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Lan Sun,1 Hong-Juan Yao,2 Jing-Cao Li,1 Bao-Quan Zhao,1 Yong-An Wang,1 Ying-Ge Zhang1 1Key Laboratory of Nanopharmacology and Nanotoxicology, Beijing Institute of Pharmacology and Toxicology, Beijing, People’s Republic of China; 2Key Laboratory of Antibiotic Bioengineering of National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology (IMB), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, People’s Republic of ChinaCorrespondence: Ying-Ge Zhang; Yong-An Wang, Beijing Institute of Pharmacology and Toxicology, Beijing, People’s Republic of China, Tel +86 10-66930654 ; +86 10-66874607, Fax +86 10-68211656, Email Zhangyg58@126.com; yonganw@126.comIntroduction: Hepatocellular cancer stem cells (CSCs) play crucial roles in hepatocellular cancer initiation, development, relapse, and metastasis. Therefore, eradication of this cell population is a primary objective in hepatocellular cancer therapy. We prepared a nanodrug delivery system with activated carbon nanoparticles (ACNP) as carriers and metformin (MET) as drug (ACNP-MET), which was able to selectively eliminate hepatocellular CSCs and thereby increase the effects of MET on hepatocellular cancers.Methods: ACNP were prepared by ball milling and deposition in distilled water. Suspension of ACNP and MET was mixed and the best ratio of ACNP and MET was determined based on the isothermal adsorption formula. Hepatocellular CSCs were identified as CD133+ cells and cultured in serum-free medium. We investigated the effects of ACNP-MET on hepatocellular CSCs, including the inhibitory effects, the targeting efficiency, self-renewal capacity, and the sphere-forming capacity of hepatocellular CSCs. Next, we evaluated the therapeutic efficacy of ACNP-MET by using in vivo relapsed tumor models of hepatocellular CSCs.Results: The ACNP have a similar size, a regular spherical shape and a smooth surface. The optimal ratio for adsorption was MET: ACNP=1:4. ACNP-MET could target and inhibit the proliferation of CD133+ population and decrease mammosphere formation and renewal of CD133+ population in vitro and in vivo.Conclusion: These results not only suggest that nanodrug delivery system increased the effects of MET, but also shed light on the mechanisms of the therapeutic effects of MET and ACNP-MET on hepatocellular cancers. ACNP, as a good nano-carrier, could strengthen the effect of MET by carrying drugs to the micro-environment of hepatocellular CSCs.Keywords: nanodrug delivery system, metformin, CD133, hepatocellular cancer stem cells

Hao Dong,1,* Yan-Qiang Qin,2,* Ying-Chun Sun,2,* Hai-Jiang Yao,2 Xian-Kuan Cheng,2 Yan Yu,1 Shou-Si Lu1 1Beijing Bo’ai Hospital, China Rehabilitation Research Center, China Rehabilitation Science Institute, Beijing, People’s Republic of China; 2Treatment Center of TCM, Beijing Bo’ai Hospital, China Rehabilitation Research Center, China Rehabilitation Science Institute, School of Rehabilitation Medicine, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan-Qiang Qin; Ying-Chun SunTreatment Center of TCM, Beijing Bo’ai Hospital, China Rehabilitation Research Center, China Rehabilitation Science Institute, No. 10 Jiaomen North Road, Beijing, 100068, People’s Republic of ChinaTel +86 18612251241Email yanqiangqin@126.com; syccrrc@sina.comBackground: Electroacupuncture (EA) is a form of physical therapy that has been widely used in clinical practice in China. Post-stroke depression (PSD) is the most common neuropsychiatric complication after stroke. EA has been shown to have beneficial effects on PSD patients. However, the potential mechanism underlying the protective effects of EA on PSD remains unclear. Here, we investigated whether tissue plasminogen activator (tPA)/brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling pathway participates in the therapeutic effects of EA in a rat PSD model.Methods: Experimental PSD was induced by combining middle cerebral artery occlusion (MCAO) with chronic unpredictable mild stimulation (CUMS) in adult male rats. Bodyweight gain, neurological score, sucrose preference, and open field test were determined at 0, 7, 14, and 35 days after completing MCAO. The protein expressions of tPA, precursor BDNF (proBDNF), mature BDNF (mBDNF), and TrkB were measured by immunofluorescence and Western blot analysis. The tPA inhibitor plasminogen inhibitor-1 (PAI-1) was used to explore whether tPA plays a crucial role in the protective effects of EA on PSD.Results: Compared with the sham rats, the PSD rats showed decreased bodyweight, deteriorated neurological score, and significant depressive-like behaviors. EA remarkably reversed bodyweight loss, neurological deficit, and depressive-like behaviors in PSD rats. Immunofluorescence staining and Western blot analysis showed that PSD-induced decreased expression of tPA, mBDNF, and TrkB were prevented by EA. Furthermore, we found that the effects of EA against PSD-induced depressive-like behaviors were abolished by PAI-1, the specific inhibitor of tPA.Conclusion: Our results suggest that the improvement in depressive-like behaviors induced by EA is likely achieved via activation of the tPA/BDNF/TrkB pathway.Keywords: electroacupuncture, poststroke depression, depressive-like behaviors, tPA/BDNF/TrkB, chronic unpredictable mild stimulation

Ying Men*, Xiao-Xing Wang*, Ruo-Jing Li, Yan Zhang, Wei Tian, Hong-Juan Yao, Rui-Jun Ju, Xue Ying, Jia Zhou, Nan Li, Liang Zhang, Yang Yu, Wan-Liang LuState Key Laboratory of Natural and Biomimetic Drugs, and School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China*These authors contributed equally to this manuscriptBackground: Multidrug resistance (MDR) of cancers can be circumvented by inducing programmed cell death, which is known as apoptosis. Mitochondria play a crucial role in apoptosis. Mitochondria-specific therapy would provide an efficient strategy for treating resistant cancers.Design and methods: A strategy was proposed here to overcome MDR by designing cancer mitochondria-specific drug-loaded liposomes, namely, antiresistant epirubicin mitosomes, aimed at treating resistant leukemia by targeting mitochondria. Evaluations were performed on human chronic leukemia K562, MDR K562/ADR cells, and female BALB/c nude mice xenografted with MDR K562/ADR cells. The liposomes were characterized through assays of cytotoxicity, mitochondrial targeting, caspase-9 and caspase-3, antitumor activities, and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) analysis.Results: The average size of antiresistant epirubicin mitosomes was in the range of 105–115 nm. Antiresistant epirubicin mitosomes were effective in inhibiting proliferation of MDR K562/ADR cells in vitro and selectively accumulated into the mitochondria. Caspase-9 and caspase-3 activity was increased after applying antiresistant epirubicin mitosomes. In xenografted resistant MDR K562/ADR tumor in nude mice, antiresistant tumor effect of antiresistant epirubicin mitosomes was evidently observed. Apoptotic inducing effects by antiresistant epirubicin mitosomes were noticeably evidenced via mitochondrial pathway.Conclusions: Antiresistant epirubicin mitosomes had significant inhibitory effect against resistant leukemia in vitro and in vivo, hence providing a promising strategy for improving therapeutic efficacy in resistant human leukemia.Keywords: mitosomes, mitochondria signaling pathway, nude mice

Objective: To investigate the clinical effect of pulsed thulium laser (PTL) combined with triamcinolone acetonide injection in the treatment of failed posterior urethral anastomosis (FPUA)., Methods: This retrospective study included 35 male patients treated in Gongli Hospital for failed posterior urethral anastomosis from January 2018 to December 2023. All the patients underwent direct-vision internal urethrotomy (DVIU) with transurethral PTL (the PTL group, n = 15) or transurethral plasma (the TUP group, n = 20), and all received intralesional injection of triamcinolone acetonide. We followed up the patients for a median of 21 months, recorded the age, length of urethral stricture, operation time, pre- and post-operative maximum urinary flow rate (Qmax), postoperative complications and recurrence of urethral stricture, and compared the data obtained between the two groups., Results: All the patients smoothly completed the treatment procedures. No statistically significant differences were observed in the age, length of urethral stricture, operation time and postoperative complications between the two groups (P > 0.05). The median follow-up time for the thulium laser group and plasma group was 21.0 months (IQR 16.0－24.0) and 21.0 months (IQR 17.0－25.0), respectively, with a statistically significant difference observed in the maximum urine flow rate before and after surgery at the 12-month mark (P < 0.01). No significant disparity was found in terms of relapse-free survival between the two groups (P = 0.398) Conclusion: Pulsed thulium laser combined with triamcinolone acetonide injection can effectively maintain a short-term cicatricial stability of the urethral stricture and satisfactory urethral patency, obviously superior to plasmotomy as a remedial treatment of urethral stricture after failed posterior urethral anastomosis.

Human DNA topoisomerase 1 (Top1) is a crucial enzyme responsible for alleviating torsional stress on DNA during transcription and replication, thereby maintaining genome stability. Previous researches had found that non-working Top1 interacted extensively with chromosomal DNA in human cells. However, the reason for its retention on chromosomal DNA remained unclear. In this study, we discovered a close association between Top1 and chromosomal DNA, specifically linked to the presence of G-quadruplex (G4) structures. G4 structures, formed during transcription, trap Top1 and hinder its ability to relax neighboring DNAs. Disruption of the Top1-G4 interaction using G4 ligand relieved the inhibitory effect of G4 on Top1 activity, resulting in a further reduction of R-loop levels in cells. Additionally, the activation of Top1 through the use of a G4 ligand enhanced the toxicity of Top1 inhibitors towards cancer cells. Our study uncovers a negative regulation mechanism of human Top1 and highlights a novel pathway for activating Top1., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Recurrence and extraocular metastasis in advanced intraocular retinoblastoma (RB) are still major obstacles for successful treatment of Chinese children. Tuberous sclerosis complex (TSC) is a very rare, multisystemic genetic disorder characterized by hamartomatous growth. In this study, we aimed to compare genomic and epigenomic profiles with human RB or TSC using recently developed nanopore sequencing, and to identify disease-associated variations or genes. Peripheral blood samples were collected from either RB or RB/TSC patients plus their normal siblings, followed by nanopore sequencing and identification of disease-specific structural variations (SVs) and differentially methylated regions (DMRs) by a systematic biology strategy named as multiomics-based joint screening framework. In total, 316 RB- and 1295 TSC-unique SVs were identified, as well as 1072 RB- and 1114 TSC-associated DMRs, respectively. We eventually identified 6 key genes for RB for further functional validation. Knockdown of CDK19 with specific siRNAs significantly inhibited Y79 cellular proliferation and increased sensitivity to carboplatin, whereas downregulation of AHNAK2 promoted the cell growth as well as drug resistance. Those two genes might serve as potential diagnostic markers or therapeutic targets of RB. The systematic biology strategy combined with functional validation might be an effective approach for rare pediatric malignances with limited samples and challenging collection process., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Long-segment lichen sclerosus (LS) urethral stricture is a challenge for urologists. Limited data are available for surgeons to make a surgical decision between Kulkarni and Asopa urethroplasty. In this retrospective study, we investigated the outcomes of these two procedures in patients with LS urethral stricture. Between January 2015 and December 2020, 77 patients with LS urethral stricture underwent Kulkarni and Asopa procedures for urethroplasty in the Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (Shanghai, China). Of the 77 patients, 42 (54.5%) underwent the Asopa procedure and 35 (45.5%) underwent the Kulkarni procedure. The overall complication rate was 34.2% in the Kulkarni group and 19.0% in the Asopa group, and no difference was observed ( P = 0.105). Among the complications, no statistical difference was observed in the incidence of urethral stricture recurrence ( P = 0.724) or glans dehiscence ( P = 0.246) except for postoperative meatus stenosis ( P = 0.020). However, the recurrence-free survival rate between the two procedures was significantly different ( P = 0.016). Cox survival analysis showed that antiplatelet/anticoagulant therapy use ( P = 0.020), diabetes ( P = 0.003), current/former smoking ( P = 0.019), coronary heart disease ( P < 0.001), and stricture length ( P = 0.028) may lead to a higher hazard ratio of complications. Even so, these two techniques can still provide acceptable results with their own advantages in the surgical treatment of LS urethral strictures. The surgical alternative should be considered comprehensively according to the patient characteristics and surgeon preferences. Moreover, our results showed that antiplatelet/anticoagulant therapy use, diabetes, coronary heart disease, current/former smoking, and stricture length may be contributing factors of complications. Therefore, patients with LS are advised to undergo early interventions for better therapeutic effects., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Objective: To observe the effect of electroacupuncture(EA) on activities of A2 type astrocytes(A2s)and A1 type astrocytes (A1s) , expressions of neurofilament protein 200 (NF-200, a marker of axon regeneration), nexin 1(NL1, a marker of synaptic regeneration), and regeneration of Nissl bodies in rats with spinal cord injury (SCI), so as to explore its mechanisms underlying improvement of SCI., Methods: A total of 75 male SD rats were rando-mized into sham operation, model, antibody neutralizing (AN), EA and EA+AN groups, with 15 rats in each group. The SCI model was established by using an infinite field impactor to deliver an about 200 k dyne weight onto the exposed spinal cord after making a dorsal laminectomy at vertebral level T10. EA (2 Hz, 1 mA) was applied to"Dazhui"(GV14) and "Mingmen"(GV4) for 20 min, once daily for 28 days. After modeling, intraspinal injection of neutralizing antibodies IL-1α, TNF-α and complement 1q (C1q, 2 μL) to the injured spinal locus for inhibition of A1 type astrocytes (A1s) was conducted on the 1 st , 7 th , 14 th and 21 st day for rats of AN and EA+AN groups. BBB rating scale was used to evaluate hindlimb locomotor function on day 1, 7, 14, 21 and 28 after modeling. The activation of A2s (its specific marker S100a10), astrocyte (its specific marker glial fibrillary acidic protein, GFAP), and A1s (its specific marker C3) in the spinal cord was detected by immunofluorescence, and the protein expressions of NF-200 and NL1 in the spinal cord detected by Western blot and immunohistochemistry, separately, and the neuronal regeneration was observed after Nissl staining., Results: After SCI, the BBB scores at 1 , 7, 14, 21 and 28 day, and the immunoactivity of NL1 and NF-200 were significantly decreased ( P <0.01), and the fluorescence intensity of double labelled S100a10 (A2s)/GFAP and C3, and the expression of NF-200 were considerably increased in the model group ( P <0.05, P <0.01). In contrast to the model group, the BBB scores at 7, 14, 21 and 28 day, and the immunoactivity of NL1 and NF-200, and the fluorescence intensity of A2s/GFAP in the AN, EA and AN+EA groups, and the expressions of NL1 in the EA and AN+EA groups, and expression of NF-200 protein in the AN+EA group were evidently increased ( P <0.05, P <0.01), and the fluorescence intensity of C3 was strikingly decreased in the EA group ( P <0.01). The effect of AN+EA was significantly superior to that of single AN and EA in increasing BBB scores at 14, 21 and 28 day, and in up-regulating the immunoactivity of NF-200( P <0.01, P <0.05). Nissl staining showed damaged structure of the gray matter of the spinal cord, atrophy of the Nissl body, and pyknosis of neurons, which was milder in the AN and EA groups, particularly in the AN+EA group., Conclusion: EA at GV14 and GV4 may promote activation of A2s and promote regeneration of axons and synapses in SCI model rats.

Background: Silver sulfadiazine is commonly used to treat local burn wounds. Aquacel-Ag is a hydrogen fiber dressing containing ionic silver that reduces burn wound infection and promotes antimicrobial activity. It is necessary to compare the efficacy of the two in the healing of burns., Aims: The aim of this study was to systematically evaluate the effect of Aquacel-Ag on burn wound healing., Methods: A computerized search of CNKI, VIP, Wanfang, SinoMed, PubMed, Cochrane Library, EMbase, Science Direct, Web of Science, Wiley Online Library, and Open Access Library databases was performed from January 1, 2000 to December 31, 2021 for randomized controlled clinical trials. The trials on Aquacel-Ag dressing and silver sulfadiazine in the treatment of burns were selected. Meta-analysis was performed using Review Manager 5.0 software., Results: Eleven articles were finally included, with 794 burn patients. Meta-analysis results showed that compared with patients treated with silver sulfadiazine, burn patients treated with Aquacel-Ag dressing had shorter wound healing time [MD = -2.49, 95% CI (-5.64-0.65), p = 0.12], significantly lower tumor necrosis factor-α (TNF-α) level [MD = -0.52, 95% CI (-0.82-0.22), p = 0.0008], higher wound healing rate [MD = 8.41, 95% CI (3.39-13.43), p = 0.001], fewer dressing changes [MD = -3.27, 95% CI (-4.90-1.63), p < 0.0001]., Conclusion: Aquacel-Ag dressing can shorten wound healing time and effectively reduce inflammatory reactions in burn patients compared with silver sulfadiazine, but their safety still needs further exploration and analysis., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Objective: To investigate the clinical efficacy of electrophysiological appropriateness technique (EAT) therapy based on the traditional Chinese medicine (TCM) meridian theory in managing postoperative pain after urethral reconstruction surgery., Methods: Using the real-world study approach, we enrolled 61 male patients undergoing urethral reconstruction and divided them into a control group (n = 30) and an observation group (n = 31), the former receiving patient-controlled intravenous analgesia (PCIA), while the latter PCIA plus EAT at 4 pairs of acupoints (Hegu, Neiguan, Zusanli and Sanyinjiao bilaterally) and the Ashi point, with 100 mg tramadol hydrochloride given orally as remedial analgesia in both groups in case of postoperative Visual Analogue Scale (VAS) score ≥4. We compared the VAS scores at 4, 12, 24 and 48 hours postoperatively, the dose of cumulative fentanyl used at 48 hours, the number of cases needing remedial analgesia, the time to first flatus and the incidence of adverse reactions between the two groups of patients., Results: The VAS scores were markedly lower in the observation than in the control group at 4, 12, 24 and 48 hours after surgery (P < 0.05), with statistically significant differences in time-dependent effect and interactive effect (P < 0.05). Significant reduction was observed in the doses of cumulative fentanyl (P < 0.05) and remedial tramadol analgesia (P < 0.05), time to first flatus (P < 0.05), and incidence of adverse reactions (P < 0.05) in the observation group in comparison with the controls., Conclusion: Electrophysiological therapy based on the TCM meridian theory can safely and effectively alleviate postoperative pain after urethral reconstruction, reduce opioid consumption, and decrease adverse events.

Cardiovascular complications of patients with type 2 diabetes mellitus (T2DM) threaten the health and life of numerous individuals. Recently, growth factor receptor-binding protein 10 (GRB10) was found to play a pivotal role in vascular complications of T2DM, which participates in the regulation of lipid metabolism of T2DM patients. The genetic variation of GRB10 rs1800504 is closely related to the risk of coronary heart disease in patients with T2DM. The development of GRB10 as a key mediator in the association of lipid metabolism with cardiovascular complications in T2DM is detailed in and may provide new potential concerns for the study of cardiovascular complications in T2DM patients., Competing Interests: Conflict-of-interest statement: All authors declare that there are no conflicts of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: The aim of this study was to describe the clinical and procedural risk factors associated with the unplanned neurosurgical intensive care unit (NICU) readmission of patients after elective supratentorial brain tumor resection and serves as an exploratory analysis toward the development of a risk stratification tool that may be prospectively applied to this patient population., Methods: This was a retrospective observational cohort study. The electronic medical records of patients admitted to an institutional NICU between September 2018 and November 2021 after elective supratentorial brain tumor resection were reviewed. Demographic and perioperative clinical factors were recorded. A prognostic model was derived from the data of 4892 patients recruited between September 2018 and May 2021 (development cohort). A nomogram was created to display these predictor variables and their corresponding points and risks of readmission. External validation was evaluated using a series of 1118 patients recruited between June 2021 and November 2021 (validation cohort). Finally, a decision curve analysis was performed to determine the clinical usefulness of the prognostic model., Results: Of the 4892 patients in the development cohort, 220 (4.5%) had an unplanned NICU readmission. Older age, lesion type, Karnofsky Performance Status (KPS) < 70 at admission, longer duration of surgery, retention of endotracheal intubation on NICU entry, and longer NICU length of stay (LOS) after surgery were independently associated with an unplanned NICU readmission. A total of 1118 patients recruited between June 2021 and November 2021 were included for external validation, and the model's discrimination remained acceptable (C-statistic = 0.744, 95% CI 0.675-0.814). The decision curve analysis for the prognostic model in the development and validation cohorts showed that at a threshold probability between 0.05 and 0.8, the prognostic model showed a positive net benefit., Conclusions: A predictive model that included age, lesion type, KPS < 70 at admission, duration of surgery, retention of endotracheal intubation on NICU entry, and NICU LOS after surgery had an acceptable ability to identify elective supratentorial brain tumor resection patients at high risk for an unplanned NICU readmission. These risk factors and this prediction model may facilitate better resource allocation in the NICU and improve patient outcomes.

Background: Decompressive craniectomy (DC) and intracranial pressure (ICP) monitoring are common approaches to reduce the death rate of Traumatic brain injury (TBI) patients, but the outcomes of these patients are unfavorable, particularly those who receive bilateral DC. The authors discuss their experience using ICP and other potential methods to improve the outcomes of TBI patients who receive bilateral DC., Methods: Data from TBI patients receiving bilateral DC from Jan. 2008 to Jan. 2022 were collected via a retrospective chart review. Included patients who received unplanned contralateral DC after initial surgery were identified as unplanned secondary surgery (USS) patients. Patients' demographics and baseline medical status; pre-, intra-, and postoperative events; and follow-up visit outcome data were analyzed., Results: A total of 151 TBI patients were included. Patients who underwent USS experienced more severe outcomes as assessed using the 3-month modified Rankin Scale score (P = 0.024). In bilateral DC TBI patients, USS were associated with worsen outcomes, moreover, ICP monitoring was able to lower their death rate and was associated with a lower USS incidence. In USS patients, ICP monitoring was not associated with improved outcomes but was able to lower their mortality rate (2/19, 10.5%, vs. 10/25, 40.0%; P = 0.042)., Conclusion: The avoidance of USS may be associated with improved outcomes of TBI patients who underwent bilateral DC. ICP monitoring was a potential approach to lower USS rate in TBI patients, but its specific benefits were uncertain., (© 2022. The Author(s).)

Background: Our aim of this study was to identify risk factors and develop a prediction model for unplanned neurological intensive care unit (NICU) events after elective infratentorial brain tumor resection in order to propose an individualized admission to the NICU tailored to patient needs., Methods: Patients admitted to our NICU between September 2018 and May 2021 after elective infratentorial brain tumor resection were reviewed. Prolonged NICU stays and unplanned NICU admissions were defined as unplanned NICU events. The prognostic model of unplanned NICU events was developed using a forward stepwise logistic regression analysis, and external validation was evaluated. The C-statistic was used to assess discrimination, and a smooth, nonparametric calibration line was used to assess calibration graphically in the model., Results: Of the 1,710 patients in the development cohort, unplanned NICU events occurred in 162 (9.5%). Based on the lesion type, a Karnofsky Performance Status score <70 at admission, longer duration of surgery, bleeding in the operative area evident on postoperative computed tomography, higher fibrinogen and blood glucose levels at admission, and more intraoperative blood loss were independently associated with unplanned NICU events. The external validation test showed good discrimination (C-statistic = 0.811) and calibration (Hosmer-Lemeshow P = 0.141) for unplanned NICU events., Conclusions: Several patient and operative characteristics are associated with a greater likelihood of the occurrence of unplanned NICU events. In the future, we may be able to provide better help for the resource allocation of NICUs according to these risk factors and prediction models., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Numerous epidemiological studies have shown a close relationship between outdoor air pollution and increased risks for cancer, infection, and cardiopulmonary diseases. However, very few studies have investigated the potential health effects of coexposure to airborne particulate matter (PM) and bioaerosols through the transmission of infectious agents, particularly under the current circumstances of the coronavirus disease 2019 pandemic. In this study, we aimed to identify urinary metabolite biomarkers that might serve as clinically predictive or diagnostic standards for relevant diseases in a real-time manner. We performed an unbiased gas/liquid chromatography-mass spectroscopy (GC/LC-MS) approach to detect urinary metabolites in 92 samples from young healthy individuals collected at three different time points after exposure to clean air, polluted ambient, or purified air, as well as two additional time points after air repollution or repurification. Subsequently, we compared the metabolomic profiles between the two time points using an integrated analysis, along with Kyoto Encyclopedia of Genes and Genomes-enriched pathway and time-series analysis. We identified 33 and 155 differential metabolites (DMs) associated with PM and bioaerosol exposure using GC/LC-MS and follow-up analyses, respectively. Our findings suggest that 16-dehydroprogesterone and 4-hydroxyphenylethanol in urine samples may serve as potential biomarkers to predict or diagnose PM- or bioaerosol-related diseases, respectively. The results indicated apparent differences between PM- and bioaerosol-associated DMs at five different time points and revealed dynamic alterations in the urinary metabolic profiles of young healthy humans with cyclic exposure to clean and polluted air environments. Our findings will help in investigating the detrimental health effects of short-term coexposure to airborne PM and bioaerosols in a real-time manner and improve clinically predictive or diagnostic strategies for preventing air pollution-related diseases., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Artificial urethral sphincter (AUS) implantation is the definitive management of male stress urinary incontinence (SUI). Under the long-term pressure of the cuff, recurrence of incontinence caused by urethral atrophy can always be observed in patients. In this situation, distal cuff locations are needed, and new cuff sites should be sought in patients who need to undergo AUS reimplantations. Meanwhile, the circumference of the more distal urethra is often too small to fit with a 4.0 cm cuff. This means that the bulk of the urethra should be added not only for a sufficient urethral circumference but also for better protection. Here, we report a case that required AUS reimplantation because of urethral atrophy. This 73-year-old man had undergone AUS implantation 7 years ago and developed incontinence in the past 3 months. Physical examination and ultrasonography determined that the device still worked, and no obstruction or injury was observed through cystoscopy. Surgery for revision of the AUS was needed. In this operation, a new cuff was implanted transcorporally, which was 2 to 3 cm distal to the original cuff site. During a 6 month short-term follow-up, no stress incontinence, urethral injury, or dysuria was observed. The transcorporal technique offers significant advantages in patients with urethral atrophy: corporal tunica albuginea is added to the urethra, allowing a suitable cuff size and lower risk of erosion. It is worth recommending in the reoperation of AUS implantation.

Background: This study describes and compares three surgical procedures for the construction of urethral stricture (US) models in rabbits., Methods: Forty adult male rabbits were allocated to four groups: 36 rabbits were randomly assigned to three experimental groups, while the remaining 4 were assigned to a sham group. The penis was separated from the rectum. Then along the ventral midline, a longitudinal penile skin incision was made while ensuring that the urethral mucosa was intact and the muscular layer was not completely incised. In group 1 (n=12), ventral semi-circumferential mucosa electrocoagulation of a 1-cm length of the anterior urethra was performed until ulceration occurred. In group 2 (n=12), the ventral urethral mucosa was incised, and electrocoagulation of the dorsal semi-circumferential mucosa was performed. In group 3 (n=12), whole-circumferential mucosa electrocoagulation was performed. In group 4 (n=4), no special treatment was performed. Four weeks later, urethrography, urethroscopy, and histological evaluation were carried out., Results: The weights of the rabbits in the four groups were comparable. There was no significant difference between groups 2 and 3 with regard to operative time, but the operative time in these groups was significantly longer than that in group 1 (group 2 vs. group 1: P<0.05, group 3 vs. group 1: P<0.001). After the surgery, urinary fistula with infection occurred in one rabbit in group 1, and one rabbit died due to urethral atresia in group 3. According to the urethrography and urethroscopy findings, 9 out of 12 rabbits in group 1, 5 out of 12 rabbits in group 2, and 11 out of 11 rabbits in group 3 developed US, while no rabbits in the sham group developed US. Histopathological examination revealed injury to the urothelium, inflammatory infiltration, a decrease in the amount of blood vessels and smooth muscle fibers, and a decrease in the amount of collagen fibers., Conclusions: Compared with the semi-circumferential procedures, the whole-circumferential procedure had a higher success rate. Therefore, this procedure seems to have potential for the construction of long-segment rabbit US models., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-104/coif). The authors have no conflicts of interest to declare., (2022 Translational Andrology and Urology. All rights reserved.)

Background: Extramammary Paget's disease (EMPD) is a rare malignant intraepidermal adenocarcinoma that is poorly understood. Regulatory long noncoding RNAs (lncRNAs) are characterized in many species and shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in different diseases, especially in cancer studies. In the present study, we used high-throughput sequencing to reveal the lncRNA-mRNA interaction network in extramammary Paget's disease., Methods: High-throughput sequencing was used to identify differentially expressed lncRNA and mRNA profiles between EMPD patients and healthy controls. Then, a series of bioinformatics analyses were conducted to construct the lncRNA-mRNA interaction network, which was finally confirmed in vitro., Results: Six pairs of EMPD tumor and normal skin samples were collected and sequenced to identify the differentially expressed lncRNA and mRNA profiles between EMPD and healthy controls. A total of 997 differentially expressed mRNAs and 785 differentially expressed lncRNAs were identified. The GO and KEGG analyses show that epidermal development and cell adhesion play important roles in EMPD. The results of the lncRNA-mRNA interaction network analysis suggested that NEAT1, PGAP1, FKBP5 and CDON were the pivotal nodes of the network and that lncRNA NEAT1 might regulate mRNA PGAP1, FKBP5 and CDON. The results of the quantitative real-time RT-PCR performed in ten other patients for NEAT1, PGAP1, FKBP5 and CDON were consistent with those of the sequencing analysis. Moreover, an in vitro experiment confirmed the interactions between NEAT1 and PGAP1, FKBP5 and CDON in human immortalized keratinocytes., Conclusion: These findings suggest that the lncRNA-mRNA interaction network based on four pivotal nodes, NEAT1, PGAP1 FKBP5 and CDON, may play an important role in EMPD, which will contribute to a deeper understanding of the pathogenesis of EMPD., (© 2021. The Author(s).)

Objective: To observe the curative effect of joint administration of acupuncture, western and herbal medicines and bamboo-jar-cupping in the treatment of locomotor dysfunction in patients with apoplexy (acute phase) of wind-phlegm blocking meridian-collateral type in acute stroke patients, and its influence on some relevant laboratory indexes., Methods: A total of 100 cases of acute stroke patients of wind-phlegm blocking meridian-collateral type were recruited, and equally and randomly divided into control group and treatment group according to the random number table. The patients of both groups received treatment of conventional western medicines (for anti-platelet aggregation, blood-lipid regulation, arterial plaque-stabilization, cerebral cell protection and blood pressure-lowering), Chinese herbal medicines (for promoting blood circulation to dredge the meridian-collaterals), and acupuncture of Neiguan (PC6), Chize (LU5), Zusanli (ST36), Binao (LI14) and Sanyinjiao (SP6); and in addition, the patients of the treatment group also treated by cupping with bamboo-jar (kept for 10 min). The treatment was conducted once a day for 2 weeks. After the treatment, the National Institute of Health Stroke Scale (NIHSS), Fugl-Meyer assessment (FMA), Barthel Index (BI), and traditional Chinese medicine (TCM) syndrome score were used to assess the state of neurofunction, locomotor function, daily living ability, and TCM symptoms. The contents of serum C-reactive protein, D-dimer and blood homocysteine were detected using radical immunodiffusion, immunoturbidimetry, and enzymic methods, respectively., Results: After the treatment, of the 50 and 50 cases in the control and treatment groups, 5 and 6 were cured, 7 and 18 experienced marked improvement, 23 and 20 were effective, and 15 and 6 ineffective, with the effective rate being significantly higher in the treatment group (88.0%) than in the control group (70.0%, P <0.05). Self-comparison showed that the FMA and BI scores were significantly increased ( P <0.01), and the NIHSS score and TCM syndrome score notably decreased in both groups ( P <0.01) in comparison with their own pre-treatment. Comparison between the two groups showed that the FMA and BI scores were obviously higher in the treatment group than in the control group ( P <0.05), whereas the NIHSS score and TCM syndrome score as well as the C-reaction protein content evidently lower in the treatment group than in the control group ( P <0.05, P <0.01)., Conclusion: Joint administration of acupuncture, western and Chinese herbal medicines and cupping can promote the recovery of nerve function, improve locomotor function, activities of daily living and quality of life, and reduce inflammatory state in acute stroke patients with wind-phlegm blocking collaterals.

The measurement of the energy spectrum of cosmic ray helium nuclei from 70 GeV to 80 TeV using 4.5 years of data recorded by the Dark Matter Particle Explorer (DAMPE) is reported in this work. A hardening of the spectrum is observed at an energy of about 1.3 TeV, similar to previous observations. In addition, a spectral softening at about 34 TeV is revealed for the first time with large statistics and well controlled systematic uncertainties, with an overall significance of 4.3σ. The DAMPE spectral measurements of both cosmic protons and helium nuclei suggest a particle charge dependent softening energy, although with current uncertainties a dependence on the number of nucleons cannot be ruled out.

With the development of endoscopic therapy, argon plasma coagulation (APC) has been widely used by endoscopists. It has many advantages, such as simple to operate, low cost, and minimal invasiveness. Because of its capability of lesion ablation and hemostasis, APC has several indications in the gastrointestinal tract. One of them is esophageal varices. The aim of this review is to summarize the research on APC in this field to provide a reference for clinical practice., Competing Interests: Conflict-of-interest statement: There are no potential conflicts of interest to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Rationale: Tissue engineering is a promising alternative for urethral reconstruction, and adipose-derived stem cells (ADSCs) are widely used as seeding cells. Hypoxia preconditioning can significantly enhance the therapeutic effects of ADSCs. The low oxygen tension of postoperative wound healing is inevitable and may facilitate the nutritional function of ADSCs. This study aimed to investigate if hypoxia-preconditioned ADSCs, compared to normoxia-preconditioned ADSCs, combined with scaffold could better promote urethral reconstruction and exploring the underlying mechanism., Methods: In vitro, paracrine cytokines and secretomes that were secreted by hypoxia- or normoxia-preconditioned ADSCs were added to cultures of human umbilical vein endothelial cells (HUVECs) to measure their functions. In vivo, hypoxia- or normoxia-preconditioned ADSCs were seeded on a porous nanofibrous scaffold for urethral repair on a defect model in rabbits., Results: The in vitro results showed that hypoxia could enhance the secretion of VEGFA by ADSCs, and hypoxia-preconditioned ADSCs could enhance the viability, proliferation, migration, angiogenesis, and glycolysis of HUVECs (p < 0.05). After silencing VEGFA, angiogenesis and glycolysis were significantly inhibited (p < 0.05). The in vivo results showed that compared to normoxia-preconditioned ADSCs, hypoxia-preconditioned ADSCs combined with scaffolds led to a larger urethral lumen diameter, preserved urethral morphology, and enhanced angiogenesis (p < 0.05)., Conclusions: Hypoxia preconditioning of ADSCs combined with scaffold could better promote urethral reconstruction by upregulating angiogenesis and glycolysis. Hypoxia-preconditioned ADSCs combined with novel scaffold may provide a promising alternative treatment for urethral reconstruction.

Background: Retinoblastoma (RB) is the most frequent pediatric retinal tumor. In the present study, to elucidate chemoresistance mechanisms and identify potential biomarkers in RB, we utilized RNA sequencing (RNAseq) technological platforms to reveal transcriptome profiles and identify any differentially expressed genes (DEGs) between an etoposide drug-resistant subline (Y79/EDR) and parental Y79 cells., Methods: To test whether Y79/EDR cells showed resistance to antineoplastic agents for RB, we treated the cells with etoposide, carboplatin and vincristine and analyzed them with a Cell Counting Kit-8 (CCK-8). Y79/EDR and parental Y79 cells were used for RNAseq and bioinformatics analysis to enable a genome-wide review of DEGs between the two lines using the DESeq R package (1.10.1). Then, DEG enrichment in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was analyzed with KOBAS software. Next, real-time quantitative reverse transcription polymerase chain reaction (real time QRT-PCR) and cytotoxicity assays were performed to experimentally and functionally validate the identified candidate biomarkers., Results: Y79/EDR cells showed resistance to etoposide, carboplatin and vincristine at different concentrations. In total, 524 transcripts were differentially expressed in Y79/EDR cells based on analysis of fragments per kilobase of transcript per million fragments mapped (FPKM); among these, 57 genes were downregulated and 467 genes were upregulated in Y79/EDR cells compared to parental Y79 cells. We selected candidate DEGs, including ARHGAP9, HIST1H4H, RELN, DDIT4, HK2, STC1 and PFKFB4, for mRNA expression validation with real time QRT-PCR assays and found that the expression levels determined by real time QRT-PCR were consistent with the RNAseq data. Further studies involving downregulation of ARHGAP9 with a specific siRNA showed that ARHGAP9 altered the cellular sensitivity of Y79 cells to etoposide and carboplatin., Conclusion: Our initial findings provided a genomic view of the transcription profiles of etoposide-induced acquired resistance in RB. Follow-up studies indicated that ARHGAP9 might be a chemoresistance biomarker in RB, providing insight into potential therapeutic targets for overcoming acquired chemoresistance in RB. These findings can aid in understanding and overcoming chemoresistance during treatment of RB in the clinic.

Objective: To investigate the clinical and laboratory features of Aeromonas bacteremia in patients with hematological diseases, and provide evidence for the prevention and treatment of Aeromonas infection. Methods: A retrospective study of patients with bloodstream infection of Aeromonas in our hospital from January 2014 to December 2018 was carried out. The clinical characteristics, antimicrobial susceptibility, infection seasons, antimicrobial therapy and evolution were analyzed. Results: A total of 42 patients with hematological diseases had Aeromonas bloodstream infection within 5 years. Among them, 39 cases (92.9%) of bloodstream infection occurred in the stage of neutropenia. The median time of fever was 4 (1-27) d, 22 (52.4%) patients only had fever, 6 (14.3%) with gastrointestinal symptoms (abdominal pain, diarrhea, nausea, upper gastrointestinal bleeding) , 8 (19.0%) with pulmonary infection, 13 (31.0%) with skin and soft tissue infections. Seven patients (16.7%) died with skin and soft tissue infection. The resistance of Aeromonas to carbapenems was 68.3%-70.7%, while the resistance rate to cephalosporins, quinolones and aminoglycosides were less than 10%. Conclusions: Aeromonas bacteremia in patients with hematological diseases mainly occur in the neutropenia stage, usually with symptom like fever. The mortality is increased when accompanied by skin and soft tissue infection. Antibiotic use should be based on susceptibility results, and avoid the use of carbapenems.

In this study, we investigated the genetics, clinical features, and therapeutic approach of 14 patients with 5α-reductase deficiency in China. Genotyping analysis was performed by direct sequencing of PCR products of the steroid 5α-reductase type 2 gene (SRD5A2). The 5α-reductase activities of three novel mutations were investigated by mutagenesis and an in vitro transfection assay. Most patients presented with a microphallus, variable degrees of hypospadias, and cryptorchidism. Eight of 14 patients (57.1%) were initially reared as females and changed their social gender from female to male after puberty. Nine mutations were identified in the 14 patients. p.G203S, p.Q6X, and p.R227Q were the most prevalent mutations. Three mutations (p.K35N, p.H162P, and p.Y136X) have not been reported previously. The nonsense mutation p.Y136X abolished enzymatic activity, whereas p.K35N and p.H162P retained partial enzymatic activity. Topical administration of dihydrotestosterone during infancy or early childhood combined with hypospadia repair surgery had good therapeutic results. In conclusion, we expand the mutation profile of SRD5A2 in the Chinese population. A rational clinical approach to this disorder requires early and accurate diagnosis, especially genetic diagnosis., Competing Interests: None

Background: Male genital skin loss is a common disease in urology. However, male genital skin loss accompanying a penile urethra defect is rarely reported. Herein, we describe a novel surgical technique using a composite local flap and oral mucosal graft to reconstruct the penis, which may provide a new solution for patients with similar conditions., Case Presentation: A 36-year-old male with a penile urethra defect and a large area of genital skin loss required urethral reconstruction. The meatus had descended to the penoscrotal junction. This procedure was divided into three stages. The first stage of the surgery involved burying the nude penile shaft beneath the skin of the left anteromedial thigh for coverage of the skin defect. The second stage consisted of releasing the penis and expanding the size of the urethral plate for further urethroplasty. The third stage consisted of reconstruction of the anterior urethra 6 months later. Postoperatively, the patient reported satisfactory voiding. The maximal flow rate (MFR) was 22.2 ml/s with no postvoiding residual urine at the 24-month follow-up visit. No edema, infection, hemorrhage, or cicatricial retraction were observed. The patient's erectile function was satisfactory, and his international index of erectile function-5 score (IIEF-5 score) was 23 at the 24-month follow-up visit. Additionally, the presence of nocturnal penile tumescence demonstrated that he had normal erectile function., Conclusions: This procedure is an effective surgical option for men with complete foreskin and penile urethra defects. It could also be extended as a treatment strategy when composite local or pedicle transposition flaps and free grafts are needed for specific patients.

Objective: To investigate the serum expression and influencing factors of hepcidinin patients with classical paroxysmal nocturnal hemoglobinuria (PNH) . Methods: Retrospective analysis of 36 classical PNH patients from 2016.3 to 2017.3. Serum hepcidin concentration was measured by ELISA method. The relationship between serum hepcidin concentration and erythropoiesis and iron homeostasis parameters was evaluated. Results: The median serum hepcidin level of 36 classical PNH patients was 32.03 (23.11, 118.48) μg/L, it was significantly lower than of 181.42 (106.80, 250.53) μg/L in 292 normal control subjects ( z =-5.107, P <0.001) . The median serum hepcidin of 56.41 (44.60, 95.06) μg/L in PNH patients with normal ferritin was significantly lower than that in normal controls. The median serum hepcidin concentration 23.75 (21.77, 30.35) μg/L in iron deficiency PNH patients was lower than that in the normal ferritin PNH patients. However, the median serum hepcidin level of classical PNH with elevated ferritin patients 336.19 (304.19, 375.08) μg/L was significantly higher not only than that of normal ferritin and iron deficiency PNH ones, but also than that of normal control subjects. Regression analysis showed that serum ferritin, transferrin saturation and serum albumin level were independent influencing factors of serum hepcidin level in patients with classical PNH. Conclusion: The decreased serum hepcidin level in patients with classical PNH was mainly influenced by iron metabolism factors.

The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2 1 / 2 years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Background: Previous studies have reported that physical therapy (PT) can be used for the treatment of chronic obstructive pulmonary disease (COPD). However, its effectiveness is still inconclusive. This systematic review will aim to assess its effectiveness and safety for the treatment of patients with COPD., Methods: All randomized controlled trials (RCTs) literatures of PT for COPD will be searched from the databases of Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDILINE, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Information, and Wanfang Data from inception to the present without any language restrictions. Two reviewers will independently perform the study selection, data extraction, and methodological quality assessment. A third reviewer will be invited to resolve any disagreements occurred between 2 reviewers., Results: The primary outcome is lung function. The secondary outcomes include symptoms, health-related quality of life, mortality, and adverse events. The outcome data will be pooled by using the models of random-effects or fixed-effects according to the detected heterogeneity., Conclusion: The findings of this study will provide up-todated summary evidence for assessing the effectiveness and safety of PT for COPD.

Objective: To investigate the clinical features, pathogenesis, diagnosis and scrotal reconstruction in the treatment of idiopathic scrotal calcinosis (ISC)., Methods: From March 2007 to October 2018, 10 ISC patients, aged 28－79 (mean 45) years and with a disease course of 6－497 (mean 128.4) months, were treated in our hospital. We retrospectively analyzed their clinical data and reviewed related literature., Results: All the patients underwent physical examination and biochemical and parathyroid function tests. None of them had a history of endocrine or metabolic disease, or trauma, or a family member with similar diseases, and none had subjective symptoms except local pruritus in 1 case. All were treated surgically and post-operative follow-up revealed no recurrence. Histopathological examination of the excised lesion confirmed it to be ISC., Conclusions: ISC is a rare localized benign disease, of which surgery seems an effective option for the definite diagnosis and treatment. Occasionally scrotal reconstruction may be required in case of extensive involvement of the scrotal skin.

Introduction: To present 12 cases of arterial priapism treated by superselective embolization and propose our management algorithm for this condition., Methods: Between February 2013 and May 2018, 12 cases of arterial priapism caused by blunt trauma were treated by superselective embolization. The mean age of patients was 36 years (25-47 years). All of the patients had normal sexual capability before priapism (IIEF-5 scores 24-25). All patients were treated with superselective embolization after more than 3 weeks of simple conservative treatment had failed. All cases but one used a gelatin sponge as embolic agent. A microcoil was added in one case in which the gelatin sponge failed to occlude the pseudoaneurysm. After superselective embolization, ice pack and "observation" treatments continued. The sexual capability of the patients was evaluated by IIEF-5 scores at 6 months and 12 months postoperatively., Results: The mean follow-up period was 27.2 months (13-48 months). Three patients achieved complete detumescence immediately. Nine cases needed 2-17 days to return to a flaccid nonpainful state. No patient underwent a second embolization. The time needed to improve erectile function was from 7 days to 4 months. There has been no recurrence. Eleven patients treated with gelatin sponge have normal erectile function, while one patient treated with additional microcoil embolization had mild erectile dysfunction., Conclusion: Superselective embolization of the fistula is an effective option for arterial priapism. Absorbable agents should be used. Superselective arterial embolization should be considered after 3 weeks of conservative treatment. Patients should undergo another 3 weeks of "observation" treatment before repeated intervention.

Objective: To evaluate the clinical effect of modified transobturator bulbourethral sling suspension (TBSS) in the treatment of stress urinary incontinence following radical prostatectomy., Methods: Seven male patients with stress urinary incontinence after radical prostatectomy were treated by modified TBSS in our hospital from June 2015 to June 2017 and the clinical data were analyzed retrospectively., Results: The mean operation time of the 7 cases was 60－80 minutes and the mean intra-operative blood loss was 20－40 m1. The catheter was removed on the first day after surgery, and all the incisions were healed in stage Ⅰ. During a follow-up of 6－18 months, all the 7 cases were found cured, with transient acute urinary retention in 1 case and short-term perineal pain in another as post-operative complications. At 6 months after surgery, urodynamic examinations showed no statistically significant differences from the baseline in the maximum urinary flow rate (［15.0 ± 1.6］ vs ［13.7 ± 2.1］ ml/s, P > 0.05), urine output volume (［318.6 ± 52.1］ vs ［298.6 ± 36.3］ ml, P > 0.05), and postvoid residual urine volume (［11.4 ± 9.4］ vs ［7.1 ± 5.7］ ml, P > 0.05)., Conclusions: Modified TBSS, with the advantages of less invasiveness, few complications, and low cost, is an effective option for the treatment of stress urinary incontinence after radical prostatectomy.

Introduction: Till date, there have been few reports of comparative studies on the outcomes of these different treatment modalities. In this study, we have aimed to comparatively evaluate the quality-of-life parameters, including sexual function, urinary function, and health-related quality of life (HRQOL), in patients with early stage penile cancers who underwent two different organ-sparing surgeries., Material and Methods: From March 2012 to March 2015, we enrolled 15 patients with early stage penile cancers who underwent either wide local excision or partial penectomy as organ-sparing surgical treatments. We assessed their sexual and urinary functions and their HRQOL, using the International Index of Erectile Function (IIEF-15), Self-Esteem and Relationship (SEAR), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaires and urodynamic determinations, and comparatively analyzed the outcomes of these patients who underwent either type of surgery., Results: All patients who underwent these two types of surgeries experienced satisfactory outcomes. The patients who underwent wide local excision performed relatively better, in terms of their sexual functions, urinary functions, and HRQOL, but no statistically significant differences were observed in the data collected via the IIEF-15, SEAR, EDITS, and EORTC-QLQ-C30 questionnaires and urodynamic determinations (p > 0.05), except in the data corresponding to the orgasmic function (p = 0.033)., Conclusion: Both types of organ-sparing surgeries assessed in this study achieved good outcomes, in terms of the aesthetics, sexual functions, urinary functions, and HRQOL in patients, without compromising the therapeutic effects of these surgeries. However, the observed decreases in orgasmic function will need to be addressed further., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: To investigate the diagnosis and management of penile fracture., Methods: From June 1993 to May 2017, 46 cases of penile fracture were treated in our hospital, averaging 33.5 (25－42) years of age and 3.45 (1－10) hours in duration, of which 41 occurred during sexual intercourse, 4 during masturbation and 1 during prone sleeping, 4 with hematuria, but none with dysuria or urethral bleeding. Hematoma was confined to the penis. Emergency surgical repair was performed for all the patients, 45 under spinal anesthesia and 1 under local anesthesia, 16 by coronal proximal circular incision and the other 30 by local longitudinal incision according to the rupture location on ultrasonogram. The tunica albuginea ruptures averaged 1.31 (0.5－2.5) cm in length, which were sutured in the "8" pattern for 6 cases and with the 3－0 absorbable thread for 18 cases. The skin graft or negative pressure drainage tube was routinely placed, catheters indwelt, and gauze used for early pressure dressing. In the recent few years, elastic bandages were employed for 3－5 days of pressure dressing and antibiotics administered to prevent infection. The stitches and catheter were removed at 7 days after surgery., Results: Short-term postoperative foreskin edema occurred in 14 of the 16 cases of circular degloving incision, but no postoperative complications were observed in any of the cases of local incision. Twenty-eight of the patients completed a long-term follow-up of 49.4 (10－125) months, which revealed good erectile function, painless erection, and satisfactory sexual intercourse., Conclusions: For most penile fractures, local longitudinal incision is sufficient for successful repair of the tunica albuginea, with mild injury, no influence on the blood supply or lymph reflux, and a low rate complications. It therefore is obviously advantageous over circular degloving incision except when the cavernous body of urethra is to be explored, which necessitates circular degloving incision below the coronal groove.

Objective: To introduce our experience in the treatment of arterial priapism by superselective embolization., Methods: This study included 5 cases of perineal trauma-induced arterial erectile dysfunction treated in our departmentbetween February 2011 and May 2015, all failingpreviously to respond to 3 weeks of conservative treatment. The patients were aged 25－47 (mean 35) years, with the onset of arterial priapism at 2－5 days after trauma, and all subjected to physical examination, blood gas analysis, color Doppler ultrasonography of the corpora cavernosum, and IIEF-5 scoring. All the patients underwent superselective embolization, followed by local pressing and cold compression, and IIEF-5 scores were obtained again at 6 and 12 months postoperatively., Results: All the patients had normal erectile functionbefore trauma, with a mean IIEF-5 scoreof 24.60 ± 0.55. Complete detumescenceor painless flaccidity of the penis was achieved in 1 case immediately after surgery and in the other 4 after 3－17 days of postoperative conservative treatment. None of the patients needed a second embolization and no relapse was found during a mean follow-upof 27.2 (13－48)months. The IIEF-5 scores obtained at 6 (24.00 ± 1.02) and 12 months (24.20 ± 0.82) were normal, with no statistically significant differencesfrom that before trauma., Conclusions: Selective embolization is a safe and effective option for the treatment of arterial priapism. In case of no immediate painless flaccidity of the penis after surgery, conservative treatment can be extended rather than a second operation.

Purpose: To evaluate the therapeutic effect of surgery in patients with advanced penile cancer, who have a dismal prognosis., Patients and Methods: Between September 2007 and July 2015, we treated 12 patients with surgical therapy., Results: The median follow-up period for all the patients was 16 months (range 4-60 months). The outcome and concomitant symptoms were analyzed, and the survival rates were calculated. Three of the patients are currently alive. The median overall survival of the patients was 9 months (range 4-13 months)., Conclusion: The present results suggest that surgery is a valuable treatment option for patients with advanced penile cancer. The prognosis of advanced penile cancer is closely related to lymph node and distant metastases. Flap repair can solve the problem of large area skin defect. Advanced penile cancer is difficult to treat regardless of chemotherapy or radiotherapy, and surgery cannot prolong the lives of patients. However, the dissection of lesions and repair of large area skin defects can dramatically improve the quality of life of patients, especially those with locally advanced disease without distant metastasis.

Objective: To observe the effect of electroacupuncture (EA) stimulation at "Dazhui" (GV 14) and "Mingmen" (GV 4) of the Governor Vessel at different time-points on spinal cord neuronal apoptosis and the expression of c-Jun N-terminal kinases (JNK) protein in spinal cord injury (SCI) rats, so as to reveal its mechanism underlying improving SCI., Methods: A total of 108 male SD rats were randomly divided into normal control, SCI model and EA groups which were further divided into 1, 3 and 7 d subgroups (12 rats/subgroup, 6 rats in each subgroup for TUNEL or Western blot, separately). SCI model was established by using the modified Allen's method. EA was applied to GV 14 and GV 4 for 20 min, once daily, for 1, 3 and 7 days, respectively. Basso-Beattie-Bresnahan (BBB) scale was adopted to assess the locomotor function of rats, the TUNEL method was used to examine neuronal apoptosis of injuried spinal cord, and the expression of phosphorylated (p)-c-Jun protein of T 9 -T 11 spinal cord was detected by using Western blot., Results: After modeling, the BBB scores of SCI rats on day 1, 3 and 7 were signi-ficantly decreased ( P <0.01), while the numbers of apoptotic neuronal cells and the expression levels of p-c-Jun protein in the spinal cord were considerably increased at the 3 time-points in the model group ( P <0.01, P <0.05). Following EA intervention, the decreased BBB scores on day 3 and 7, and the increased numbers of apoptotic neuronal cells on day 1, 3 and 7 and the up-regulated expression levels of p-c-Jun protein on day 3 and 7 were obviously suppressed ( P <0.05, P <0.01)., Conclusions: EA intervention can improve the locomotor function of SCI rats, which Feb be related to its effects in reducing neuronal apoptosis and down-regulating p-c-Jun protein in the injuried spinal cord.

Objective: To investigate the effect of surgery on advanced penile cancer without distant metastasis and the factors influencing the prognosis., Methods: Between September 2007 and July 2015, we treated 8 cases of advanced penile cancer without distant metastasis by penectomy and lymph node dissection. The patients were aged 37－67 (mean 51.1) years. We followed up the patients for 4－60 (mean 19.25) months postoperatively and analyzed the surgical effects and the factors affecting the prognosis., Results: Three of the patients remained alive while the other 5 (62.5%) died at 4－13 (mean 9) months after surgery. No significant complications were observed and myocutaneous flap repair showed good prognosis in 4 of the patients with largearea skin defect., Conclusions: Surgery is comparatively a valuable option for the treatment of advanced penile cancer without distant metastasis, though with a poor prognosis, and the important factor affecting its prognosis is lymph node metastasis. Flap repair can solve the problem of largearea skin defect after surgery. However, evidence is not yet sufficient to prove the effectiveness of multimodality therapy of this malignancy.

Electroacupuncture at Dazhui (GV14) and Mingmen (GV4) on the Governor Vessel has been shown to exhibit curative effects on spinal cord injury; however, the underlying mechanism remains poorly understood. In this study, we established rat models of spinal cord injury using a modified Allen's weight-drop method. Ninety-nine male Sprague-Dawley rats were randomly divided into three equal groups: sham (only laminectomy), SCI (induction of spinal cord injury at T 10 ), and EA (induction of spinal cord injury at T 10 and electroacupuncture intervention at GV14 and GV4 for 20 minutes once a day). Rats in the SCI and EA groups were further randomly divided into the following subgroups: 1-day ( n = 11), 7-day ( n = 11), and 14-day ( n = 11). At 1, 7, and 14 days after electroacupuncture treatment, the Basso, Beattie and Bresnahan locomotor rating scale showed obvious improvement in rat hind limb locomotor function, hematoxylin-eosin staining showed that the histological change of injured spinal cord tissue was obviously alleviated, and immunohistochemistry and western blot analysis showed that Wnt1, Wnt3a, β-catenin immunoreactivity and protein expression in the injured spinal cord tissue were greatly increased compared with the sham and SCI groups. These findings suggest that electroacupuncture at GV14 and GV4 upregulates Wnt1, Wnt3a, and β-catenin expression in the Wnt/β-catenin signaling pathway, exhibiting neuroprotective effects against spinal cord injury., Competing Interests: Conflicts of Interest: None declared.

Background: To identify a novel therapeutic agent for hepatocellular carcinoma (HCC), for which no promising therapeutic agent exists, we screened a panel of plants and found that Juniperus chinensis exhibited potential antiangiogenic and anti-HCC activities. We further investigated the antiangiogenic and anti-HCC effects of the active ingredient of J. chinensis extract, CBT-143-S-F6F7, both in vitro and in vivo., Methods: A tube formation assay conducted using human umbilical vein endothelial cells (HUVECs) was first performed to identify the active ingredient of CBT-143-S-F6F7. A series of angiogenesis studies, including HUVEC migration, Matrigel plug, and chorioallantoic membrane (CAM) assays, were then performed to confirm the effects of CBT-143-S-F6F7 on angiogenesis. The effects of CBT-143-S-F6F7 on tumor growth were investigated using a subcutaneous and orthotopic mouse model of HCC. In vitro studies were performed to investigate the effects of CBT-143-S-F6F7 on the cell cycle and apoptosis in HCC cells. Moreover, protein arrays for angiogenesis and apoptosis were used to discover biomarkers that may be influenced by CBT-143-S-F6F7. Finally, nuclear magnetic resonance analysis was conducted to identify the compounds of CBT-143-S-F6F7., Results: CBT-143-S-F6F7 showed significantly antiangiogenic activity in various assays, including HUVEC tube formation and migration, CAM, and Matrigel plug assays. In in vivo studies, gavage with CBT-143-S-F6F7 significantly repressed subcutaneous Huh7 tumor growth in severe combined immunodeficient (SCID) mice, and prolonged the survival of orthotopic Huh7 tumor-bearing SCID mice (a 40 % increase in median survival duration compared with the vehicle-treated mice). Immunohistochemical staining of subcutaneous Huh7 tumors in CBT-143-S-F6F7-treated mice showed a significantly decrease in the cell cycle regulatory protein cyclin D1, cellular proliferation marker Ki-67, and endothelial marker CD31. CBT-143-S-F6F7 caused arrest of the G2/M phase and induced Huh7 cell apoptosis, possibly contributing to the inhibition of HCC tumors. Protein array analysis revealed that several angiogenic and antiapoptotic factors were suppressed in CBT-143-S-F6F7-treated Huh7 cells. Finally, five compounds from CBT-143-S-F6F7 were identified., Conclusions: According to these results, we report for the first time the antiangiogenic and anti-HCC activities of CBT-143-S-F6F7, the active fractional extract of J. chinensis. We believe that CBT-143-S-F6F7 warrants further evaluation as a new anti-HCC drug.

Purpose: The main purpose of the present study was to evaluate the antiproliferative activity of bakuchiol in human gastric tumor cell line (SGC-7901) along with an effort to demonstrate its mode of action., Methods: he effect of the compound on cell viability was evaluated by MTT assay. Fluorescence and phase contrast microscopic techniques were used to study the effect of the compound on cellular morphology and apoptosis. Flow cytometry was used to assess the effect on cell cycle phase distribution., Results: The results revealed that bakuchiol exerted potent, dose-dependent as well as time-dependent growth inhibitory effects in SGC-7901 cell proliferation with IC50 values of 58.4, 42.3 and 32.5 μM at 12, 24 and 48 hrs time intervals, respectively. On treatment with 10, 50 and 100 μM dose of bakuchiol for 48 hrs, phase contrast microscope revealed that the cells got detached from one another making clusters of small number of cells floating in the medium. After the cells were treated with 10, 50 and 100 μM of bakuchiol, cells began to emit orange red fluorescence more heavily at the centre of cells indicating apoptosis. Bakuchiol also induced sub-G1 cell cycle arrest in a dose-dependent manner., Conclusion: The current findings reveal that bakuchiol is a potent cytotoxic agent against gastric cancer cells and its cytotoxicity is mediated through induction of apoptosis and sub-G1 cell cycle arrest.

The objective of this study was to compare the long-term clinical outcomes from longitudinal incisions and subcoronal circumferential degloving incisions in the surgical treatment of penile fractures. From July 2001 to July 2014, 23 patients were identified with penile fractures. Fourteen patients underwent longitudinal incisions after ultrasound localization; nine patients underwent subcoronal circumferential degloving incisions. Sexual function was evaluated preoperatively and postoperatively using an abridged International Index of Erectile Function (IIEF) questionnaire. The mean (±s.d.) operative time was 19.1 (±3.9) min in the longitudinal incision group and was 45.1 (±6.5) min in the subcoronal circumferential degloving incision group (P<0.05). The mean (±s.d.) times required to recover sexual function were 35.6 (±6.0) days in the longitudinal incision group and 54.0 (±5.8) days in the circumferential incision group (P<0.05). Six months postoperatively, the erectile functions of all cases were comparable to the level preoperatively except three patients. One patient from each group reported symptoms associated with mild ED, but they experienced satisfying sexual orgasms after psychotherapy for 2 months. Another patient's score on the IIEF-5 declined from 25 to 24 points in the circumferential incision group 10 months postoperatively, and this was associated with maintaining an erection after vaginal penetration. In conclusion, the longitudinal incision may allow quicker return to sexual function but not necessarily improved the long-term clinical outcomes. Furthermore, postoperative psychosocial nursing and psychotherapy should receive more attention.

The adhesion mediated drug resistance in cancer cells resulted from adhesion of the extracellular matrix is a major cause for multidrug resistance (MDR) and leads chemotherapeutic failure for colon cancer. In this study, we explored the role of 67-kDa laminin receptor (67LR) in chemotherapeutic drug resistance in colon cancer cells. SiRNA-mediated knockdown of 67LR decreased the cell adhesion when laminins were applied. Moreover, 67LR knockdown increased the expression of pro-apoptotic gene Bax but inhibited the expression of anti-apoptotic gene Bcl-2. Enhanced apoptosis was observed in 67LR siRNA-transfected SW480 cell when the cell was treated with doxorubicin for apoptosis induction. Furthermore, MTT assay revealed that the IC50 of chemotherapeutic toward SW480 cell adhesion to laminins was reduced after 67LR knockdown, indicating there was a significant increase of drug sensitivity in SW480 cell. In conclusion, our study demonstrated that 67LR plays a considerable role in the development of colon cancer MDR.

In an effort to explore new, noninvasive treatment options for spinal cord injuries (SCI), this study investigated the effects of electroacupuncture (EA) for SCI rat models. SCI was induced by a modified Allen's weight-drop method. We investigated the response of EA at Dazhui (GV 14) and Mingmen (GV 4) acupoints to understand the effects and mechanisms of EA in neuroprotection and neuronal function recovery after SCI. BBB testing was used to detect motor function of rats' hind limbs among groups, and EA was shown to promote the recovery of SCI rats' motor function. Nissl staining showed a restored neural morphology and an increase in the quantity of neurons after EA. Also, the antiapoptosis role was exposed by TUNEL staining. Western blotting analysis was used to determine the protein expression of neurotrophin-3 (NT-3) in spinal cord tissue. Compared to the sham group, the expression levels of NT-3 were significantly decreased and EA was shown to upregulate the expression of NT-3. The present study suggests that the role of EA in neuroprotection and dorsal neuronal function recovery after SCI in rats, especially EA stimulation at GV 14 and GV 4, can greatly promote neuronal function recovery, which may result from upregulating the expression of NT-3.

Objective: This study was to explore the effects of RNA interference mediated vascular endothelial growth factor (VEGF) gene silencing on biological behavior of renal cell carcinoma (RCC), transplanted renal tumor and angiogenesis in nude mice., Methods: The specific siRNA sequence targeting VEGF were designed and synthesized to construct hVEGF-siRNA plasmid which was transfected into RCC 786-O cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used for the detection of VEGF gene expression and western blot was adopted for the examination of VEGF protein expression. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cell growth as well as cell migration and invasion. The transplanted renal tumor models in nude mice were established, and the growth condition of nude mice, and VEGF protein expression in transplanted tumor slices and the microvessel density (MVD) were detected., Results: The expression level of VEGF mRNA in VEGF-siRNA group was significant lower than that in the control group and negative group, suggesting that establishment of plasmid specifically inhibited the expression of VEGF gene The expression level of VEGF protein in VEGF-siRNA group was significant lower than that in the control group and negative group. VEGF gene silencing has the significant inhibition effects on proliferation, migration and invasion of RCC 786-O cells. The tumor weight, VEGF protein positive rate and MVD in VEGF-siRNA group were significant lower than those in negative group and blank group., Conclusion: The VEGF gene silencing could inhibit the cell proliferation, migration and invasion of RCC 786-O cells; inhibition of VEGF protein expression could prevent transplanted RCC growth and tumor angiogenesis.

In the present study, we aimed to examine the effects of the knockdown of vascular endothelial growth factor (VEGF) by RNA interference (RNAi) on vascularization and tumor growth in renal cell carcinoma (RCC). For this purpose, a lentiviral vector expressing VEGF-shRNA was constructed and transfected into 293T cells. The efficiency of RNAi was determined by infecting human 786-O RCC cells with viral particles and measuring the VEGF mRNA levels by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The effect of transfection with VEGF‑shRNA on the secreted VEGF levels was also examined and the inhibitory effects on vascularization were also examined using a chick chorioallantoic membrane (CAM) assay. An RCC xenograft model was established in nude mice by implanting 786-O cells to form subcutaneous tumors. VEGF expression was observed by immunohistochemical (IHC) staining of the xenograft tumors. The tumor volume and tumor inhibition rate were also recorded. The apoptosis of the cancer cells was measured by TUNEL assay and the efficiency of tumor inhibition was estimated. The interference rate of VEGF‑shRNA was 72.2% in the 786-O cells. Our results revealed that VEGF mRNA expression, the secreted VEGF level in the 786-O cells and the total vessel length were markedly reduced in the VEGF‑shRNA-transfected cells compared with the controls (all P<0.05). Compared with the controls, injections of lentivirus expressing VEGF-shRNA significantly inhibited tumor growth, and reduced tumor mass and VEGF expression in the tumor tissue (all P<0.05). The apoptotic index in the treatment group was significantly higher than that in the controls (both P<0.05). Thus, our data indicate that the inhibition of VEGF expression by RNAi reduces VEGF mRNA levels, and inhibits angiogenesis and tumor growth in RCC, providing a future treatment option for RCC.

Objective: To establish a PMP-HPCE method for comparing the monosaccharides of polysaccharide in tissue-cultured and wild Dedrobium huoshanese and Dedrobium moniliforme as well as wild Dedrobium henanese, in order to investigate the similarities of their bioactive components., Methods: The PMP-monosaccharides of polysaccharide from the five investigated Dedrobium samples were separated by HPCE on a fused silica capillary column(100 cm x 50 µm) at 25 °C with 350 mmol/L BAS (adjusted to pH 10 with 1.0 mol/L NaOH) as running buffer for 34 min. The applied voltage was 20 kV and the detection wavelength was set at 250 nm., Results: Total six monosaccharides including xylose, glucose, mannose, galactose, galacturonic acid and ribose were detected in the five Dendrobiurms samples and the similarity coefficients between the ten batches of the same Dendrobium species were all above 0. 98,while remarkable dissimilarity were exhibited among species and different resources., Conclusion: PMP-HPCE technique combined with chemometrics is simple, convenient, precise, reproducible and proved to be an effective strategy for identifying the species and origins, especially in the quality assessment of Dendrobium stems.

One of the challenges in andrology nowadays is the diagnosis and treatment of external genital abnormalities and defects along with the consequent voiding, sexual, and reproductive dysfunctions, for which no guidelines are yet available. Hitherto, surgical repair and reconstruction are efficient for these diseases. The key to these operations is to individualize surgical strategies according to the specific local lesion and dysfunction, usually involving flap and graft techniques. This article presents our experience in the surgical treatment of penile and scrotal abnormalities and defects with urological and andrological techniques and microsurgical strategies, focusing on the external repair and functional reconstruction. Satisfactory treatment outcomes pivot on a precise evaluation of the disease, a rational design of surgical procedures, and an earnest communication with the patient. Some cases are rather complicated and challenging, usually with complications, and therefore deserve further researches for more effective treatment strategies in clinical practice.