference in gene sequences of OTR gene promotor and OTR mRNA when comparing infertile patients with fertile. Human OTR was in the form of oligomers and monomers, and the oligomers were in the majority containing tetramers and hexamers. Monomer expression was significantly higher in idiopathic asthenozoospermia and idiopathic oligozoospermia than that in obstructive azoospermia and control group (F0.05/2(2,82) = 115.50, p 0.001). There was no significant difference in oligomer expression between different groups, but 20% of idiopathic asthenozoospermia cases showed a decrease.Significantly different OT baseline concentrations and OTR expressions between fertile and infertile men strongly suggest that OT/OTR system is likely to be linked with male infertility, providing new insights into the pathogenesis and treatment of male infertility.

Background It remains unclear whether conservative treatment should be used to treat the common undisplaced femoral neck fractures that develop in the elderly. Herein, we systematically review the rates of union and avascular necrosis after conservative and surgical treatment of undisplaced femoral neck fractures. Methods We searched the EMBASE, PubMed, OVID, Cochrane Library, Web of Science, and Scopus databases for randomized controlled trials or observational studies that assessed the outcomes of conservative or surgical treatments of undisplaced femoral neck fractures. No language or publication year limitation was imposed. Statistical analyses were performed with the aid of the chi-squared test. We evaluated the quality of each publication and the risk of bias. Results Twenty-nine studies involving 5071 patients were ultimately included; 1120 patients were treated conservatively and 3951 surgically. The union rates were 68.8% (642/933) and 92.6% (635/686) in the former and latter groups, respectively (p